Current HIV/AIDS Reports

, 4:36 | Cite as

The impact of viral and host elements on HIV fitness and disease progression

  • Kenneth R. Henry
  • Jan Weber
  • Miguel E. Quiñones-Mateu
  • Eric J. Arts
Article

Abstract

Twenty-five years after the emergence of HIV onto the global scene, multiple advancements have been made in the understanding of HIV pathology. Thanks to the development of antiretroviral therapies, growing numbers of individuals with HIV infection experience slowed or halted acceleration to AIDS. Despite this, new HIV infections and AIDS-related morbidity and mortality are still common in the highly active antiretroviral therapy era. Recently, we and others have identified viral replicative fitness as a major determinant of HIV disease progression, which could have a major impact in the clinical setting. Therefore, in this review, we will discuss host and viral factors that affect viral fitness and its relationship on HIV pathogenesis.

References and Recommended Reading

  1. 1.
    Jung A, Maier R, Vartanian JP, et al.: Multiply infected spleen cells in HIV patients. Nature 2002, 418:144.PubMedCrossRefGoogle Scholar
  2. 2.
    Mansky LM, Temin HM: Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol 1995, 69:5087–5094.PubMedGoogle Scholar
  3. 3.
    Lal RB, Chakrabarti S, Yang C: Impact of genetic diversity of HIV-1 on diagnosis, antiretroviral therapy and vaccine development. Indian J Med Res 2005, 121:287–314.PubMedGoogle Scholar
  4. 4.
    Domingo E, Holland JJ: RNA virus mutations and fitness for survival. Annu Rev Microbiol 1997, 51:151–178.PubMedCrossRefGoogle Scholar
  5. 5.
    Domingo E, Verdaguer N, Ochoa WF, et al.: Biochemical and structural studies with neutralizing antibodies raised against foot-and-mouth disease virus. Virus Res 1999, 62:169–175.PubMedCrossRefGoogle Scholar
  6. 6.
    Troyer RM, Collins KR, Abraha A, et al.: Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J Virol 2005, 79:9006–9018.PubMedCrossRefGoogle Scholar
  7. 7.
    Quinones-Mateu ME, Ball SC, Marozsan AJ, et al.: A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J Virol 2000, 74:9222–9233.PubMedCrossRefGoogle Scholar
  8. 8.
    Lukashov VV, Goudsmit J: Founder virus population related to route of virus transmission: a determinant of intrahost human immunodeficiency virus type 1 evolution? J Virol 1997, 71:2023–2030.PubMedGoogle Scholar
  9. 9.
    Nowak MA, Anderson RM, McLean AR, et al.: Antigenic diversity thresholds and the development of AIDS. Science 1991, 254:963–969.PubMedCrossRefGoogle Scholar
  10. 10.
    Nowak MA, May RM, Phillips RE, et al.: Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 1995, 375:606–611.PubMedCrossRefGoogle Scholar
  11. 11.
    Delwart EL, Pan H, Sheppard HW, et al.: Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS. J Virol 1997, 71:7498–7508.PubMedGoogle Scholar
  12. 12.
    Wu H, Kuritzkes DR, McClernon DR, et al.: Characterization of viral dynamics in human immunodeficiency virus type 1—infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points. J Infect Dis 1999, 179:799–807.PubMedCrossRefGoogle Scholar
  13. 13.
    Quinones-Mateu ME, Gao Y, Ball SC, et al.: In vitro intersubtype recombinants of human immunodeficiency virus type 1: comparison to recent and circulating in vivo recombinant forms. J Virol 2002, 76:9600–9613.PubMedCrossRefGoogle Scholar
  14. 14.
    Shankarappa R, Gupta P, Learn GH Jr, et al.: Evolution of human immunodeficiency virus type 1 envelope sequences in infected individuals with differing disease progression profiles. Virology 1998, 241:251–259.PubMedCrossRefGoogle Scholar
  15. 15.
    Shankarappa R, Margolick JB, Gange SJ, et al.: Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol 1999, 73:10489–10502.PubMedGoogle Scholar
  16. 16.
    Clarke DK, Duarte EA, Elena SF, et al.: The red queen reigns in the kingdom of RNA viruses. Proc Natl Acad Sci U S A 1994, 91:4821–4824.PubMedCrossRefGoogle Scholar
  17. 17.
    Escarmis C, Carrillo EC, Ferrer M, et al.: Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism. J Virol 1998, 72:10171–10179.PubMedGoogle Scholar
  18. 18.
    Novella IS, Duarte EA, Elena SF, et al.: Exponential increases of RNA virus fitness during large population transmissions. Proc Natl Acad Sci U S A 1995, 92:5841–5844.PubMedCrossRefGoogle Scholar
  19. 19.
    Pantaleo G, Graziosi C, Fauci AS: The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993, 328:327–335.PubMedCrossRefGoogle Scholar
  20. 20.
    Brenchley JM, Schacker TW, Ruff LE, et al.: CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004, 200:749–759.PubMedCrossRefGoogle Scholar
  21. 21.
    Guadalupe M, Reay E, Sankaran S, et al.: Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003, 77:11708–11717.PubMedCrossRefGoogle Scholar
  22. 22.
    Mehandru S, Poles MA, Tenner-Racz K, et al.: Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004, 200:761–770.PubMedCrossRefGoogle Scholar
  23. 23.
    Picker LJ, Watkins DI: HIV pathogenesis: the first cut is the deepest. Nat Immunol 2005, 6:430–432.PubMedCrossRefGoogle Scholar
  24. 24.
    Pierson TC, Doms RW: HIV-1 entry and its inhibition. Curr Top Microbiol Immunol 2003, 281:1–27.PubMedGoogle Scholar
  25. 25.
    Poveda E, Briz V, Quinones-Mateu M, et al.: HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS 2006, 20:1359–1367.PubMedCrossRefGoogle Scholar
  26. 26.
    Ho DD: HIV-1 dynamics in vivo. J Biol Regul Homeost Agents 1995, 9:76–77.PubMedGoogle Scholar
  27. 27.
    Lazaro E, Escarmis C, Perez-Mercader J, et al.: 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 2003, 100:10830–10835.PubMedCrossRefGoogle Scholar
  28. 28.
    Dean M, Carrington M, Winkler C, et al.: 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 1996, 273:1856–1862.PubMedCrossRefGoogle Scholar
  29. 29.
    Martin MP, Dean M, Smith MW, et al.: Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science 1998, 282:1907–1911.PubMedCrossRefGoogle Scholar
  30. 30.
    Fortis C, Poli G: Dendritic cells and natural killer cells in the pathogenesis of HIV infection. Immunol Res 2005, 33:1–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Goodenow MM, Rose SL, Tuttle DL, et al.: HIV-1 fitness and macrophages. J Leukoc Biol 2003, 74:657–666.PubMedCrossRefGoogle Scholar
  32. 32.
    Turville S, Wilkinson J, Cameron P, et al.: The role of dendritic cell C-type lectin receptors in HIV pathogenesis. J Leukoc Biol 2003, 74:710–718.PubMedCrossRefGoogle Scholar
  33. 33.
    Valentin A, Pavlakis GN: Natural killer cells are persistently infected and resistant to direct killing by HIV-1. Anticancer Res 2003, 23:2071–2075.PubMedGoogle Scholar
  34. 34.
    Valentin A, Rosati M, Patenaude DJ, et al.: Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy. Proc Natl Acad Sci U S A 2002, 99:7015–7020.PubMedCrossRefGoogle Scholar
  35. 35.
    Alkhatib G, Combadiere C, Broder CC, et al.: CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996, 272:1955–1958.PubMedCrossRefGoogle Scholar
  36. 36.
    Amara A, Gall SL, Schwartz O, et al.: HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J Exp Med 1997, 186:139–146.PubMedCrossRefGoogle Scholar
  37. 37.
    Aramori I, Ferguson SS, Bieniasz PD, et al.: Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor. Embo J 1997, 16:4606–4616.PubMedCrossRefGoogle Scholar
  38. 38.
    Arenzana-Seisdedos F, Virelizier JL, Rousset D, et al.: HIV blocked by chemokine antagonist. Nature 1996, 383:400.PubMedCrossRefGoogle Scholar
  39. 39.
    Bleul CC, Farzan M, Choe H, et al.: The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996, 382:829–833.PubMedCrossRefGoogle Scholar
  40. 40.
    Mack M, Schlondorff D: Downmodulation and recycling of chemokine receptors. Methods Mol Biol 2000, 138:191–195.PubMedGoogle Scholar
  41. 41.
    Gallo RC, Garzino-Demo A, DeVico AL: HIV infection and pathogenesis: what about chemokines? J Clin Immunol 1999, 19:293–299.PubMedCrossRefGoogle Scholar
  42. 42.
    Gonzalez E, Kulkarni H, Bolivar H, et al.: The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005, 307:1434–1440.PubMedCrossRefGoogle Scholar
  43. 43.
    Cilliers T, Willey S, Sullivan WM, et al.: Use of alternate coreceptors on primary cells by two HIV-1 isolates. Virology 2005, 339:136–144.PubMedCrossRefGoogle Scholar
  44. 44.
    Este JA, Cabrera C, Blanco J, et al.: Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing pheno-type by blockade of CXCR4. J Virol 1999, 73:5577–5585.PubMedGoogle Scholar
  45. 45.
    Mosier DE, Picchio GR, Gulizia RJ, et al.: Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type 1 infection in vivo or rapidly select for CXCR4-using variants. J Virol 1999, 73:3544–3550.PubMedGoogle Scholar
  46. 46.
    Schols D, Este JA, Cabrera C, et al.: T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1alpha contains mutations in the envelope gp120 but does not show a switch in coreceptor use. J Virol 1998, 72:4032–4037.PubMedGoogle Scholar
  47. 47.
    Torre VS, Marozsan AJ, Albright JL, et al.: Variable sensitivity of CCR5-tropic human immunodeficiency virus type 1 isolates to inhibition by RANTES analogs. J Virol 2000, 74:4868–4876.PubMedCrossRefGoogle Scholar
  48. 48.
    Karlsson I, Antonsson L, Shi Y, et al.: Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human immunodeficiency virus type 1 of the R5 phenotype. J Virol 2004, 78:11807–11815.PubMedCrossRefGoogle Scholar
  49. 49.
    Carrington M, Nelson GW, Martin MP, et al.: HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 1999, 283:1748–1752.PubMedCrossRefGoogle Scholar
  50. 50.
    Gao X, Nelson GW, Karacki P, et al.: Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med 2001, 344:1668–1675.PubMedCrossRefGoogle Scholar
  51. 51.
    Kaslow RA, Carrington M, Apple R, et al.: Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 1996, 2:405–411.PubMedCrossRefGoogle Scholar
  52. 52.
    Kamp W, Berk MB, Visser CJ, et al.: Mechanisms of HIV-1 to escape from the host immune surveillance. Eur J Clin Invest 2000, 30:740–746.PubMedCrossRefGoogle Scholar
  53. 53.
    Allen TM, Altfeld M, Geer SC, et al.: Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. J Virol 2005, 79:13239–13249.PubMedCrossRefGoogle Scholar
  54. 54.
    Fernandez CS, Stratov I, De Rose R, et al.: Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost. J Virol 2005, 79:5721–5731.PubMedCrossRefGoogle Scholar
  55. 55.
    Friedrich TC, Dodds EJ, Yant LJ, et al.: Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nat Med 2004, 10:275–281.PubMedCrossRefGoogle Scholar
  56. 56.
    Friedrich TC, Frye CA, Yant LJ, et al.: Extraepitopic compensatory substitutions partially restore fitness to simian immunodeficiency virus variants that escape from an immunodominant cytotoxic-T-lymphocyte response. J Virol 2004, 78:2581–2585.PubMedCrossRefGoogle Scholar
  57. 57.
    Martinez-Picado J, Prado JG, Fry EE, et al.: Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol 2006, 80:3617–3623.PubMedCrossRefGoogle Scholar
  58. 58.
    Troyer R, Abraha A, Krizan R, et al.: The fitness cost of CTL escape: not a terrible hardship on HIV-1? Paper presented at the XVI International AIDS Conference. Toronto, Canada; August 13–19, 2006.Google Scholar
  59. 59.
    Richman DD, Wrin T, Little SJ, et al.: Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 2003, 100:4144–4149.PubMedCrossRefGoogle Scholar
  60. 60.
    Arien KK, Gali Y, El-Abdellati A, et al.: Replicative fitness of CCR5-using and CXCR4-using human immunodeficiency virus type 1 biological clones. Virology 2006, 347:65–74.PubMedCrossRefGoogle Scholar
  61. 61.
    Ball SC, Abraha A, Collins KR, et al.: Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C. J Virol 2003, 77:1021–1038.PubMedCrossRefGoogle Scholar
  62. 62.
    Marozsan AJ, Moore DM, Lobritz MA, et al.: Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry. J Virol 2005, 79:7121–7134.PubMedCrossRefGoogle Scholar
  63. 63.
    Rangel HR, Weber J, Chakraborty B, et al.: Role of the human immunodeficiency virus type 1 envelope gene in viral fitness. J Virol 2003, 77:9069–9073.PubMedCrossRefGoogle Scholar
  64. 64.
    Deacon NJ, Tsykin A, Solomon A, et al.: Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995, 270:988–991.PubMedCrossRefGoogle Scholar
  65. 65.
    Kirchhoff F, Greenough TC, Brettler DB, et al.: Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 1995, 332:228–232.PubMedCrossRefGoogle Scholar
  66. 66.
    Daniel MD, Kirchhoff F, Czajak SC, et al.: Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 1992, 258:1938–1941.PubMedCrossRefGoogle Scholar
  67. 67.
    Schindler M, Munch J, Kutsch O, et al.: Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 2006, 125:1055–1067.PubMedCrossRefGoogle Scholar
  68. 68.
    Quinones-Mateu ME, Arts EJ: Recombination in human immunodeficiency virus type-1 (HIV-1): update and implications. AIDS Review 1999, 1:89–100.Google Scholar
  69. 69.
    Konings FA, Burda ST, Urbanski MM, et al.: Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 02_AG (CRF02_AG) has a higher in vitro replicative capacity than its parental subtypes A and G. J Med Virol 2006, 78:523–534.PubMedCrossRefGoogle Scholar
  70. 70.
    Quinones-Mateu ME, Arts EJ: Virus fitness: concept, quantification, and application to HIV population dynamics. Curr Top Microbiol Immunol 2006, 299:83–140.PubMedCrossRefGoogle Scholar
  71. 71.
    Kimata JT, Kuller L, Anderson DB, et al.: Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med 1999, 5:535–541.PubMedCrossRefGoogle Scholar
  72. 72.
    Whetter LE, Ojukwu IC, Novembre FJ, et al.: Pathogenesis of simian immunodeficiency virus infection. J Gen Virol 1999, 80:1557–1568.PubMedGoogle Scholar
  73. 73.
    Holterman L, Niphuis H, Koornstra W, et al.: The rate of progression to AIDS is independent of virus dose in simian immunodeficiency virus-infected macaques. J Gen Virol 2000, 81:1719–1726.PubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  • Kenneth R. Henry
  • Jan Weber
  • Miguel E. Quiñones-Mateu
  • Eric J. Arts
    • 1
  1. 1.Division of Infectious Diseases, BRB 1029Case Western Reserve UniversityClevelandUSA

Personalised recommendations