Virus Fitness: Concept, Quantification, and Application to HIV Population Dynamics

  • M. E. Quiñones-Mateu
  • E. J. Arts
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 299)


Viral fitness has been broadly studied during the past three decades, mainly to test evolutionary models and population theories difficult to analyze and interpret with more complex organisms. More recent studies, however, are focused in the role of fitness on viral transmission, pathogenesis, and drug resistance. Here, we used human immunodeficiency virus (HIV) as one of the most relevant models to evaluate the importance of viral quasispecies and fitness in HIV evolution, population dynamics, disease progression, and potential clinical implications.


Virus Fitness Growth Competition Experiment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Addo MM, Altfeld M, Rosenberg ES, Eldridge RL, Philips MN, Habeeb K, Khatri A, Brander C, Robbins GK, Mazzara GP, Goulder PJ, Walker BD (2001) The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals. Proc Natl Acad Sci U S A 98:1781–1786PubMedCrossRefGoogle Scholar
  2. Aebischer T, Moskophidis D, Rohrer UH, Zinkernagel RM, Hengartner H (1991) In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 88:11047–11051PubMedGoogle Scholar
  3. Agrawal AF (2001) Sexual selection and the maintenance of sexual reproduction. Nature (London) 411:692–695PubMedCrossRefGoogle Scholar
  4. Allen TM, O’Connor DH, Jing P, Dzuris JL, Mothe BR, Vogel TU, Dunphy E, Liebl ME, Emerson C, Wilson N, Kunstman KJ, Wang X, Allison DB, Hughes AL, Desrosiers RC, Altman JD, Wolinsky SM, Sette A, Watkins DI (2000) Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature (London) 407:386–390PubMedCrossRefGoogle Scholar
  5. Altfeld M, Rosenberg ES, Shankarappa R, Mukherjee JS, Hecht FM, Eldridge RL, Addo MM, Poon SH, Phillips MN, Robbins GK, Sax PE, Boswell S, Kahn JO, Brander C, Goulder PJ, Levy JA, Mullins JI, Walker BD (2001) Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med 193:169–180PubMedCrossRefGoogle Scholar
  6. Anderson RM, May RM (1986) The invasion, persistence and spread of infectious diseases within animal and plant communities. Philos Trans R Soc Lond B Biol Sci 314:533–570PubMedGoogle Scholar
  7. Anderson RM, May RM (1992) Infectious diseases in humans: dynamics and control. Oxford University Press, OxfordGoogle Scholar
  8. Anderson RM, May RM (1996) The population biology of the interaction between HIV-1 and HIV-2: coexistence or competitive exclusion? AIDS 10:1663–1673PubMedGoogle Scholar
  9. Archer RH, Dykes C, Gerondelis P, Lloyd A, Fay P, Reichman RC, Bambara RA, Demeter LM (2000) Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. J Virol 74:8390–8401PubMedCrossRefGoogle Scholar
  10. Armand-Ugon M, Quiñones-Mateu ME, Gutierrez A, Barretina J, Blanco J, Schols D, De Clercq E, Clotet B, Este JA (2003) Reduced fitness of HIV-1 resistant to CXCR4 antagonists. Antivir Ther 8:1–8PubMedGoogle Scholar
  11. Arts EJ, Wainberg MA (1996) Mechanisms of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription. Antimicrob Agents Chemother 40:527–540PubMedGoogle Scholar
  12. Arts EJ, Quiñones-Mateu ME, Albright JL, Marois JP, Hough C, Gu Z, Wainberg MA (1998) 3′-Azido-3′-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. J Virol 72:4858–4865PubMedGoogle Scholar
  13. Asjö B, Morfeldt-Manson L, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyö EM (1986) Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet ii:660–662Google Scholar
  14. Back NK, Nijhuis M, Keulen W, Boucher CA, Oude Essink BO, van Kuilenburg AB, van Gennip AH, Berkhout B (1996) Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J 15:4040–4049PubMedGoogle Scholar
  15. Ball SC, Abraha A, Collins KR, Marozsan AJ, Baird H, Quiñones-Mateu ME, Penn-Nicholson A, Murray M, Richard N, Lobritz M, Zimmerman PA, Kawamura T, Blauvelt A, Arts EJ (2003) Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C. J Virol 77:1021–1038PubMedGoogle Scholar
  16. Barbour JD, Hecht FM, Wrin T, Segal MR, Ramstead CA, Liegler TJ, Busch MP, Petropoulos CJ, Hellmann NS, Kahn JO, Grant RM (2004) Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection. J Infect Dis 190:251–256PubMedCrossRefGoogle Scholar
  17. Barouch DH, Kunstman J, Kuroda MJ, Schmitz JE, Santra S, Peyerl FW, Krivulka GR, Beaudry K, Lifton MA, Gorgone DA, Montefiori DC, Lewis MG, Wolinsky SM, Letvin NL (2002) Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature (London) 415:335–339PubMedCrossRefGoogle Scholar
  18. Barton NH, Charlesworth B (1998) Why sex and recombination? Science 281:1986–1990PubMedCrossRefGoogle Scholar
  19. Bates M, Wrin T, Huang W, Petropoulos C, Hellmann N (2003) Practical applications of viral fitness in clinical practice. Curr Opin Infect Dis 16:11–18PubMedGoogle Scholar
  20. Berger EA, Murphy PM, Farber JM (1999) Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17:657–700PubMedCrossRefGoogle Scholar
  21. Bergstrom CT, McElhany P, Real LA (1999) Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens. Proc Natl Acad Sci USA 96:5095–5100PubMedGoogle Scholar
  22. Berkhout B (1999) HIV-1 evolution under pressure of protease inhibitors: climbing the stairs of viral fitness. J Biomed Sci 6:298–305PubMedGoogle Scholar
  23. Bjorndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, Albert J, Scarlatti G, Littman DR, Fenyo EM (1997) Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 71:7478–7487PubMedGoogle Scholar
  24. Blaak H, Brouwer M, Ran LJ, de Wolf F, Schuitemaker H (1998) In vitro replication kinetics of human immunodeficiency virus type 1 (HIV-1) variants in relation to virus load in long-term survivors of HIV-1 infection. J Infect Dis 177:600–610PubMedGoogle Scholar
  25. Blackard JT, Renjifo B, Fawzi W, Hertzmark E, Msamanga G, Mwakagile D, Hunter D, Spiegelman D, Sharghi N, Kagoma C, Essex M (2001) HIV-1 LTR subtype and perinatal transmission. Virology 287:261–265PubMedCrossRefGoogle Scholar
  26. Blauvelt A, Glushakova S, Margolis LB (2000) HIV-infected human Langerhans cells transmit infection to human lymphoid tissue ex vivo. AIDS 14:647–651PubMedCrossRefGoogle Scholar
  27. Bleiber G, Munoz M, Ciuffi A, Meylan P, Telenti A (2001) Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1. J Virol 75:3291–3300PubMedCrossRefGoogle Scholar
  28. Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ (2004) Evidence for positive epistasis in HIV-1. Science 306:1547–1550PubMedCrossRefGoogle Scholar
  29. Boots M, Sasaki A (1999) ’small worlds’ and the evolution of virulence: infection occurs locally and at a distance. Proc R Soc Lond B Biol Sci 266:1933–1938Google Scholar
  30. Borman AM, Paulous S, Clavel F (1996) Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug. J Gen Virol 77:419–426PubMedGoogle Scholar
  31. Braathen LR, Ramirez G, Kunze RO, Gelderblom H (1987) Langerhans cells as primary target cells for HIV infection. Lancet 2:1094PubMedGoogle Scholar
  32. Brambilla A, Turchetto L, Gatti A, Bovolenta C, Veglia F, Santagostino E, Gringeri A, Clementi M, Poli G, Bagnarelli P, Vicenzi E (1999) Defective nef alleles in a cohort of hemophiliacs with progressing and nonprogressing HIV-1 infection. Virology 259:349–368PubMedCrossRefGoogle Scholar
  33. Bremermann HJ, Pickering J (1983) A game-theoretical model of parasite virulence. J Theor Biol 100:411–426PubMedGoogle Scholar
  34. Buhler B, Lin YC, Morris G, Olson AJ, Wong CH, Richman DD, Elder JH, Torbett BE (2001) Viral evolution in response to the broad-based retroviral protease inhibitor TL-3. J Virol 75:9502–9508PubMedCrossRefGoogle Scholar
  35. Bull JJ (1994) Virulence. Evolution 48:1423–1437Google Scholar
  36. Burch CL, Chao L (1999) Evolution by small steps and rugged landscapes in the RNA virus phi6. Genetics 151:921–927PubMedGoogle Scholar
  37. Burch CL, Chao L (2000) Evolvability of an RNA virus is determined by its mutational neighbourhood. Nature (London) 406:625–628PubMedCrossRefGoogle Scholar
  38. Burch CL, Chao L (2004) Epistasis and its relationship to canalization in the RNA virus phi 6. Genetics 167:559–567PubMedCrossRefGoogle Scholar
  39. Burch CL, Turner PE, Hanley KA (2003) Patterns of epistasis in RNA viruses: a review of the evidence from vaccine design. J Evol Biol 16:1223–1235PubMedCrossRefGoogle Scholar
  40. Cao J, McNevin J, Holte S, Fink L, Corey L, McElrath MJ (2003) Comprehensive analysis of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-secreting CD8+ T cells in primary HIV-1 infection. J Virol 77:6867–6878PubMedCrossRefGoogle Scholar
  41. Cao Y, Qin L, Zhang L, Safrit J, Ho DD (1995) Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Eng J Med 332:201–208Google Scholar
  42. Carotenuto P, Looij D, Keldermans L, de Wolf F, Goudsmit J (1998) Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection. AIDS 12:1591–1600PubMedCrossRefGoogle Scholar
  43. Carrington M, Nelson GW, Martin MP, Kissner T, Vlahov D, Goedert JJ, Kaslow R, Buchbinder S, Hoots K, O’Brien SJ (1999) HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283:1748–1752PubMedCrossRefGoogle Scholar
  44. Cecilia D, Kulkarni SS, Tripathy SP, Gangakhedkar RR, Paranjape RS, Gadkari DA (2000) Absence of coreceptor switch with disease progression in human immunodeficiency virus infections in India. Virology 271:253–258PubMedCrossRefGoogle Scholar
  45. Chan DC, Fass D, Berger JM, Kim PS (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89:263–273PubMedCrossRefGoogle Scholar
  46. Chao L (1990) Fitness of RNA virus decreased by Muller’s ratchet [see comments]. Nature (London) 348:454–455PubMedCrossRefGoogle Scholar
  47. Cheng-Mayer C, Seto D, Tateno M, Levy JA (1988) Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80–82PubMedGoogle Scholar
  48. Chouquet C, Autran B, Gomard E, Bouley JM, Calvez V, Katlama C, Costagliola D, Riviere Y (2002) Correlation between breadth of memory HIV-specific cytotoxic T cells, viral load and disease progression in HIV infection. AIDS 16:2399–2407PubMedCrossRefGoogle Scholar
  49. Clarke DK, Duarte EA, Elena SF, Moya A, Domingo E, Holland J (1994) The red queen reigns in the kingdom of RNA viruses. Proc Natl Acad Sci U S A 91:4821–4824PubMedGoogle Scholar
  50. Clavel F, Race E, Mammano F (2000) HIV drug resistance and viral fitness. Adv Pharmacol 49:41–66PubMedGoogle Scholar
  51. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (1995) Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells [see comments]. Science 270:1811–1815PubMedGoogle Scholar
  52. Coffin JM (1986) Genetic variation in AIDS viruses. Cell 46:1–14PubMedCrossRefGoogle Scholar
  53. Coffin JM (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483–489PubMedGoogle Scholar
  54. Collins JA, Thompson MG, Paintsil E, Ricketts M, Gedzior J, Alexander L (2004) Competitive fitness of nevirapine-resistant human immunodeficiency virus type 1 mutants. J Virol 78:603–611PubMedGoogle Scholar
  55. Cooper VS, Reiskind MH, Miller JA, Shelton KA, Walther BA, Elkinton JS, Ewald PW (2002) Timing of transmission and the evolution of virulence of an insect virus. Proc R Soc Lond B Biol Sci 269:1161–1165Google Scholar
  56. Cornelissen M, Mulder-Kampinga G, Veenstra J, Zorgdrager F, Kuiken C, Hartman S, Dekker J, van Der HL, Sol C, Coutinho R (1995) Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a nonsyncytium-inducing/SI phenotypically mixed human immunodeficiency virus population. J Virol 69:1810–1818PubMedGoogle Scholar
  57. Croteau G, Doyon L, Thibeault D, McKercher G, Pilote L, Lamarre D (1997) Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. J Virol 71:1089–1096PubMedGoogle Scholar
  58. Crotty S, Cameron CE, Andino R (2001) RNA virus error catastrophe: direct molecular test by using ribavirin. Proc Natl Acad Sci U S A 98:6895–6900PubMedCrossRefGoogle Scholar
  59. Cuevas JM, Moya A, Sanjuan R (2005) Following the very initial growth of biological RNA viral clones. J Gen Virol 86:435–443PubMedCrossRefGoogle Scholar
  60. Dalod M, Dupuis M, Deschemin JC, Goujard C, Deveau C, Meyer L, Ngo N, Rouzioux C, Guillet JG, Delfraissy JF, Sinet M, Venet A (1999) Weak anti-HIV CD8(+) T-cell effector activity in HIV primary infection. J Clin Invest 104:1431–1439PubMedGoogle Scholar
  61. Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC (1992) Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene [see comments]. Science 258:1938–1941PubMedGoogle Scholar
  62. De Maria A, Moretta L (2000) HLA-class I-specific inhibitory receptors in HIV-1 infection. Hum Immunol 61:74–81PubMedGoogle Scholar
  63. De Ronde A, van Dooren M, van Der HL, Bouwhuis D, de Rooij E, van Gemen B, de Boer R, Goudsmit J (2001) Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus. J Virol 75:595–602PubMedGoogle Scholar
  64. De Visser JA, Hoekstra RF, van de Ende H (1997) Test of interaction between genetic markers that affect fitness in Aspergillus niger. Evolution 51:1499–1505Google Scholar
  65. Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellet A, Chatfield C, Lawson VA, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan JS, Cunningham A, Dwyer D, Dowton D, Mills J (1995) Genomic structure of an attenuated quasispecies of HIV-1 from a blood transfusion donor and recipients. Science 270:988–991PubMedGoogle Scholar
  66. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O’Brien SJ (1996b) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273:1856–1862PubMedGoogle Scholar
  67. Deeks SG (2001) International perspectives on antiretroviral resistance. Nonnucleoside reverse transcriptase inhibitor resistance. J Acquir Immune Defic Syndr 26Suppl 1:S25–S33PubMedGoogle Scholar
  68. Deeks SG (2003) Treatment of antiretroviral-drug-resistant HIV-1 infection. Lancet 362:2002–2011PubMedCrossRefGoogle Scholar
  69. Deeks SG, Barbour JD, Martin JN, Swanson MS, Grant RM (2000) Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis 181:946–953PubMedCrossRefGoogle Scholar
  70. Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM (2001) Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med 344:472–480PubMedCrossRefGoogle Scholar
  71. Demeter LM, Shafer RW, Meehan PM, Holden-Wiltse J, Fischl MA, Freimuth WW, Para MF, Reichman RC (2000) Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). Antimicrob Agents Chemother 44:794–797PubMedCrossRefGoogle Scholar
  72. Derdeyn CA, Decker JM, Sfakianos JN, Wu X, O’Brien WA, Ratner L, Kappes JC, Shaw GM, Hunter E (2000) Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 74:8358–8367PubMedCrossRefGoogle Scholar
  73. Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham SA, Heil ML, Kasolo F, Musonda R, Hahn BH, Shaw GM, Korber BT, Allen S, Hunter E (2004) Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022PubMedCrossRefGoogle Scholar
  74. Deval J, White KL, Miller MD, Parkin NT, Courcambeck J, Halfon P, Selmi B, Boretto J, Canard B (2004) Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. J Biol Chem 279:509–516PubMedGoogle Scholar
  75. Devereux HL, Emery VC, Johnson MA, Loveday C (2001) Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations. J Med Virol 65:218–224PubMedCrossRefGoogle Scholar
  76. Domingo E, Holland JJ (1997) RNA virusmutations and fitness for survival. Annu Rev Microbiol 51:151–178PubMedCrossRefGoogle Scholar
  77. Domingo E, Escarmís C, Sevilla N, Moya A, Elena SF, Quer J, Novella IS, Holland JJ (1996) Basic concepts in RNA virus evolution. FASEB J 10:859–864PubMedGoogle Scholar
  78. Domingo E, Menendez-Arias L, Quiñones-Mateu ME, Holguin A, Gutierrez-Rivas M, Martinez MA, Quer J, Novella IS, Holland JJ(1997) Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Prog Drug Res 48:99–128PubMedGoogle Scholar
  79. Domingo E, Escarmis C, Menendez-Arias L, Holland J (1999) Viral quasispecies and fitness variations. In: Domingo E, Webster R, Holland J (eds) Origin and evolution of viruses. Academic Press, San Diego, pp. 141–161Google Scholar
  80. Doyon L, Croteau G, Thibeault D, Poulin F, Pilote L, Lamarre D (1996) Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J Virol 70:3763–3769PubMedGoogle Scholar
  81. Duarte E, Clarke D, Moya A, Domingo E, Holland J (1992) Rapid fitness losses in mammalian RNA virus clones due to Muller’s ratchet. Proc Natl Acad Sci U S A 89:6015–6019PubMedGoogle Scholar
  82. Duarte EA, Novella IS, Weaver SC, Domingo E, Wain-Hobson S, Clarke DK, Moya A, Elena SF, de la Torre JC, Holland JJ (1994) RNA virus quasispecies: significance for viral disease and epidemiology. Infect Agents Dis 3:201–214PubMedGoogle Scholar
  83. Dueweke TJ, Pushkarskaya T, Poppe SM, Swaney SM, Zhao JQ, Chen IS, Stevenson M, Tarpley WG (1993) A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. Proc Natl Acad Sci U S A 90:4713–4717PubMedGoogle Scholar
  84. Dyer WB, Ogg GS, Demoitie MA, Jin X, Geczy AF, Rowland-Jones SL, McMichael AJ, Nixon DF, Sullivan JS (1999) Strong human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte activity in Sydney Blood Bank Cohort patients infected with nef-defective HIV type 1. J Virol 73:436–443PubMedGoogle Scholar
  85. Eastman PS, Mittler J, Kelso R, Gee C, Boyer E, Kolberg J, Urdea M, Leonard JM, Norbeck DW, Mo H, Markowitz M (1998) Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. J Virol 72:5154–5164PubMedGoogle Scholar
  86. Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS (1999) Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell 99:103–115PubMedCrossRefGoogle Scholar
  87. Elena SF (1999) Little evidence for synergism among deleterious mutations in a nonsegmented RNA virus. J Mol Evol 49:703–707PubMedCrossRefGoogle Scholar
  88. Elena SF (2001) Evolutionary history conditions the timing of transmission in vesicular stomatitis virus. Infect Genet Evol 1:151–159PubMedGoogle Scholar
  89. Elena SF, Lenski RE (1997) Test of synergistic interactions amongdeleteriousmutations in bacteria. Nature (London) 390:395–398PubMedCrossRefGoogle Scholar
  90. Elena SF, Gonzalez-Candelas F, Novella IS, Duarte EA, Clarke DK, Domingo E, Holland JJ, Moya A (1996) Evolutionoffitness in experimentalpopulationsof vesicular stomatitis virus. Genetics 142:673–679PubMedGoogle Scholar
  91. Elena SF, Sanjuan R, Borderia AV, Turner PE (2001) Transmission bottlenecks and the evolution of fitness in rapidly evolving RNA viruses. Infect Genet Evol 1:41–48PubMedGoogle Scholar
  92. Escarmis C, Davila M, Charpentier N, Bracho A, Moya A, Domingo E (1996) Genetic lesions associated with Muller’s ratchet in an RNA virus. J Mol Biol 264:255–267PubMedGoogle Scholar
  93. Escarmis C, Carrillo EC, Ferrer M, Arriaza JF, Lopez N, Tami C, Verdaguer N, Domingo E, Franze-Fernandez MT (1998) Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism. J Virol 72:10171–10179PubMedGoogle Scholar
  94. Eshel I, Feldman MW (1970) On the evolutionary effect of recombination. Theor Popul Biol 1:88–100PubMedGoogle Scholar
  95. Esnouf R, Ren J, Ross C, Jones Y, Stammers D, Stuart D (1995) Mechanism of inhibition of HIV-1 reverse transcriptase bynon-nucleoside inhibitors. Nat Struct Biol 2:303–308PubMedCrossRefGoogle Scholar
  96. Essex M (1999) Human immunodeficiency viruses in the developing world. Adv Virus Res 53:71–88PubMedGoogle Scholar
  97. Etemad-Moghadam B, Rhone D, Steenbeke T, Sun Y, Manola J, Gelman R, Fanton JW, Racz P, Tenner-Racz K, Axthelm MK, Letvin NL, Sodroski J (2002) Understanding the basis of CD4(+) T-cell depletion in macaques infected by a simian-human immunodeficiency virus. Vaccine 20:1934–1937PubMedCrossRefGoogle Scholar
  98. Evans DT, O’Connor DH, Jing P, Dzuris JL, Sidney J, da Silva J, Allen TM, Horton H, Venham JE, Rudersdorf RA, Vogel T, Pauza CD, Bontrop RE, DeMars R, Sette A, Hughes AL, Watkins DI (1999) Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nat Med 5:1270–1276PubMedGoogle Scholar
  99. Ewald PW (1993) The evolution of virulence. Sci Am 268:86–93PubMedGoogle Scholar
  100. Ewald PW (1994) Evolution of infectious diseases. Oxford University Press, New YorkGoogle Scholar
  101. Fenner F, Kessler H (1994) Evolution of the poxviruses, including the coevolution of virus and host myxomatosis. In: Morse SS (ed) The evolutionary biology of viruses. Raven Press, New York, pp 273–292Google Scholar
  102. Fenyo EM, Albert J, Asjo B (1989) Replicative capacity, cytopathic effect and cell tropism of HIV. AIDS 3Suppl 1:S5–S12PubMedGoogle Scholar
  103. Fenyo E, Schuitemaker H, Asjö B, McKeating J, Sattentau Q (2000) EC concerted action HIV variability. The history of HIV-1 biological phenotypes. Past, present and future. Review in 1997 Human Retroviruses and AIDS CompendiumGoogle Scholar
  104. Fikkert V, Van Maele B, Vercammen J, Hantson A, Van Remoortel B, Michiels M, Gurnari C, Pannecouque C, De Maeyer M, Engelborghs Y, De Clercq E, Debyser Z, Witvrouw M (2003) Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. J Virol 77:11459–11470PubMedCrossRefGoogle Scholar
  105. Froissart R, Wilke CO, Montville R, Remold SK, Chao L, Turner PE (2004) Co-infection weakens selection against epistatic mutations in RNA viruses. Genetics 168:9–19PubMedCrossRefGoogle Scholar
  106. Frost SD, Nijhuis M, Schuurman R, Boucher CA, Brown AJ (2000) Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. J Virol 74:6262–6268PubMedCrossRefGoogle Scholar
  107. Gallant JE, Gerondelis PZ, Wainberg MA, Shulman NS, Haubrich RH, St Clair M, Lanier ER, Hellmann NS, Richman DD (2003) Nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance. Antivir Ther 8:489–506PubMedGoogle Scholar
  108. Gandhi RT, Wurcel A, Rosenberg ES, Johnston MN, Hellmann N, Bates M, Hirsch MS, Walker BD (2003) Progressive reversion of human immunodeficiency virus type 1 resistance mutations in vivo after transmission of a multiply drug-resistant virus. Clin Infect Dis 37:1693–1698PubMedGoogle Scholar
  109. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM, Hahn BH (1999) Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes [see comments]. Nature (London) 397:436–441PubMedCrossRefGoogle Scholar
  110. Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, O’Brien SJ, Carrington M (2001) Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med 344:1668–1675PubMedCrossRefGoogle Scholar
  111. Garcia-Lerma JG, Gerrish PJ, Wright AC, Qari SH, Heneine W (2000) Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. J Virol 74:9339–9346PubMedCrossRefGoogle Scholar
  112. Garcia-Lerma JG, MacInnes H, Bennett D, Weinstock H, Heneine W (2004) Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. J Virol 78:7545–7552PubMedCrossRefGoogle Scholar
  113. Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG (2000) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575–585PubMedGoogle Scholar
  114. Gerondelis P, Archer RH, Palaniappan C, Reichman RC, Fay PJ, Bambara RA, Demeter LM (1999) The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5′-end-and DNA 3′-end-directed RNase H activities. J Virol 73:5803–5813PubMedGoogle Scholar
  115. Gonzalez LM, Brindeiro RM, Aguiar RS, Pereira HS, Abreu CM, Soares MA, Tanuri A (2004) Impact of nelfinavir resistance mutations on in vitro phenotype, fitness, and replication capacity of human immunodeficiency virus type 1 with subtype B and C proteases. Antimicrob Agents Chemother 48:3552–3555PubMedGoogle Scholar
  116. Goudsmit J, De Ronde A, Ho DD, Perelson AS (1996) Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase. J Virol 70:5662–5664PubMedGoogle Scholar
  117. Goudsmit J, De Ronde A, de Rooij E, de Boer R (1997) Broad spectrum of in vivo fitness of human immunodeficiency virus type 1 subpopulations differing at reverse transcriptase codons 41 and 215. J Virol 71:4479–4484PubMedGoogle Scholar
  118. Goulder PJ, Watkins DI (2004) HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 4:630–640PubMedCrossRefGoogle Scholar
  119. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgan B, Edwards A, McMichael AJ, Rowland-Jones S (1997) Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3:212–217PubMedCrossRefGoogle Scholar
  120. Goulder PJ, Altfeld MA, Rosenberg ES, Nguyen T, Tang Y, Eldridge RL, Addo MM, He S, Mukherjee JS, Phillips MN, Bunce M, Kalams SA, Sekaly RP, Walker BD, Brander C (2001) Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection. J Exp Med 193:181–194PubMedCrossRefGoogle Scholar
  121. Greenberg M, McDanal C, Stanfield-Oakley S, Jin L, Trembaly C, Sista P, Hirsch M, Matthews T (2001) Virus sensitivity to T-20 and T-1249 is independent of coreceptor usage. 8th Conference on Retroviruses and Opportunistic InfectionsGoogle Scholar
  122. Gu Z, Gao Q, Fang H, Salomon H, Parniak MA, Goldberg E, Cameron J, Wainberg MA (1994) Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2′,3′-dideoxycytidine and 2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother 38:275–281PubMedGoogle Scholar
  123. Hahn BH, Shaw GM, De Cock KM, Sharp PM (2000) AIDS as a zoonosis: scientific and public health implications. Science 287:607–614PubMedCrossRefGoogle Scholar
  124. Harrigan PR, Bloor S, Larder BA (1998) Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. J Virol 72:3773–3778PubMedGoogle Scholar
  125. Havlir DV, Eastman S, Gamst A, Richman DD (1996) Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. J Virol 70:7894–7899PubMedGoogle Scholar
  126. Hazuda DJ, Anthony NJ, Gomez RP, Jolly SM, Wai JS, Zhuang L, Fisher TE, Embrey M, Guare JP Jr, Egbertson MS, Vacca JP, Huff JR, Felock PJ, Witmer MV, Stillmock KA, Danovich R, Grobler J, Miller MD, Espeseth AS, Jin L, Chen IW, Lin JH, Kassahun K, Ellis JD, Wong BK, Xu W, Pearson PG, Schleif WA, Cortese R, Emini E, Summa V, Holloway MK, Young SD (2004a) A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc Natl Acad Sci U S A 101:11233–11238PubMedCrossRefGoogle Scholar
  127. Hazuda DJ, Young SD, Guare JP, Anthony NJ, Gomez RP, Wai JS, Vacca JP, Handt L, Motzel SL, Klein HJ, Dornadula G, Danovich RM, Witmer MV, Wilson KA, Tussey L, Schleif WA, Gabryelski LS, Jin L, Miller MD, Casimiro DR, Emini EA, Shiver JW (2004b) Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science 305:528–532PubMedCrossRefGoogle Scholar
  128. Hertogs K, de Bethune MP, Miller V, Ivens T, Schel P, Van Cauwenberge A, Van Den EC, Van Gerwen V, Azijn H, Van Houtte M, Peeters F, Staszewski S, Conant M, Bloor S, Kemp S, Larder B, Pauwels R (1998) A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 42:269–276PubMedGoogle Scholar
  129. Hirsch MS, Conway B, D’aquila RT, Johnson VA, Brun-Vezinet F, Clotet B, Demeter LM, Hammer SM, Jacobsen DM, Kuritzkes DR, Loveday C, Mellors JW, Vella S, Richman DD (1998) Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society-USA Panel. JAMA 279:1984–1991PubMedGoogle Scholar
  130. Hirsch MS, Brun-Vezinet F, D’aquila RT, Hammer SM, Johnson VA, Kuritzkes DR, Loveday C, Mellors JW, Clotet B, Conway B, Demeter LM, Vella S, Jacobsen DM, Richman DD (2000) Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel. JAMA 283:2417–2426PubMedCrossRefGoogle Scholar
  131. Hirsch VM (2004) What can natural infection of African monkeys with simian immunodeficiency virus tell us about the pathogenesis of AIDS? AIDS Rev 6:40–53PubMedGoogle Scholar
  132. Ho DD, Toyoshima T, Mo H, Kempf DJ, Norbeck D, Chen CM, Wideburg NE, Burt SK, Erickson JW, Singh MK (1994) Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor. J Virol 68:2016–2020PubMedGoogle Scholar
  133. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature (London) 373:123–126PubMedCrossRefGoogle Scholar
  134. Holland JJ, de la Torre JC, Clarke DK, Duarte E (1991) Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J Virol 65:2960–2967PubMedGoogle Scholar
  135. Holmes EC (2003) Patterns of intra-and interhost nonsynonymous variation reveal strong purifying selection in dengue virus. J Virol 77:11296–11298PubMedGoogle Scholar
  136. Holterman L, Niphuis H, Koornstra W, Dubbes R, ten Haaft P, Heeney JL (2000) The rate of progression to AIDS is independent of virus dose in simian immunodeficiency virus-infected macaques. J Gen Virol 81:1719–1726PubMedGoogle Scholar
  137. Hu DJ, Dondero TJ, Rayfield MA, George R, Schochetman G, Jaffe HW, Luo C, Kalish ML, Weniger BG, Pau C, Schable CA, Curran JW (1996) The emerging genetic diversity of HIV. The importance of global surveillance for diagnostics, research, and prevention. JAMA 275:210–216PubMedGoogle Scholar
  138. Hunt G, Tiemessen CT (2000) Occurrence of additional NF-kappaB-binding motifs in the long terminal repeat region of South African HIV type 1 subtype C isolates. AIDS Res Hum Retroviruses 16:305–306PubMedCrossRefGoogle Scholar
  139. Iglesias-Ussel MD, Casado C, Yuste E, Olivares I, Lopez-Galindez C (2002) In vitro analysis of HIV-1 resistance to nevirapine and fitness determination of resistant variants. J Gen Virol 83:93–101PubMedGoogle Scholar
  140. Imamichi T, Berg SC, Imamichi H, Lopez JC, Metcalf JA, Falloon J, Lane HC (2000) Relative replication fitness of a high-level 3′-azido-3′-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr→Gly) at codon 69. J Virol 74:10958–10964PubMedGoogle Scholar
  141. Imamichi T, Murphy MA, Imamichi H, Lane HC (2001) Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. J Virol 75:3988–3992PubMedCrossRefGoogle Scholar
  142. Joag SV (2000) Primate models of AIDS. Microbes Infect 2:223–229PubMedCrossRefGoogle Scholar
  143. Kalish ML, Baldwin A, Raktham S, Wasi C, Luo C-C, Schochetman G, Mastro TD, Young N, Vanichseni S, Rübsamen-Waigmann H, von Briesen H, Mullins JI, Delwart E, Herring B, Esparza J, Heyward WL, Osmanov S (1995) The evolving molecular epidemiology of HIV-1 envelope subtypes in injecting drug users in Bangkok, Thailand: implications for HIV vaccine trials. AIDS 9:851–857PubMedGoogle Scholar
  144. Kanki PJ, Hamel DJ, Sankale JL, Hsieh C, Thior I, Barin F, Woodcock SA, Gueye-Ndiaye A, Zhang E, Montano M, Siby T, Marlink R, NDoye I, Essex ME, Mboup S (1999) Human immunodeficiency virus type 1 subtypes differ in disease progression. J Infect Dis 179:68–73PubMedCrossRefGoogle Scholar
  145. Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ, Goedert JJ, Winkler C, O’Brien SJ, Rinaldo C, Detels R, Blattner W, Phair J, Erlich H, Mann DL (1996) Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 2:405–411PubMedCrossRefGoogle Scholar
  146. Kellam P, Larder BA (1994) Recombinant virus assay: a rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates. Antimicrob Agents Chemother 38:23–30PubMedGoogle Scholar
  147. Kelleher AD, Long C, Holmes EC, Allen RL, Wilson J, Conlon C, Workman C, Shaunak S, Olson K, Goulder P, Brander C, Ogg G, Sullivan JS, Dyer W, Jones I, McMichael AJ, Rowland-Jones S, Phillips RE (2001) Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. J Exp Med 193:375–386PubMedCrossRefGoogle Scholar
  148. Keulen W, Nijhuis M, Schuurman R, Berkhout B, Boucher C (1997) Reverse transcriptase fidelity and HIV-1 variation. Science 275:229, author reply 230–231PubMedGoogle Scholar
  149. Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, Lee JY, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson MR, Nowak MA, Shaw GM, Saag MS (1998) Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 4:1302–1307PubMedCrossRefGoogle Scholar
  150. Kimata JT, Kuller L, Anderson DB, Dailey P, Overbaugh J (1999) Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med 5:535–541PubMedGoogle Scholar
  151. Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC (1995) Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 332:228–232PubMedCrossRefGoogle Scholar
  152. Knipe DM, Howley PM (2001) Fields virology, 4th edn. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  153. Kondrashov AS (1988) Deleterious mutations and the evolution of sexual reproduction. Nature (London) 336:435–440PubMedCrossRefGoogle Scholar
  154. Kondrashov AS (1994) Muller’s ratchet under epistatic selection. Genetics 136:1469–1473PubMedGoogle Scholar
  155. Kondrashov AS, Crow JF (1991) Haploidy or diploidy: which is better? Nature (London) 351:314–315PubMedCrossRefGoogle Scholar
  156. Korber B, Hahn B, Foley B, Mellors J, Leitner T, Myers G, McCutchan F, Kuiken C (1997a) Human retroviruses and AIDS 1997. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NMGoogle Scholar
  157. Korber B, Hahn B, Foley B, Mellors JW, Leitner T, Myers G, McCutchan F, Kuiken C (1997b) Human retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences. Theoretical Biology and Byophysics Group, Los Alamos National Laboratory, Los Alamos, NMGoogle Scholar
  158. Korber B, Muldoon M, Theiler J, Gao F, Gupta R, Lapedes A, Hahn BH, Wolinsky S, Bhattacharya T (2000) Timing the ancestor of the HIV-1 pandemic strains [see comments]. Science 288:1789–1796PubMedCrossRefGoogle Scholar
  159. Kosalaraksa P, Kavlick MF, Maroun V, Le R, Mitsuya H (1999) Comparative fitness of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 (HIV-1) in an in vitro competitive HIV-1 replication assay. J Virol 73:5356–5363PubMedGoogle Scholar
  160. Kozal MJ, Shah N, Shen N, Yang R, Fucini R, Merigan TC, Richman DD, Morris D, Hubbell E, Chee M, Gingeras TR (1996) Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat Med 2:753–759PubMedCrossRefGoogle Scholar
  161. Kuiken CL, Foley B, Hahn B, Korber B, McCutchan F, Marx P, Mellors J, Mullins JI, Sodroski J, Wolinsky S (1999) Human retroviruses and AIDS 1999: a compilation and analysis of nucleic acid and amino acid sequences. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NMGoogle Scholar
  162. Kwa D, Vingerhoed J, Boeser B, Schuitemaker H (2003) Increased in vitro cytopathicity of CC chemokine receptor 5-restricted human immunodeficiency virus type 1 primary isolates correlates with a progressive clinical course of infection. J Infect Dis 187:1397–1403PubMedCrossRefGoogle Scholar
  163. Larder B (2001) Mechanisms of HIV-1 drug resistance. AIDS 15Suppl 5:S27–S34PubMedGoogle Scholar
  164. Larder BA, Kemp SD, Harrigan PR (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269:696–699PubMedGoogle Scholar
  165. Lazaro E, Escarmis C, Perez-Mercader J, Manrubia SC, Domingo E (2003) Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss. Proc Natl Acad Sci U S A 100:10830–10835PubMedCrossRefGoogle Scholar
  166. Lech WJ, Wang G, Li Yang Y, Chee Y, Dorman K, McCrae D, Lazzeroni LC, Erickson JW, Sinsheimer JS, Kaplan AH (1996) In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. J Virol 70:2038–2043PubMedGoogle Scholar
  167. Lee DJ, Robinson WE Jr (2004) Human immunodeficiency virus type 1 (HIV-1) integrase: resistance to dike to acid integrase inhibitors impairs HIV-1 replication and integration and confers cross-resistance to L-chicoric acid. J Virol 78:5835–5847PubMedGoogle Scholar
  168. Leigh-Brown AJ (1997) Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population. Proc Natl Acad Sci U S A 94:1862–1865Google Scholar
  169. Leigh Brown AJ, Frost SD, Mathews WC, Dawson K, Hellmann NS, Daar ES, Richman DD, Little SJ (2003) Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence of resistance in the antiretroviral-treated population. J Infect Dis 187:683–686PubMedCrossRefGoogle Scholar
  170. Lenski RE, May RM (1994) The evolution of virulence in parasites and pathogens: reconciliation between two competing hypotheses. J Theor Biol 169:253–265PubMedCrossRefGoogle Scholar
  171. Leroux C, Cadore JL, Montelaro RC (2004) Equine infectious anemia virus (EIAV): what has HIV’s country cousin got to tell us? Vet Res 35:485–512PubMedCrossRefGoogle Scholar
  172. Little SJ, Daar ES, D’aquila RT, Keiser PH, Connick E, Whitcomb JM, Hellmann NS, Petropoulos CJ, Sutton L, Pitt JA, Rosenberg ES, Koup RA, Walker BD, Richman DD (1999) Reduced antiretroviral drug susceptibility among patients with primary HIV infection [see comments]. JAMA 282:1142–1149PubMedCrossRefGoogle Scholar
  173. Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, Koup RA, Mellors JW, Connick E, Conway B, Kilby M, Wang L, Whitcomb JM, Hellmann NS, Richman DD (2002) Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med 347:385–394PubMedGoogle Scholar
  174. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160PubMedGoogle Scholar
  175. Loveday C (2001) International perspectives on antiretroviral resistance. Nucleoside reverse transcriptase inhibitor resistance. J Acquir Immune Defic Syndr 26Suppl 1:S10–S24PubMedGoogle Scholar
  176. Loveday C, Hill A (1995) Prediction of progression to AIDS with serum HIV-1 RNA and CD4 count. Lancet 345:790–791PubMedGoogle Scholar
  177. Lu J, Kuritzkes DR (2001) A novel recombinant marker virus assay for comparing the relative fitness of hiv-1 reverse transcriptase variants. J Acquir Immune Defic Syndr 27:7–13PubMedGoogle Scholar
  178. Lu J, Sista P, Giguel F, Greenberg M, Kuritzkes DR (2004) Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). J Virol 78:4628–4637PubMedGoogle Scholar
  179. Lukashov V, Goudsmit J (1997) Founder virus population related to route of virus transmission: a determinant of intrahost human immunodeficiency virus type 1 evolution? J Virol 71:2023–2030PubMedGoogle Scholar
  180. Maeda Y, Venzon DJ, Mitsuya H (1998) Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. J Infect Dis 177:1207–1213PubMedGoogle Scholar
  181. Mahanty S, Bray M (2004) Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 4:487–498PubMedGoogle Scholar
  182. Mammano F, Petit C, Clavel F (1998) Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 72:7632–7637PubMedGoogle Scholar
  183. Mansky LM, Temin HM (1995) Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol 69:5087–5094PubMedGoogle Scholar
  184. Margot NA, Isaacson E, McGowan I, Cheng AK, Schooley RT, Miller MD (2002) Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. AIDS 16:1227–1235PubMedGoogle Scholar
  185. Marozsan AJ, Moore D, Lobritz M, Fraundorf E, Abraha A, Reeves JD, Arts EJ (2005) Differences in the fitness of two diverse wild-type HIV-1 isolates are related to the efficiency of cell binding and entry. J Virol 79:7121–7124PubMedCrossRefGoogle Scholar
  186. Martinez-Picado J, Savara AV, Shi L, Sutton L, D’aquila RT (2000) Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. Virology 275:318–322PubMedCrossRefGoogle Scholar
  187. Martinez-Picado J, Savara AV, Sutton L, D’aquila RT (1999) Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. J Virol 73:3744–3752PubMedGoogle Scholar
  188. Martinez-Picado J, Morales-Lopetegui K, Wrin T, Garcia-Prado J, Frost SD, Petropoulos CJ, Clotet B, Ruiz L (2001) Selection of the M184V mutation during repetitive cycles of structured antiretroviral treatment interruptions. 5th International Workshop on HIV Drug Resistance and Treatment Strategies, Scottsdale, Arizona June 2001, Abstract 36Google Scholar
  189. McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ (2003) Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300:1295–1297PubMedCrossRefGoogle Scholar
  190. Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA (1996) Prognosis in HIV-1 infection predicted by the quantity of virus in plasma [see comments] [published erratum appears in Science 1997 Jan 3; 275(5296):14]. Science 272:1167–1170PubMedGoogle Scholar
  191. Menendez-Arias L, Este JA (2004) HIV-resistance to viral entry inhibitors. Curr Pharm Des 10:1845–1860PubMedCrossRefGoogle Scholar
  192. Menzo S, Castagna A, Monachetti A, Hasson H, Danise A, Carini E, Bagnarelli P, Lazzarin A, Clementi M (2004) Genotype and phenotype patterns of human immunodeficiency virus type 1 resistance to enfuvirtide during long-term treatment. Antimicrob Agents Chemother 48:3253–3259PubMedCrossRefGoogle Scholar
  193. Messenger SL, Molineux IJ, Bull JJ (1999) Virulence evolution in a virus obeys a tradeoff. Proc R Soc Lond B Biol Sci 266:397–404Google Scholar
  194. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Martino L, Hallahan CW, Selig SM, Schwartz D, Sullivan J, Connors M (2000) HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A 97:2709–2714PubMedCrossRefGoogle Scholar
  195. Miller V (2001) International perspectives on antiretroviral resistance. Resistance to protease inhibitors. J Acquir Immune Defic Syndr 26Suppl 1:S34–S50PubMedGoogle Scholar
  196. Miralles R, Moya A, Elena SF (1997) Is group selection a factor modulating the virulence of RNA viruses? Genet Res 69:165–172PubMedCrossRefGoogle Scholar
  197. Miralles R, Gerrish PJ, Moya A, Elena SF (1999a) Clonal interference and the evolution of RNA viruses. Science 285:1745–1747PubMedCrossRefGoogle Scholar
  198. Miralles R, Moya A, Elena SF (1999b) Effect of population patchiness and migration rates on the adaptation and divergence of vesicular stomatitis virus quasispecies populations. J Gen Virol 80:2051–2059PubMedGoogle Scholar
  199. Miralles R, Moya A, Elena SF (2000) Diminishing returns of population size in the rate of RNA virus adaptation. J Virol 74:3566–3571PubMedCrossRefGoogle Scholar
  200. Montefiori DC, Pantaleo G, Fink LM, Zhou JT, Zhou JY, Bilska M, Miralles GD, Fauci AS (1996) Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors. J Infect Dis 173:60–67PubMedGoogle Scholar
  201. Moore FB, Rozen DE, Lenski RE (2000) Pervasive compensatory adaptation in Escherichia coli. Proc R Soc Lond B Biol Sci 267:515–522Google Scholar
  202. Moya A, Holmes EC, Gonzalez-Candelas F (2004) The population genetics and evolutionary epidemiology of RNA viruses. Nat Rev Microbiol 2:279–288PubMedCrossRefGoogle Scholar
  203. Myint L, Matsuda M, Matsuda Z, Yokomaku Y, Chiba T, Okano A, Yamada K, Sugiura W (2004) Gag non-cleavage site mutations contribute to full recovery of viral fitness in protease inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 48:444–452PubMedCrossRefGoogle Scholar
  204. Nelson JA, Baribaud F, Edwards T, Swanstrom R (2000) Patterns of changes in human immunodeficiency virus type 1 V3 sequence populations late in infection. J Virol 74:8494–8501PubMedCrossRefGoogle Scholar
  205. Neumann T, Hagmann I, Lohrengel S, Heil ML, Derdeyn CA, Krausslich HG, Dittmar MT (2005) T20-insensitive HIV-1 from naive patients exhibits high viral fitness in a novel dual-color competition assay on primary cells. Virology 333:251–262PubMedCrossRefGoogle Scholar
  206. Newstein MC, Desrosiers RC (2001) Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. J Infect Dis 184:1262–1267PubMedCrossRefGoogle Scholar
  207. Nijhuis M, Boucher CA, Schipper P, Leitner T, Schuurman R, Albert J (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy. Proc Natl Acad Sci U S A 95:14441–14446PubMedCrossRefGoogle Scholar
  208. Nijhuis M, Schuurman R, de Jong D, Erickson J, Gustchina E, Albert J, Schipper P, Gulnik S, Boucher CA (1999) Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 13:2349–2359PubMedCrossRefGoogle Scholar
  209. Nijhuis M, Deeks S, Boucher C (2001) Implications of antiretroviral resistance on viral fitness. Curr Opin Infect Dis 14:23–28PubMedGoogle Scholar
  210. Novella IS, Duarte EA, Elena SF, Moya A, Domingo E, Holland JJ (1995a) Exponential increases of RNA virus fitness during large population transmissions. Proc Natl Acad Sci U S A 92:5841–5844PubMedGoogle Scholar
  211. Novella IS, Duarte EA, Elena SF, Moya A, Domingo E, Holland JJ (1995b) Exponential increases of RNA virus fitness during large population transmissions. Proc Natl Acad Sci U S A 92:5841–5844PubMedGoogle Scholar
  212. Novella IS, Ebendick-Corp (2004) Molecular basis of fitness loss and fitness recovery in vesicular stomatitis virus. J Mol Biol 342:1423–1430PubMedGoogle Scholar
  213. Novella IS, Elena SF, Moya A, Domingo E, Holland JJ (1995c) Size of genetic bottlenecks leading to virus fitness loss is determined by mean initial population fitness. J Virol 69:2869–2872PubMedGoogle Scholar
  214. Novella IS, Ball LA, Wertz GW (2004) Fitness analyses of vesicular stomatitis strains with rearranged genomes reveal replicative disadvantages. J Virol 78:9837–9841PubMedGoogle Scholar
  215. Nowak MA, Anderson RM, McLean AR, Wolfs TFW, Goudsmit J, May RM (1991) Antigenic diversity thresholds and the development of AIDS. Science 254:963–969PubMedGoogle Scholar
  216. O’Brien SJ, Moore JP (2000) The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol Rev 177:99–111PubMedGoogle Scholar
  217. O’Connor DH, Allen TM, Vogel TU, Jing P, DeSouza IP, Dodds E, Dunphy EJ, Melsaether C, Mothe B, Yamamoto H, Horton H, Wilson N, Hughes AL, Watkins DI (2002) Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nat Med 8:493–499PubMedGoogle Scholar
  218. Overbaugh J, Kreiss J, Poss M, Lewis P, Mostad S, John G, Nduati R, Mbori-Ngacha D, Martin H Jr, Richardson B, Jackson S, Neilson J, Long EM, Panteleeff D, Welch M, Rakwar J, Jackson D, Chohan B, Lavreys L, Mandaliya K, Ndinya-Achola J, Bwayo J (1999) Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya. J Infect Dis 179[Suppl 3]:S401–S404PubMedGoogle Scholar
  219. Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, Montefiori D, Orenstein JM, Fox C, Schrager LK, Margolick JB, Buchbinder S, Giorgi JV, Fauci AS (1995) Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Eng J Med 332:209–216Google Scholar
  220. Park J, Morrow CD (1993) Mutations in the protease gene of human immunodeficiency virus type 1 affect release and stability of virus particles. Virology 194:843–850PubMedCrossRefGoogle Scholar
  221. Partridge L, Barton NH (1993) Optimality, mutation and the evolution of ageing. Nature (London) 362:305–311CrossRefGoogle Scholar
  222. Peeters M (2000) Recombinant HIV sequences: their role in the global epidemic. In: Kuiken C, Foley B, Hahn B, Korber B, McCutchan F, Marx P, Mellors J, Mullins JI, Sodroski J, Wolinsky S (eds) Human retroviruses and AIDS 2000. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, pp I-39–I-54Google Scholar
  223. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271:1582–1586PubMedGoogle Scholar
  224. Petropoulos CJ, Parkin NT, Limoli KL, Lie YS, Wrin T, Huang W, Tian H, Smith D, Winslow GA, Capon DJ, Whitcomb JM (2000) A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother 44:920–928PubMedCrossRefGoogle Scholar
  225. Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, Ogunlesi AO, Elvin JG, Rothbard JA, Bangham CR, Rizza CR (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature (London) 354:453–459CrossRefGoogle Scholar
  226. Picchio GR, Valdez H, Sabbe R, Landay AL, Kuritzkes DR, Lederman MM, Mosier DE (2000) Altered viral fitness of HIV-1 following failure of protease inhibitor-based therapy. J Acquir Immune Defic Syndr 25:289–295PubMedGoogle Scholar
  227. Piyasirisilp S, McCutchan FE, Carr JK, Sanders-Buell E, Liu W, Chen J, Wagner R, Wolf H, Shao Y, Lai S, Beyrer C, Yu XF (2000) A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant. J Virol 74:11286–11295PubMedCrossRefGoogle Scholar
  228. Pontesilli O, Klein MR, Kerkhof-Garde SR, Pakker NG, de Wolf F, Schuitemaker H, Miedema F (1998) Longitudinal analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte responses: a predominant gag-specific response is associated with nonprogressive infection. J Infect Dis 178:1008–1018PubMedGoogle Scholar
  229. Prado JG, Wrin T, Beauchaine J, Ruiz L, Petropoulos CJ, Frost SD, Clotet B, D’aquila RT, Martinez-Picado J (2002) Amprenavir-resistant HIV-1 exhibits lopinavir crossresistance and reduced replication capacity. AIDS 16:1009–1017PubMedCrossRefGoogle Scholar
  230. Prado JG, Franco S, Matamoros T, Ruiz L, Clotet B, Menendez-Arias L, Martinez MA, Martinez-Picado J (2004) Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. Virology 326:103–112PubMedCrossRefGoogle Scholar
  231. Precious HM, Gunthard HF, Wong JK, D’aquila RT, Johnson VA, Kuritzkes DR, Richman DD, Leigh Brown AJ (2000) Multiple sites in HIV-1 reverse transcriptase associated with virological response to combination therapy. AIDS 14:31–36PubMedCrossRefGoogle Scholar
  232. Preston BD, Poiesz BJ, Loeb LA (1988) Fidelity of HIV-1 reverse transcriptase. Science 242:1168–1171PubMedGoogle Scholar
  233. Quinn TC (1996) Global burden of the HIV pandemic. Lancet 348:99–106PubMedGoogle Scholar
  234. Quiñones-Mateu ME, Arts EJ (1999)Recombination in HIV-1: update and implications. AIDS Reviews 1:89–100Google Scholar
  235. Quiñones-Mateu ME, Arts EJ (2001) HIV-1 fitness: implications for drug resistance, disease progression, and global epidemic evolution. In: Kuiken C, Foley B, Hahn B, Marx P, McCutchan F, Mellors J, Wolinsky S, Korber B (eds) HIV Sequence Compendium 2001. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, pp 134–170Google Scholar
  236. Quiñones-Mateu ME, Arts EJ (2002) Fitness of drug resistant HIV-1: methodology and clinical implications. Drug Resist Updat 5:224–233PubMedGoogle Scholar
  237. Quiñones-Mateu ME, Ball SC, Marozsan AJ, Torre VS, Albright JL, Vanham G, van der Groen G, Colebunders RL, Arts EJ (2000) A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J Virol 74:9222–9233PubMedGoogle Scholar
  238. Quiñones-Mateu ME, Tadele M, Parera M, Mas A, Weber J, Rangel HR, Chakraborty B, Clotet B, Domingo E, Menendez-Arias L, Martinez MA (2002) Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation. J Virol 76:10546–10552PubMedGoogle Scholar
  239. Rangel HR, Weber J, Chakraborty B, Gutierrez A, Marotta ML, Mirza M, Kiser P, Martinez MA, Este JA, Quiñones-Mateu ME (2003) Role of the human immunodeficiency virus type 1 envelope gene in viral fitness. J Virol 77:9069–9073PubMedCrossRefGoogle Scholar
  240. Resch W, Parkin N, Stuelke EL, Watkins T, Swanstrom R (2001) Amultiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics. Proc Natl Acad Sci U S A 98:176–181PubMedCrossRefGoogle Scholar
  241. Rey-Cuille MA, Berthier JL, Bomsel-Demontoy MC, Chaduc Y, Montagnier L, Hovanessian AG, Chakrabarti LA (1998) Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease. J Virol 72:3872–3886PubMedGoogle Scholar
  242. Richardson BA, Mbori-Ngacha D, Lavreys L, John-Stewart GC, Nduati R, Panteleeff DD, Emery S, Kreiss JK, Overbaugh J (2003) Comparison of human immunodeficiency virus type 1 viral loads in Kenyan women, men, and infants during primary and early infection. J Virol 77:7120–7123PubMedGoogle Scholar
  243. Richman DD, Wrin T, Little SJ, Petropoulos CJ (2003) Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 100:4144–4149PubMedCrossRefGoogle Scholar
  244. Robinson LH, Myers RE, Snowden BW, Tisdale M, Blair ED (2000) HIV type 1 protease cleavage site mutations and viral fitness: implications for drug susceptibility phenotyping assays. AIDS Res Hum Retroviruses 16:1149–1156PubMedCrossRefGoogle Scholar
  245. Rodenburg CM, Li Y, Trask SA, Chen Y, Decker J, Robertson DL, Kalish ML, Shaw GM, Allen S, Hahn BH, Gao F (2001) Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents. AIDS Res Hum Retroviruses 17:161–168PubMedCrossRefGoogle Scholar
  246. Root MJ, Kay MS, Kim PS (2001) Protein design of an HIV-1 entry inhibitor. Science 291:884–888PubMedCrossRefGoogle Scholar
  247. Rose RE, Gong YF, Greytok JA, Bechtold CM, Terry BJ, Robinson BS, Alam M, Colonno RJ, Lin PF (1996) Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors. Proc Natl Acad Sci U S A 93:1648–1653PubMedGoogle Scholar
  248. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD (1997) Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia [see comments]. Science 278:1447–1450PubMedCrossRefGoogle Scholar
  249. Rouzine IM, Coffin JM (1999) Linkage disequilibrium test implies a large effective population number for HIV in vivo. Proc Natl Acad Sci U S A 96:10758–10763PubMedCrossRefGoogle Scholar
  250. Ruiz-Jarabo CM, Miller E, Gomez-Mariano G, Domingo E (2003) Synchronous loss of quasispecies memory in parallel viral lineages: a deterministic feature of viral quasispecies. J Mol Biol 333:553–563PubMedCrossRefGoogle Scholar
  251. Sanjuan R, Moya A, Elena SF (2004) The contribution of epistasis to the architecture of fitness in an RNA virus. Proc Natl Acad Sci U S A 101:15376–15379PubMedGoogle Scholar
  252. Santiago ML, Santiago EG, Hafalla JC, Manalo MA, Orantia L, Cajimat MN, Martin C, Cuaresma C, Dominguez CE, Borromeo ME, De Groot AS, Flanigan TP, Carpenter CC, Mayer KH, Ramirez BL (1998) Molecular epidemiology of HIV-1 infection in the Philippines, 1985 to 1997: transmission of subtypes B and E and potential emergence of subtypes C and F. J Acquir Immune Defic Syndr Hum Retrovirol 18:260–269PubMedGoogle Scholar
  253. Santra S, Schmitz JE, Kuroda MJ, Lifton MA, Nickerson CE, Lord CI, Pal R, Franchini G, Letvin NL (2002) Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. J Immunol 68:1847–1853Google Scholar
  254. Schuitemaker H, Koot M, Kootstra NA, Dercksen MW, de Goede RE, van Steenwijk RP, Lange JM, Schattenkerk JK, Miedema F, Tersmette M (1992) Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol 66:1354–1360PubMedGoogle Scholar
  255. Seo TK, Thorne JL, Hasegawa M, Kishino H (2002) Estimation of effective population size of HIV-1 within a host: a pseudomaximum-likelihood approach. Genetics 160:1283–1293PubMedGoogle Scholar
  256. Shafer RW, Dupnik K, Winters MA, Eshleman SH (2000) A guide to HIV-1 reverse transcriptase and protease sequencing for drug resistance studies. HIV Sequence Compendium 2000.Google Scholar
  257. Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, Farzadegan H, Gupta P, Rinaldo CR, Learn GH, He X, Huang XL, Mullins JI (1999) Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol 73:10489–10502PubMedGoogle Scholar
  258. Sharma PL, Crumpacker CS (1997) Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation [published erratum appears in J Virol 1998; 72:3504]. J Virol 71:8846–8851PubMedGoogle Scholar
  259. Sharma PL, Crumpacker CS (1999) Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selectedmutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. J Virol 73:8448–8456PubMedGoogle Scholar
  260. Shi C, Mellors JW (1997) A recombinant retroviral system for rapid in vivo analysis of human immunodeficiency virus type 1 susceptibility to reverse transcriptase inhibitors. Antimicrob Agents Chemother 41:2781–2785PubMedGoogle Scholar
  261. Shirasaka T, Kavlick MF, Ueno T, Gao WY, Kojima E, Alcaide ML, Chokekijchai S, Roy BM, Arnold E, Yarchoan R (1995) Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci USA 92:2398–2402PubMedGoogle Scholar
  262. Shriner D, Shankarappa R, Jensen MA, Nickle DC, Mittler JE, Margolick JB, Mullins JI (2004) Influence of random genetic drift on human immunodeficiency virus type 1 env evolution during chronic infection. Genetics 166:1155–1164PubMedCrossRefGoogle Scholar
  263. Siller S (2001) Sexual selection and the maintenance of sex. Nature (London) 411:689–692CrossRefGoogle Scholar
  264. Simmonds P (2004) Genetic diversity and evolution of hepatitis C virus—15 years on. J Gen Virol 85:3173–3188PubMedCrossRefGoogle Scholar
  265. Simmons G, Clapham PR, Picard L, Offord RE, Rosenkilde MM, Schwartz TW, Buser R, Wells TN, Proudfoot AE (1997) Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 276:276–279PubMedCrossRefGoogle Scholar
  266. Simon V, Padte N, Murray D, Vanderhoeven J, Wrin T, Parkin N, Di Mascio M, Markowitz M (2003) Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection. J Virol 77:7736–7745PubMedCrossRefGoogle Scholar
  267. Sole RV, Ferrer R, Gonzalez-Garcia I, Quer J, Domingo E (1999) Red queen dynamics, competition and critical points in a model of RNA virus quasispecies. J Theor Biol 198:47–59PubMedCrossRefGoogle Scholar
  268. Soto-Ramirez LE, Renjifo B, McLane MF, Marlink R, O’Hara C, Sutthent R, Wasi C, Vithayasai P, Vithayasai V, Apichartpiyakul C, Auewarakul P, Pena Cruz V, Chui DS, Osathanondh R, Mayer K, Lee TH, Essex M (1996) HIV-1 Langerhans’ cell tropism associated with heterosexual transmission of HIV. Science 271:1291–1293PubMedGoogle Scholar
  269. Stapleton JT (2003) GB virus type C/hepatitis G virus. Semin Liver Dis 23:137–148PubMedGoogle Scholar
  270. Svarovskaia ES, Barr R, Zhang X, Pais GC, Marchand C, Pommier Y, Burke TR Jr, Pathak VK (2004) Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. J Virol 78:3210–3222PubMedCrossRefGoogle Scholar
  271. Tamiya S, Mardy S, Kavlick MF, Yoshimura K, Mistuya H (2004) Amino acid insertions near Gag cleavage sites restore the otherwise compromised replication of human immunodeficiency virus type 1 variants resistant to protease inhibitors. J Virol 78:12030–12040PubMedCrossRefGoogle Scholar
  272. Tang JW, Pillay D (2004) Transmission of HIV-1 drug resistance. J Clin Virol 30:1–10PubMedCrossRefGoogle Scholar
  273. Temin HM (1989) Is HIV unique or merely different? J Acquir Immune Defic Syndr 2:1–9PubMedGoogle Scholar
  274. Tersmette M, de Goede RE, Al BJ, Winkel IN, Gruters RA, Cuypers HT, Huisman HG, Miedema F (1988) Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol 62:2026–2032PubMedGoogle Scholar
  275. Tersmette M, Miedema F (1990) Interactions between HIV and the host immune system in the pathogenesis of AIDS. AIDS 4:S57–S66PubMedGoogle Scholar
  276. Troyer R, Collins KR, Abraha A, Fraundorf E, Moore D, Krizan RW, Toossi Z, Colebunders RL, Jensen MA, Mullins JI, Vanham G, Arts EJ (2005) Impact of ex vivo HIV-1 fitness and genetic diversity on disease progression. J Virol 79 (in press)Google Scholar
  277. Turner PE, Chao L (1999) Prisoner’s dilemma in an RNA virus. Nature (London) 398:441–443CrossRefGoogle Scholar
  278. Turner PE, Elena SF (2000) Cost of host radiation in an RNA virus. Genetics 156:1465–1470PubMedGoogle Scholar
  279. Van Harmelen JH, van der RE, Loubser AS, York D, Madurai S, Lyons S, Wood R, Williamson C (1999) A predominantly HIV type 1 subtype C-restricted epidemic in South African urban populations. AIDS Res Hum Retroviruses 15:395–398PubMedCrossRefGoogle Scholar
  280. Van Harmelen J, Williamson C, Kim B, Morris L, Carr J, Karim SS, McCutchan F (2001) Characterization of full-length HIV type 1 subtype Csequences from South Africa. AIDS Res Hum Retroviruses 17:1527–1531PubMedGoogle Scholar
  281. Velazquez-Campoy A, Todd MJ, Vega S, Freire E (2001) Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes. Proc Natl Acad Sci U S A 98:6062–6067PubMedCrossRefGoogle Scholar
  282. Weaver SC, Brault AC, Kang W, Holland JJ (1999) Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. J Virol 73:4316–4326PubMedGoogle Scholar
  283. Weber J, Rangel HR, Chakraborty B, Marotta ML, Valdez H, Fransen K, Florence E, Connick E, Smith K, Colebunders R, Landay A, Kuritzkes DR, Lederman MM, Vanham G, Quiñones-Mateu ME (2003a) Role of baseline pol genotype in HIV-1 fitness evolution. JAIDS 33:448–460PubMedGoogle Scholar
  284. Weber J, Rangel HR, Chakraborty B, Tadele M, Martinez MA, Martinez-Picado J, Marotta ML, Mirza M, Ruiz L, Clotet B, Wrin T, Petropoulos CJ, Quiñones-Mateu ME (2003b) A novel TaqMan real-time PCR assay to estimate ex vivo human immunodeficiency virus type 1 fitness in the era of multi-target (pol and env) antiretroviral therapy. J Gen Virol 84:2217–2228PubMedGoogle Scholar
  285. Weber J, Chakraborty B, Weberova J, Miller MD, Quiñones-Mateu ME (2005) Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. J Clin Microbiol 43:1395–1400PubMedCrossRefGoogle Scholar
  286. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature (London) 373:117–122CrossRefGoogle Scholar
  287. Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, Saag MS, Wu X, Shaw GM, Kappes JC (2002) Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46:1896–1905PubMedCrossRefGoogle Scholar
  288. Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM (2003) Antibody neutralization and escape by HIV-1. Nature (London) 422:307–312CrossRefGoogle Scholar
  289. Whetter LE, Ojukwu IC, Novembre FJ, Dewhurst S (1999) Pathogenesis of simian immunodeficiency virus infection. J Gen Virol 80:1557–1568PubMedGoogle Scholar
  290. White HD, Robbins MD, Green WR (1990) Mechanism of escape of endogenous murine leukemia virus emv-14 from recognition by anti-AKR/Gross virus cytolytic T lymphocytes. J Virol 64:2608–2619PubMedGoogle Scholar
  291. White KL, Margot NA, Wrin T, Petropoulos CJ, Miller MD, Naeger LK (2002) Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Antimicrob Agents Chemother 46:3437–3446PubMedGoogle Scholar
  292. Winston A, Mandalia S, Pillay D, Gazzard B, Pozniak A (2002) The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovirnaive patients. AIDS 16:2087–2089PubMedCrossRefGoogle Scholar
  293. Wodarz D, Nowak MA (1998) The effect of different immune responses on the evolution of virulent CXCR4-tropic HIV. Proc R Soc Lond B Biol Sci 265:2149–2158Google Scholar
  294. Wolinsky SM, Wike CM, Korber BT, Hutto C, Parks WP, Rosenblum LL, Kunstman KJ, Furtado MR, Munoz JL (1992) Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants [see comments]. Science 255:1134–1137PubMedGoogle Scholar
  295. Wrin T, Gamarnik A, Whitehurst N, Beauchaine J, Whitcomb JM, Hellmann NS, Petropoulos CJ (2001) Natural variation of replication capacity measurements in drug-naive/susceptible HIV-1. 5th International Workshop on HIV Drug Resistance and Treatment Strategies, Scottsdale, Arizona June 2001, Abstract 24Google Scholar
  296. Yoshimura K, Feldman R, Kodama E, Kavlick MF, Qiu YL, Zemlicka J, Mitsuya H (1999) In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. Antimicrob Agents Chemother 43:2479–2483PubMedGoogle Scholar
  297. Yuste E, Sanchez-Palomino S, Casado C, Domingo E, Lopez-Galindez C (1999) Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events. J Virol 73:2745–2751PubMedGoogle Scholar
  298. Yuste E, Lopez-Galindez C, Domingo E (2000) Unusual distribution of mutations associated with serial bottleneck passages of human immunodeficiency virus type 1. J Virol 74:9546–9552PubMedCrossRefGoogle Scholar
  299. Zennou V, Mammano F, Paulous S, Mathez D, Clavel F (1998) Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects in human immunodeficiency virus type 1 variants selected for resistance to protease inhibitors in vivo. J Virol 72:3300–3306PubMedGoogle Scholar
  300. Zhang D, Caliendo AM, Eron JJ, DeVore KM, Kaplan JC, Hirsch MS, D’aquila RT (1994) Resistance to 2′,3′-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 38:282–287PubMedGoogle Scholar
  301. Zhang H, Zhou Y, Alcock C, Kiefer T, Monie D, Siliciano J, Li Q, Pham P, Cofrancesco J, Persaud D, Siliciano RF (2004) Novel single-cell-level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant human immunodeficiency virus type 1. J Virol 78:1718–1729PubMedGoogle Scholar
  302. Zhang YM, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari MB, Salzman NP (1997) Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites. J Virol 71:6662–6670PubMedGoogle Scholar
  303. Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD (1993) Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179–1181PubMedGoogle Scholar
  304. Zhu T, Wang N, Carr A, Nam DS, Moor-Jankowski R, Cooper DA, Ho DD (1996) Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. J Virol 70:3098–3107PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • M. E. Quiñones-Mateu
    • 1
  • E. J. Arts
    • 2
  1. 1.Department of Molecular Genetics, Section Virology, Lerner Research InstituteCleveland Clinic FoundationClevelandUSA
  2. 2.Division of Infectious Diseases, Department of MedicineCase Western Reserve UniversityClevelandUSA

Personalised recommendations