Current HIV/AIDS Reports

, Volume 9, Issue 1, pp 52–63 | Cite as

The HIV-1 Env Protein: A Coat of Many Colors

  • Kathryn Twigg Arrildt
  • Sarah Beth Joseph
  • Ronald Swanstrom
The Science of HIV (AL Landay, Section Editor)

Abstract

HIV-1 is completely dependent upon the Env protein to enter cells. The virus typically replicates in activated CD4+ T cells due to viral entry requirements for the CCR5 coreceptor and for high surface levels of the CD4 receptor. This is the case for the transmitted virus and for most of the virus sampled in the blood. Over the course of infection, the env gene can evolve to encode a protein with altered receptor and coreceptor usage allowing the virus to enter alternative host cells. In about 50% of HIV-1 infections, the viral population undergoes coreceptor switching, usually late in disease, allowing the virus to use CXCR4 to enter a different subset of CD4+ T cells. Neurocognitive disorders occur in about 10% of infections, also usually late in disease, but caused (ultimately) by viral replication in the brain either in CD4+ T cells or macrophage and/or microglia. Expanded host range is significantly intertwined with pathogenesis. Identification and characterization of such HIV-1 variants may be useful for early detection which would allow intervention to reduce viral pathogenesis in these alternative cell types.

Keywords

Human immunodeficiency virus HIV Envelope Env gp160 gp120 gp41 Tropism Macrophage Monocyte Receptor CD4 Coreceptor CCR5 R5 CXCR4 X4 Transmission Evolution Entry 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Leitner T, Kumar S, Albert J. Tempo and mode of nucleotide substitutions in gag and env gene fragments in human immunodeficiency virus type 1 populations with a known transmission history. J Virol. 1997;71:4761–70.PubMedGoogle Scholar
  2. 2.
    Asjo B, Morfeldt-Manson L, Albert J, et al. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986;2:660–2.PubMedGoogle Scholar
  3. 3.
    Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol. 1999;17:657–700.PubMedCrossRefGoogle Scholar
  4. 4.
    Douek DC, Brenchley JM, Betts MR, et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature. 2002;417:95–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Brenchley JM, Hill BJ, Ambrozak DR, et al. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol. 2004;78:1160–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Sleasman JW, Aleixo LF, Morton A, et al. CD4+ memory T cells are the predominant population of HIV-1-infected lymphocytes in neonates and children. AIDS. 1996;10:1477–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Alexander M, Lynch R, Mulenga J, et al. Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry. J Virol. 2010;84:4100–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Isaacman-Beck J, Hermann EA, Yi Y, et al. Heterosexual transmission of human immunodeficiency virus type 1 subtype C: macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization. J Virol. 2009;83:8208–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Gartner S, Markovits P, Markovitz DM, et al. The role of mononuclear phagocytes in HTLV-III LAV infection. Science. 1986;233:215–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Brown RJP, Peters PJ, Caron C, et al. Intercompartmental recombination of HIV-1 contributes to env intrahost diversity and modulates viral tropism and sensitivity to entry inhibitors. J Virol. 2011;85:6024–37.PubMedCrossRefGoogle Scholar
  11. 11.
    Peters PJ, Sullivan WM, Duenas-Decamp MJ, et al. Non-macrophage-tropic human immunodeficiency virus type 1 R5 envelopes predominate in blood, lymph nodes, and semen: implications for transmission and pathogenesis. J Virol. 2006;80:6324–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Thomas ER, Dunfee RL, Stanton J, et al. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion. Virology. 2007;360:105–19.PubMedCrossRefGoogle Scholar
  13. 13.
    • Schnell G, Joseph S, Spudich SS, et al. Two classes of viral encephalitis contribute to the development of HIV-1-associated dementia. PLoS Pathog In press. This paper demonstrates the production of macrophage-tropic virus from a long-lived cell in a subset of subjects with HIV-associated dementia.Google Scholar
  14. 14.
    • Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 2008;105:7552-7. This paper demonstrates that in most transmissions of HIV-1, the systemic infection is derived from a single viral genome. PubMedCrossRefGoogle Scholar
  15. 15.
    Abrahams MR, Anderson JA, Giorgi EE, et al. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol. 2009;83:3556–67.PubMedCrossRefGoogle Scholar
  16. 16.
    Fischer W, Ganusov VV, Giorgi EE, et al. Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PLoS One. 2010;5:e12303.PubMedCrossRefGoogle Scholar
  17. 17.
    Li H, Bar KJ, Wang S, et al. High multiplicity infection by HIV-1 in men who have sex with men. PLoS Pathog. 2010;6:e1000890.PubMedCrossRefGoogle Scholar
  18. 18.
    Gottlieb GS, Nickle DC, Jensen MA, et al. Dual HIV-1 infection associated with rapid disease progression. Lancet. 2004;363:619–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Anderson JA, Ping LH, Dibben O, et al. HIV-1 populations in semen arise through multiple mechanisms. PLoS Pathog. 2010;6:e1001053.PubMedCrossRefGoogle Scholar
  20. 20.
    Chohan B, Lang D, Sagar M, et al. Selection for human immunodeficiency virus type 1 envelope glycosylation variants with shorter V1-V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels. J Virol. 2005;79:6528–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Derdeyn CA, Decker JM, Bibollet-Ruche F, et al. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science. 2004;303:2019–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Russell ES, Kwiek JJ, Keys J, et al. The genetic bottleneck in vertical transmission of subtype C HIV-1 Is not driven by selection of especially neutralization resistant virus from the maternal viral population. J Virol 2011;8253-62.Google Scholar
  23. 23.
    Nawaz F, Cicala C, Van Ryk D, et al. The genotype of early-transmitting HIV gp120s promotes alphabeta-reactivity, revealing alphabetaCD4+ T cells as key targets in mucosal transmission. PLoS Pathog. 2011;7:e1001301.PubMedCrossRefGoogle Scholar
  24. 24.
    Richman DD, Wrin T, Little SJ, Petropoulos CJ. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A. 2003;100:4144–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Moore PL, Gray ES, Morris L. Specificity of the autologous neutralizing antibody response. Curr Opin HIV AIDS. 2009;4:358–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Ince WL, Zhang L, Jiang Q, et al. Evolution of the HIV-1 env gene in the Rag2-/- gammaC-/- humanized mouse model. J Virol. 2010;84:2740–52.PubMedCrossRefGoogle Scholar
  27. 27.
    Pugach P, Kuhmann SE, Taylor J, et al. The prolonged culture of human immunodeficiency virus type 1 in primary lymphocytes increases its sensitivity to neutralization by soluble CD4. Virology. 2004;321:8–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Shibata J, Yoshimura K, Honda A, et al. Impact of V2 mutations on escape from a potent neutralizing anti-V3 monoclonal antibody during in vitro selection of a primary human immunodeficiency virus type 1 isolate. J Virol. 2007;81:3757–68.PubMedCrossRefGoogle Scholar
  29. 29.
    Binley JM, Ban YE, Crooks ET, et al. Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization. J Virol. 2010;84:5637–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Wei X, Decker JM, Wang S, et al. Antibody neutralization and escape by HIV-1. Nature. 2003;422:307–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Bosch ML, Andeweg AC, Schipper R, Kenter M. Insertion of N-linked glycosylation sites in the variable regions of the human immunodeficiency virus type 1 surface glycoprotein through AAT triplet reiteration. J Virol. 1994;68:7566–9.PubMedGoogle Scholar
  32. 32.
    Kitrinos KM, Hoffman NG, Nelson JA, Swanstrom R. Turnover of env variable region 1 and 2 genotypes in subjects with late-stage human immunodeficiency virus type 1 infection. J Virol. 2003;77:6811–22.PubMedCrossRefGoogle Scholar
  33. 33.
    Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993;118:681–8.PubMedGoogle Scholar
  34. 34.
    Connor RI, Sheridan KE, Ceradini D, et al. Change in coreceptor use correlates with disease progression in HIV-1–infected individuals. J Exp Med. 1997;185:621–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hunt PW, Harrigan PR, Huang W, et al. Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia. J Infect Dis. 2006;194:926–30.PubMedCrossRefGoogle Scholar
  36. 36.
    Bleul CC, Wu L, Hoxie JA, et al. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A. 1997;94:1925–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Lee B, Sharron M, Montaner LJ, et al. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A. 1999;96:5215–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Blaak H, van’t Wout AB, Brouwer M, et al. In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline. Proc Natl Acad Sci U S A. 2000;97:1269–74.PubMedCrossRefGoogle Scholar
  39. 39.
    Heeregrave EJ, Geels MJ, Brenchley JM, et al. Lack of in vivo compartmentalization among HIV-1 infected naive and memory CD4+ T cell subsets. Virology. 2009;393:24–32.PubMedCrossRefGoogle Scholar
  40. 40.
    van Rij RP, Blaak H, Visser JA, et al. Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1. J Clin Invest. 2000;106:1569.PubMedCrossRefGoogle Scholar
  41. 41.
    Ince WL, Harrington PR, Schnell GL, et al. Major coexisting human immunodeficiency virus type 1 env gene subpopulations in the peripheral blood are produced by cells with similar turnover rates and show little evidence of genetic compartmentalization. J Virol. 2009;83:4068–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Hwang SS, Boyle TJ, Lyerly HK, Cullen BR. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991;253:71–4.PubMedCrossRefGoogle Scholar
  43. 43.
    de Jong JJ, Goudsmit J, Keulen W, et al. Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol. 1992;66:757–65.PubMedGoogle Scholar
  44. 44.
    Milich L, Margolin BH, Swanstrom R. Patterns of amino acid variability in NSI-like and SI-like V3 sequences and a linked change in the CD4-binding domain of the HIV-1 Env protein. Virology. 1997;239:108–18.PubMedCrossRefGoogle Scholar
  45. 45.
    Jensen MA, Li FS, van ’t Wout AB, et al. Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol. 2003;77:13376–88.PubMedCrossRefGoogle Scholar
  46. 46.
    Resch W, Hoffman N, Swanstrom R. Improved success of phenotype prediction of the human immunodeficiency virus type 1 from envelope variable loop 3 sequence using neural networks. Virology. 2001;288:51–62.PubMedCrossRefGoogle Scholar
  47. 47.
    Hoffman NG, Seillier-Moiseiwitsch F, Ahn J, et al. Variability in the human immunodeficiency virus type 1 gp120 Env protein linked to phenotype-associated changes in the V3 loop. J Virol. 2002;76:3852–64.PubMedCrossRefGoogle Scholar
  48. 48.
    Huang W, Toma J, Fransen S, et al. Coreceptor tropism can be influenced by amino acid substitutions in the gp41 transmembrane subunit of human immunodeficiency virus type 1 envelope protein. J Virol. 2008;82:5584–93.PubMedCrossRefGoogle Scholar
  49. 49.
    Tscherning C, Alaeus A, Fredriksson R, et al. Differences in chemokine coreceptor usage between genetic subtypes of HIV-1. Virology. 1998;241:181–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Huang W, Eshleman SH, Toma J, et al. Coreceptor tropism in human immunodeficiency virus type 1 subtype D: high prevalence of CXCR4 tropism and heterogeneous composition of viral populations. J Virol. 2007;81:7885–93.PubMedCrossRefGoogle Scholar
  51. 51.
    Sina ST, Ren W, Cheng-Mayer C. Coreceptor use in nonhuman primate models of HIV infection. J Transl Med. 2011;9 Suppl 1:S7.PubMedCrossRefGoogle Scholar
  52. 52.
    Ho SH, Tasca S, Shek L, et al. Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques. J Virol. 2007;81:8621–33.PubMedCrossRefGoogle Scholar
  53. 53.
    Nishimura Y, Shingai M, Willey R, et al. Generation of the pathogenic R5-tropic simian/human immunodeficiency virus SHIVAD8 by serial passaging in rhesus macaques. J Virol. 2010;84:4769–81.PubMedCrossRefGoogle Scholar
  54. 54.
    Ren W, Tasca S, Zhuang K, et al. Different tempo and anatomic location of dual-tropic and X4 virus emergence in a model of R5 simian-human immunodeficiency virus infection. J Virol. 2010;84:340–51.PubMedCrossRefGoogle Scholar
  55. 55.
    Ho SH, Shek L, Gettie A, et al. V3 loop-determined coreceptor preference dictates the dynamics of CD4 + -T-cell loss in simian-human immunodeficiency virus-infected macaques. J Virol. 2005;79:12296–303.PubMedCrossRefGoogle Scholar
  56. 56.
    Nishimura Y, Igarashi T, Donau OK, et al. Highly pathogenic SHIVs and SIVs target different CD4+ T cell subsets in rhesus monkeys, explaining their divergent clinical courses. Proc Natl Acad Sci U S A. 2004;101:12324–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Dunfee RL, Thomas ER, Gorry PR, et al. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A. 2006;103:15160–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Dunfee RL, Thomas ER, Wang J, et al. Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia. Virology. 2007;367:222–34.PubMedCrossRefGoogle Scholar
  59. 59.
    Harrington PR, Haas DW, Ritola K, Swanstrom R. Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal fluid is produced by short-lived cells. J Virol. 2005;79:7959–66.PubMedCrossRefGoogle Scholar
  60. 60.
    Harrington PR, Schnell G, Letendre SL, et al. Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS. 2009;23:907–15.PubMedCrossRefGoogle Scholar
  61. 61.
    Pillai SK, Pond SLK, Liu Y, et al. Genetic attributes of cerebrospinal fluid-derived HIV-1 env. Brain. 2006;129:1872–83.PubMedCrossRefGoogle Scholar
  62. 62.
    Ritola K, Robertson K, Fiscus SA, et al. Increased human immunodeficiency virus type 1 (HIV-1) env compartmentalization in the presence of HIV-1-associated dementia. J Virol. 2005;79:10830–4.PubMedCrossRefGoogle Scholar
  63. 63.
    • Xu Y, Zhu H, Wilcox CK, et al. Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus. J Infect Dis 2008;197:309–18. This is a provocative report identifying virus in monocytes that have lost the ability to replicate in T cells. PubMedCrossRefGoogle Scholar
  64. 64.
    Li S, Juarez J, Alali M, et al. Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates. J Virol. 1999;73:9741–55.PubMedGoogle Scholar
  65. 65.
    Sterjovski J, Roche M, Churchill MJ, et al. An altered and more efficient mechanism of CCR5 engagement contributes to macrophage tropism of CCR5-using HIV-1 envelopes. Virology. 2010;404:269–78.PubMedCrossRefGoogle Scholar
  66. 66.
    Taylor BM, Foulke JS, Flinko R, et al. An alteration of human immunodeficiency virus gp41 leads to reduced CCR5 dependence and CD4 independence. J Virol. 2008;82:5460–71.PubMedCrossRefGoogle Scholar
  67. 67.
    Peters PJ, Duenas-Decamp MJ, Sullivan WM, et al. Variation in HIV-I R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors. Retrovirology. 2008;5:5.PubMedGoogle Scholar
  68. 68.
    Roche M, Jakobsen MR, Sterjovski J, et al. HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism. J Virol. 2011;85:4330–42.PubMedCrossRefGoogle Scholar
  69. 69.
    Sterjovski J, Churchill MJ, Ellett A, et al. Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS. Retrovirology. 2007;4:89.PubMedCrossRefGoogle Scholar
  70. 70.
    Duenas-Decamp MJ, Peters P, Burton D, Clapham PR. Natural resistance of human immunodeficiency virus type 1 to the CD4bs antibody b12 conferred by a glycan and an arginine residue close to the CD4 binding loop. J Virol. 2008;82:5807–14.PubMedCrossRefGoogle Scholar
  71. 71.
    Dunfee RL, Thomas ER, Gabuzda D. Enhanced macrophage tropism of HIV in brain and lymphoid tissues is associated with sensitivity to the broadly neutralizing CD4 binding site antibody b12. Retrovirology. 2009;6:69.PubMedCrossRefGoogle Scholar
  72. 72.
    Duenas-Decamp MJ, Peters PJ, Burton D, Clapham PR. Determinants flanking the CD4 binding loop modulate macrophage tropism of human immunodeficiency virus type 1 R5 envelopes. J Virol. 2009;83:2575–83.PubMedCrossRefGoogle Scholar
  73. 73.
    • Zhuang K, Finzi A, Tasca S, et al. Adoption of an “Open” envelope conformation facilitating CD4 binding and structural remodeling precedes coreceptor switch in R5 SHIV-infected macaques. Plos One 2011;6:e21350. This paper reports a new cell line where CD4 and CCR5 are under control of regulatable promoters, allowing quantitative assessment of the need for these receptors in entry.PubMedCrossRefGoogle Scholar
  74. 74.
    Johnston SH, Lobritz MA, Nguyen S, et al. A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains. J Virol. 2009;83:11016–26.PubMedCrossRefGoogle Scholar
  75. 75.
    Duenas-Decamp MJ, Clapham PR. HIV-1 gp120 determinants proximal to the CD4 binding site shift protective glycans that are targeted by monoclonal antibody 2G12. J Virol. 2010;84:9608–12.PubMedCrossRefGoogle Scholar
  76. 76.
    Richards KH, Aasa-Chapman MMI, McKnight A, Clapham PR. Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. Retrovirology. 2010;7:48.PubMedCrossRefGoogle Scholar
  77. 77.
    Musich T, Peters PJ, Duenas-Decamp MJ, et al. A conserved determinant in the V1 Loop of HIV-1 modulates the V3 loop to prime low CD4 use and macrophage infection. J Virol. 2011;85:2397–405.PubMedCrossRefGoogle Scholar
  78. 78.
    Walter BL, Wehrly K, Swanstrom R, et al. Role of low CD4 levels in the influence of human immunodeficiency virus type 1 envelope V2 and V2 regions on entry and spread in macrophages. J Virol. 2005;79:4828–37.PubMedCrossRefGoogle Scholar
  79. 79.
    Cashin K, Roche M, Sterjovski J, et al. Alternative coreceptor requirements for efficient CCR5- and CXCR4-mediated HIV-1 entry into macrophages. J Virol In press.Google Scholar
  80. 80.
    Ghaffari G, Tuttle DL, Briggs D, et al. Complex determinants in human immunodeficiency virus type 1 envelope gp120 mediate CXCR4-dependent infection of macrophages. J Virol. 2005;79:13250–61.PubMedCrossRefGoogle Scholar
  81. 81.
    Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669–92.PubMedCrossRefGoogle Scholar
  82. 82.
    Grage-Griebenow E, Flad HD, Ernst M. Heterogeneity of human peripheral blood monocyte subsets. J Leuk Biol. 2001;69:11–20.Google Scholar
  83. 83.
    Ellery PJ, Tippett E, Chiu YL, et al. The CD16(+) monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol. 2007;178:6581–9.PubMedGoogle Scholar
  84. 84.
    Wong KL, Tai JJ, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118:e16–31.PubMedCrossRefGoogle Scholar
  85. 85.
    Crowe S, Zhu TF, Muller WA. The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. J Leuk Biol. 2003;74:635–41.CrossRefGoogle Scholar
  86. 86.
    Fogg DK, Sibon C, Miled C, et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science. 2006;311:83–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116:E74–80.PubMedCrossRefGoogle Scholar
  88. 88.
    Naif HM, Li S, Alali M, et al. CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection. J Virol. 1998;72:830–6.PubMedGoogle Scholar
  89. 89.
    Sonza S, Maerz A, Uren S, et al. Susceptibility of human monocytes to HIV type 1 infection in vitro is not dependent on their level of CD4 expression. AIDS Res Hum Retroviruses. 1995;11:769–76.PubMedCrossRefGoogle Scholar
  90. 90.
    Dong C, Kwas C, Wu L. Transcriptional restriction of human immunodeficiency virus type 1 gene expression in undifferentiated primary monocytes. J Virol. 2009;83:3518–27.PubMedCrossRefGoogle Scholar
  91. 91.
    Sung T-L, Rice AP. miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1. Plos Pathog. 2009;5:e1000263.PubMedCrossRefGoogle Scholar
  92. 92.
    Lewin SR, Lambert P, Deacon NJ, et al. Constitutive expression of p50 homodimer in freshly isolated human monocytes decreases in vitro and in vivo differentiation: a possible mechanism influencing human immunodeficiency virus replication in monocytes and mature macrophages. J Virol. 1997;71:2114–9.PubMedGoogle Scholar
  93. 93.
    Arfi V, Riviere L, Jarrosson-Wuilleme L, et al. Characterization of the early steps of infection of primary blood monocytes by human immunodeficiency virus type 1. J Virol. 2008;82:6557–65.PubMedCrossRefGoogle Scholar
  94. 94.
    Meuret G, Bammert J, Hoffmann G. Kinetics of human monocytopoiesis. Blood. 1974;44:801–16.PubMedGoogle Scholar
  95. 95.
    Zhu TF, Muthui D, Holte S, et al. Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol. 2002;76:707–16.PubMedCrossRefGoogle Scholar
  96. 96.
    Sonza S, Mutimer HP, Oelrichs R, et al. Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AIDS. 2001;15:17–22.PubMedCrossRefGoogle Scholar
  97. 97.
    Riddick NE, Hermann EA, Loftin LM, et al. A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo. PLoS Pathog. 2010;6:e1001064.PubMedCrossRefGoogle Scholar
  98. 98.
    Dumonceaux J, Nisole S, Chanel C, et al. Spontaneous mutations in the env gene of the human immunodeficiency virus type 1 NDK isolate are associated with a CD4-independent entry phenotype. J Virol. 1998;72:512–9.PubMedGoogle Scholar
  99. 99.
    Haim H, Strack B, Kassa A, et al. Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity. Plos Pathog. 2011;7:e1002101.PubMedCrossRefGoogle Scholar
  100. 100.
    Hoffman TL, LaBranche CC, Zhang WT, et al. Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc Natl Acad Sci U S A. 1999;96:6359–64.PubMedCrossRefGoogle Scholar
  101. 101.
    Kolchinsky P, Mirzabekov T, Farzan M, et al. Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication. J Virol. 1999;73:8120–6.PubMedGoogle Scholar
  102. 102.
    Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nature Medicine. 2002;8:522–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Edwards TG, Hoffman TL, Baribaud F, et al. Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein. J Virol. 2001;75:5230–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Eitner F, Cui Y, Hudkins KL, et al. Chemokine receptor CCR5 and CXCR4 expression in HIV-associated kidney disease. J Am Soc Nephrol. 2000;11:856–67.PubMedGoogle Scholar
  105. 105.
    Bruggeman LA, Ross MD, Tanji N, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. J Am Soc Nephrol. 2000;11:2079–87.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kathryn Twigg Arrildt
    • 1
  • Sarah Beth Joseph
    • 2
  • Ronald Swanstrom
    • 3
  1. 1.Department of Microbiology and ImmunologyUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Department of Biochemistry and BiophysicsUniversity of North Carolina at Chapel Hill, CB#7295 Lineberger Comprehensive Cancer CenterChapel HillUSA

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