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Is HIV-1 evolving to a less virulent form in humans?

Nature Reviews Microbiology volume 5, pages 141–151 (2007)Cite this article

Abstract

During the rapid spread of HIV-1 in humans, the main (M) group of HIV-1 has evolved into ten distinct subtypes, undergone countless recombination events and diversified extensively. The impact of this extreme genetic diversity on the phenotype of HIV-1 has only recently become a research focus, but early findings indicate that the dominance of HIV-1 subtype C in the current epidemic might be related to the lower virulence of this subtype compared with other subtypes. Here, we explore whether HIV-1 has reached peak virulence or has already started the slow path to attenuation.

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Figure 1: Phylogenetic tree of human and simian lentiviruses.
Figure 2: A hypothetical example of changes in replicative fitness and viral load during HIV-1 disease progression.
Figure 3: HIV-1 diversity in the worldwide epidemic.
Figure 4: Relationship between the increasing prevalence of HIV-1 subtype C and its low pathogenic fitness.

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References

  1. Lemey, P., Pybus, O. G., Van, D. S. & Vandamme, A. M. A Bayesian statistical analysis of human T-cell lymphotropic virus evolutionary rates. Infect. Genet. Evol. 5, 291–298 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Van, D. S., Salemi, M. & Vandamme, A. M. Dating the origin of the African human T-cell lymphotropic virus type-i (HTLV-I) subtypes. Mol. Biol. Evol. 18, 661–671 (2001).

    Article  Google Scholar 

  3. Yoshida, M. Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis. Oncogene 24, 5931–5937 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Coulthart, M. B., Posada, D., Crandall, K. A. & Dekaban, G. A. On the phylogenetic placement of human T cell leukemia virus type 1 sequences associated with an Andean mummy. Infect. Genet. Evol. 6, 91–96 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Korber, B. et al. Timing the ancestor of the HIV-1 pandemic strains. Science 288, 1789–1796 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. UNAIDS/WHO. AIDS Epidemic Update 2006. [online], (UNAIDS/WHO, Geneva, 2006).

  7. Geisbert, T. W. & Jahrling, P. B. Exotic emerging viral diseases: progress and challenges. Nature Med. 10, S110–S121 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Doherty, P. C., Turner, S. J., Webby, R. G. & Thomas, P. G. Influenza and the challenge for immunology. Nature Immunol. 7, 449–455 (2006).

    Article  CAS  Google Scholar 

  9. Perlman, S. & Dandekar, A. A. Immunopathogenesis of coronavirus infections: implications for SARS. Nature Rev. Immunol. 5, 917–927 (2005).

    Article  CAS  Google Scholar 

  10. Gage, K. L. & Kosoy, M. Y. Natural history of plague: perspectives from more than a century of research. Annu. Rev. Entomol. 50, 505–528 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Drancourt, M., Houhamdi, L. & Raoult, D. Yersinia pestis as a telluric, human ectoparasite-borne organism. Lancet Infect. Dis. 6, 234–241 (2006).

    Article  PubMed  Google Scholar 

  12. Fenner, F. & Radcliffe, F. N. Myxomatosis (Cambridge University Press, Cambridge, 1965).

    Google Scholar 

  13. Zuniga, M. C. A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral–host co-adaptation. Virus Res. 88, 17–33 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Best, S. M. & Kerr, P. J. Coevolution of host and virus: the pathogenesis of virulent and attenuated strains of myxoma virus in resistant and susceptible European rabbits. Virology 267, 36–48 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Knell, R. J. Syphilis in renaissance Europe: rapid evolution of an introduced sexually transmitted disease? Proc. Biol. Sci. 271, S174–S176 (2004).

    PubMed  PubMed Central  Google Scholar 

  16. Jin, M. J. et al. Mosaic genome structure of simian immunodeficiency virus from west African green monkeys. EMBO J. 13, 2935–2947 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Apetrei, C., Robertson, D. L. & Marx, P. A. The history of SIVS and AIDS: epidemiology, phylogeny and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa. Front. Biosci. 9, 225–254 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Courgnaud, V. et al. Identification of a new simian immunodeficiency virus lineage with a vpu gene present among different cercopithecus monkeys (C. mona, C. cephus, and C. nictitans) from Cameroon. J. Virol. 77, 12523–12534 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hassel, M. P. The Spatial and Temporal Dynamics of Host-Parasitoid Interactions (Oxford University Press, Oxford, 2000).

    Google Scholar 

  20. Diekmann, O. & Hessterbeek, O. Mathematical Epidemiology of Infectious Diseases: Model Building, Analysis, and Interpretation (Wiley, Chichester, 2006).

    Google Scholar 

  21. Dronamraju, K. R. Infectious Diseases and Host-Pathogen Evolution (Cambridge University Press, Cambridge, 2004).

    Book  Google Scholar 

  22. Anderson, R. M. & May, R. M. Infectious Diseases of Humans: Dynamics and Control (Oxford University Press, Oxford, 1991).

    Google Scholar 

  23. Arts, E. J. & Quinones-Mateu, M. E. Sorting out the complexities of HIV-1 fitness. AIDS 17, 780–781 (2003).

    Article  PubMed  Google Scholar 

  24. Quinones-Mateu, M. E. & Arts, E. J. HIV-1 Fitness: Implications for Drug Resistance, Disease Progression, and Global Epidemic Evolution. [online], (HIV Sequence Compendium, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, 2001).

    Google Scholar 

  25. Feng, J. Y. & Anderson, K. S. Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. Biochemistry 38, 9440–9448 (1999).

    Article  CAS  PubMed  Google Scholar 

  26. Deval, J. et al. Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. J. Biol. Chem. 279, 509–516 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Bull, J. J. Virulence. Evolution 48, 1423–1437 (1994).

    CAS  PubMed  Google Scholar 

  28. Bremermann, H. J. & Pickering, J. A game-theoretical model of parasite virulence. J. Theor. Biol. 100, 411–426 (1983).

    Article  CAS  PubMed  Google Scholar 

  29. Troyer, R. M. et al. Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J. Virol. 79, 9006–9018 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Quinones-Mateu, M. E. et al. A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J. Virol. 74, 9222–9233 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Blaak, H., Brouwer, M., Ran, L. J., de Wolf, F. & Schuitemaker, H. 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, 600–610 (1998).

    Article  CAS  PubMed  Google Scholar 

  32. Barbour, J. D. et al. 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, 251–256 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Ewald, P. W. Evolution of Infectious Disease (Oxford University Press, Oxford, 1994).

    Google Scholar 

  34. Nowak, M. A. & May, R. M. Virus Dynamics: Mathematical Principles of Immunology and Virology (Oxford University Press, Oxford, 2000).

    Google Scholar 

  35. Maynard, S. J. Group selection and kin selection. Nature 201, 1145–1147 (1964).

    Article  Google Scholar 

  36. Szathmary, E. & Maynard, S. J. From replicators to reproducers: the first major transitions leading to life. J. Theor. Biol. 187, 555–571 (1997).

    Article  CAS  PubMed  Google Scholar 

  37. Keele, B. F. et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science 313, 523–526 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gao, F. et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397, 436–441 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Santiago, M. L. et al. SIVcpz in wild chimpanzees. Science 295, 465 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Van Heuverswyn, F. et al. Human immunodeficiency viruses: SIV infection in wild gorillas. Nature 444, 164 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Horimoto, T. & Kawaoka, Y. Influenza: lessons from past pandemics, warnings from current incidents. Nature Rev. Microbiol. 3, 591–600 (2005).

    Article  CAS  Google Scholar 

  42. Hirsch, V. M., Olmsted, R. A., Murphey-Corb, M., Purcell, R. H. & Johnson, P. R. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339, 389–392 (1989).

    Article  CAS  PubMed  Google Scholar 

  43. Lemey, P. et al. Tracing the origin and history of the HIV-2 epidemic. Proc. Natl Acad. Sci. USA 100, 6588–6592 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schim van der Loeff, M. F. & Aaby, P. Towards a better understanding of the epidemiology of HIV-2. AIDS 13, S69–S84 (1999).

    Google Scholar 

  45. Schim van der Loeff, M. F. et al. Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2. Int. J. Epidemiol. 35, 1322–1328 (2006).

    Article  PubMed  Google Scholar 

  46. Ayouba, A. et al. HIV-1 group O infection in Cameroon, 1986 to 1998. Emerg. Infect. Dis. 7, 466–467 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yamaguchi, J. et al. HIV infections in northwestern Cameroon: identification of HIV type 1 group O and dual HIV type 1 group M and group O infections. AIDS Res. Hum. Retroviruses 20, 944–957 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Yamaguchi, J. et al. HIV-1 Group N: evidence of ongoing transmission in Cameroon. AIDS Res. Hum. Retroviruses 22, 453–457 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Yamaguchi, J. et al. Identification of HIV type 1 group N infections in a husband and wife in Cameroon: viral genome sequences provide evidence for horizontal transmission. AIDS Res. Hum. Retroviruses 22, 83–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Salemi, M. et al. Dating the common ancestor of SIVcpz and HIV-1 group M and the origin of HIV-1 subtypes using a new method to uncover clock-like molecular evolution. FASEB J. 15, 276–278 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Travers, S. A. et al. Timing and reconstruction of the most recent common ancestor of the subtype C clade of human immunodeficiency virus type 1. J. Virol. 78, 10501–10506 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Arien, K. K. et al. The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates. J. Virol. 79, 8979–8990 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ball, S. C. et al. Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C. J. Virol. 77, 1021–1038 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Barnett, S. W., Quiroga, M., Werner, A., Dina, D. & Levy, J. A. Distinguishing features of an infectious molecular clone of the highly divergent and noncytopathic human immunodeficiency virus type 2 UC1 strain. J. Virol. 67, 1006–1014 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Talbott, R., Kraus, G., Looney, D. & Wong-Staal, F. Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity. Proc. Natl Acad. Sci. USA 90, 4226–4230 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pollakis, G. et al. Phenotypic and genotypic comparisons of CCR5- and CXCR4-tropic human immunodeficiency virus type 1 biological clones isolated from subtype C-infected individuals. J. Virol. 78, 2841–2852 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Curran, J. W. et al. Epidemiology of HIV infection and AIDS in the United States. Science 239, 610–616 (1988).

    Article  CAS  PubMed  Google Scholar 

  58. Parazzini, F. et al. Number of sexual partners, condom use and risk of human immunodeficiency virus infection. Int. J. Epidemiol. 24, 1197–1203 (1995).

    Article  CAS  PubMed  Google Scholar 

  59. Ryder, R. W. & Behets, F. Reasons for the wide variation in reported rates of mother-to-child transmission of HIV-1. AIDS 8, 1495–1497 (1994).

    Article  CAS  PubMed  Google Scholar 

  60. Gray, R. H. et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 357, 1149–1153 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Quinn, T. C. et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N. Engl. J Med. 342, 921–929 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Garcia, P. M. et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N. Engl. J Med. 341, 394–402 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Shankarappa, R. et al. Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J. Virol. 73, 10489–10502 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhu, T. et al. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261, 1179–1181 (1993).

    Article  CAS  PubMed  Google Scholar 

  65. Shattock, R. J. & Moore, J. P. Inhibiting sexual transmission of HIV-1 infection. Nature Rev. Microbiol. 1, 25–34 (2003).

    Article  CAS  Google Scholar 

  66. Shattock, R. J., Griffin, G. E. & Gorodeski, G. I. In vitro models of mucosal HIV transmission. Nature Med. 6, 607–608 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Bergstrom, C. T., McElhany, P. & Real, L. A. Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens. Proc. Natl Acad. Sci. USA 96, 5095–5100 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lazaro, E., Escarmis, C., Perez-Mercader, J., Manrubia, S. C. & Domingo, E. Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss. Proc. Natl Acad. Sci. USA 100, 10830–10835 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Elena, S. F. et al. Evolution of fitness in experimental populations of vesicular stomatitis virus. Genetics 142, 673–679 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sagar, M. et al. Infection with multiple human immunodeficiency virus type 1 variants is associated with faster disease progression. J. Virol. 77, 12921–12926 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pontesilli, O. et al. 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, 1008–1018 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Dyer, W. B. et al. 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, 436–443 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cao, Y., Qin, L., Zhang, L., Safrit, J. & Ho, D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N. Eng. J. Med. 332, 201–208 (1995).

    Article  CAS  Google Scholar 

  74. Pantaleo, G. et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N. Eng. J. Med. 332, 209–216 (1995).

    Article  CAS  Google Scholar 

  75. Montefiori, D. C. et al. Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors. J. Infect. Dis. 173, 60–67 (1996).

    Article  CAS  PubMed  Google Scholar 

  76. Carotenuto, P., Looij, D., Keldermans, L., de Wolf, F. & Goudsmit, J. Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection. AIDS 12, 1591–1600 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Rosenberg, E. S. et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447–1450 (1997).

    Article  CAS  PubMed  Google Scholar 

  78. Dean, M. et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273, 1856–1862 (1996).

    Article  CAS  PubMed  Google Scholar 

  79. Berger, E. A., Murphy, P. M. & Farber, J. M. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657–700 (1999).

    Article  CAS  PubMed  Google Scholar 

  80. Gonzalez, E. et al. Global survey of genetic variation in CCR5, RANTES, and MIP-1α: impact on the epidemiology of the HIV-1 pandemic. Proc. Natl Acad. Sci. USA 98, 5199–5204 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gonzalez, E. et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 1434–1440 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. McDermott, D. H. et al. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352, 866–870 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Mellors, J. W. et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272, 1167–1170 (1996).

    Article  CAS  PubMed  Google Scholar 

  84. Collier, A. C. et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N. Engl. J. Med. 334, 1011–1017 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Silvestri, G. et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity. 18, 441–452 (2003).

    Article  CAS  PubMed  Google Scholar 

  86. Rodriguez, B. et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296, 1498–1506 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. Deacon, N. J. et al. Genomic structure of an attenuated quasispecies of HIV-1 from a blood transfusion donor and recipients. Science 270, 988–991 (1995).

    Article  CAS  PubMed  Google Scholar 

  88. Kirchhoff, F., Greenough, T. C., Brettler, D. B., Sullivan, J. L. & Desrosiers, R. C. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Eng. J. Med. 332, 228–232 (1995).

    Article  CAS  Google Scholar 

  89. Huang, Y., Zhang, l. & Ho, D. D. Biological characterization of nef in long-term survivors of human immunodeficiency virus type 1 infection. J. Virol. 69, 8142–8146 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Leroux, C., Issel, C. J. & Montelaro, R. C. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J. Virol. 71, 9627–9639 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Plagemann, P. G., Chen, Z. & Li, K. Replication competition between lactate dehydrogenase-elevating virus quasispecies in mice. Implications for quasispecies selection and evolution. Arch. Virol. 146, 1283–1296 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Lu, J. & Kuritzkes, D. R. A novel recombinant marker virus assay for comparing the relative fitness of hiv-1 reverse transcriptase variants. J. Acquir. Immune. Defic. Syndr. 27, 7–13 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Holland, J. J., de la Torre, J. C., Clarke, D. K. & Duarte, E. Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J. Virol. 65, 2960–2967 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Domingo, E., Escarmis, C., Menendez-Arias, L. & Holland, J. in Origin And Evolution of Viruses (eds Domingo, E., Webster, R. & Holland, J.) 141–161 (Academic Press, San Diego, 1999).

    Book  Google Scholar 

  95. Harrigan, P. R., Bloor, S. & Larder, B. A. Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. J. Virol. 72, 3773–3778 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Quinones-Mateu, M. E. & Arts, E. J. Virus fitness: concept, quantification, and application to HIV population dynamics. Curr. Top. Microbiol. Immunol. 299, 83–140 (2006).

    CAS  PubMed  Google Scholar 

  97. Clarke, D. K. et al. The red queen reigns in the kingdom of RNA viruses. Proc. Natl Acad. Sci. USA 91, 4821–4824 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Novella, I. S. et al. Exponential increases of RNA virus fitness during large population transmissions. Proc. Natl Acad. Sci. USA 92, 5841–5844 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Chao, L. Fitness of RNA virus decreased by Muller's ratchet. Nature 348, 454–455 (1990).

    Article  CAS  PubMed  Google Scholar 

  100. Domingo, E. & Holland, J. J. RNA virus mutations and fitness for survival. Annu. Rev. Microbiol. 51, 151–178 (1997).

    Article  CAS  PubMed  Google Scholar 

  101. Yuste, E., Sanchez-Palomino, S., Casado, C., Domingo, E. & Lopez-Galindez, C. Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events. J. Virol. 73, 2745–2751 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mullins, J. I. & Jensen, M. A. Evolutionary dynamics of HIV-1 and the control of AIDS. Curr. Top. Microbiol. Immunol. 299, 171–192 (2006).

    CAS  PubMed  Google Scholar 

  103. Wei, X. et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117–122 (1995).

    Article  CAS  PubMed  Google Scholar 

  104. Betts, M. R. et al. Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses: relationship to viral load in untreated HIV infection. J. Virol. 75, 11983–11991 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Rosenberg, E. S. et al. Immune control of HIV-1 after early treatment of acute infection. Nature 407, 523–526 (2000).

    Article  CAS  PubMed  Google Scholar 

  106. Goulder, P. J. et al. Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection. J. Exp. Med. 193, 181–194 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Goulder, P. J. & Watkins, D. I. HIV and SIV CTL escape: implications for vaccine design. Nature Rev. Immunol. 4, 630–640 (2004).

    Article  CAS  Google Scholar 

  108. Cao, K. et al. Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci. Tissue Antigens 63, 293–325 (2004).

    Article  CAS  PubMed  Google Scholar 

  109. Moore, C. B. et al. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296, 1439–1443 (2002).

    Article  CAS  PubMed  Google Scholar 

  110. Goulder, P. J. et al. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412, 334–338 (2001).

    Article  CAS  PubMed  Google Scholar 

  111. Leslie, A. J. et al. HIV evolution: CTL escape mutation and reversion after transmission. Nature Med. 10, 282–289 (2004).

    Article  CAS  PubMed  Google Scholar 

  112. Martinez-Picado, J. et al. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J. Virol. 80, 3617–3623 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Troyer, R. M. et al. The fitness cost of CTL escape: not a terrible hardship on HIV-1? [online], (XVI International AIDS Conference, Toronto, Canada 13–18 August, 2006)

  114. Sheehy, A. M., Gaddis, N. C., Choi, J. D. & Malim, M. H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646–650 (2002).

    Article  CAS  PubMed  Google Scholar 

  115. Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Markowitz, M. et al. Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report. Lancet 365, 1031–1038 (2005).

    Article  PubMed  Google Scholar 

  117. Van de, P. P. Viral and host determinants of HIV-1 pathogenesis. AIDS 20, 933–934 (2006).

    Article  Google Scholar 

  118. Muller, V. & De Boer, R. J. The integration hypothesis: an evolutionary pathway to benign SIV infection. PLoS Pathog. 2, e15 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Muller, V. et al. Stable virulence levels in the HIV epidemic of Switzerland over two decades. AIDS 20, 889–894 (2006).

    Article  PubMed  Google Scholar 

  120. Kannangara, S., DeSimone, J. A. & Pomerantz, R. J. Attenuation of HIV-1 infection by other microbial agents. J. Infect. Dis. 192, 1003–1009 (2005).

    Article  PubMed  Google Scholar 

  121. Arien, K. K. et al. Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time. AIDS 19, 1555–1564 (2005).

    Article  PubMed  Google Scholar 

  122. Yerly, S. et al. Transmission of antiretroviral-drug-resistant HIV-1 variants. Lancet 354, 729–733 (1999).

    Article  CAS  PubMed  Google Scholar 

  123. Turner, D. & Wainberg, M. A. HIV transmission and primary drug resistance. AIDS Rev. 8, 17–23 (2006).

    PubMed  Google Scholar 

  124. Eyster, M. E. Test may predict which patients with HIV infection will develop AIDS. Am. Fam. Physician 39, 276 (1989).

    CAS  PubMed  Google Scholar 

  125. McCune, J. M. The dynamics of CD4+ T-cell depletion in HIV disease. Nature 410, 974–979 (2001).

    Article  CAS  PubMed  Google Scholar 

  126. Marlink, R. et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 265, 1587–1590 (1994).

    Article  CAS  PubMed  Google Scholar 

  127. Matheron, S. et al. Factors associated with clinical progression in HIV-2 infected-patients: The French ANRS cohort. AIDS 17, 2593–2601 (2003).

    Article  PubMed  Google Scholar 

  128. Gilbert, P. B. et al. Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal. Stat. Med. 22, 573–593 (2003).

    Article  PubMed  Google Scholar 

  129. Kanki, P. J. et al. Slower heterosexual spread of HIV-2 than HIV-1. Lancet 343, 943–946 (1994).

    Article  CAS  PubMed  Google Scholar 

  130. Essex, M. Human immunodeficiency viruses in the developing world. Adv. Virus Res. 53, 71–88 (1999).

    Article  CAS  PubMed  Google Scholar 

  131. Luo, C. C. et al. HIV-1 subtype C in China. Lancet 345, 1051–1052 (1995).

    Article  CAS  PubMed  Google Scholar 

  132. Piyasirisilp, S. et al. 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, 11286–11295 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Soares, E. A. et al. HIV-1 subtype C dissemination in southern Brazil. AIDS 19, S81–S86 (2005).

    Article  PubMed  Google Scholar 

  134. Vidal, N. et al. Distribution of HIV-1 variants in the Democratic Republic of Congo suggests increase of subtype C in Kinshasa between 1997 and 2002. J. Acquir. Immune. Defic. Syndr. 40, 456–462 (2005).

    Article  PubMed  Google Scholar 

  135. Walker, P. R., Pybus, O. G., Rambaut, A. & Holmes, E. C. Comparative population dynamics of HIV-1 subtypes B and C: subtype-specific differences in patterns of epidemic growth. Infect. Genet. Evol. 5, 199–208 (2005).

    Article  CAS  PubMed  Google Scholar 

  136. Renjifo, B. et al. Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes. J. Hum. Virol. 4, 16–25 (2001).

    CAS  PubMed  Google Scholar 

  137. Renjifo, B. et al. Preferential in utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 18, 1629–1636 (2004).

    Article  CAS  PubMed  Google Scholar 

  138. Yang, C. et al. Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission. AIDS 17, 1667–1674 (2003).

    Article  PubMed  Google Scholar 

  139. Eshleman, S. H. et al. Comparison of mother-to-child transmission rates in Ugandan women with subtype A versus D HIV-1 who received single-dose nevirapine prophylaxis. HIV Network For Prevention Trials 012. J. Acquir. Immune. Defic. Syndr. 39, 593–597 (2005).

    PubMed  Google Scholar 

  140. Pope, M. et al. Human immunodeficiency virus type 1 strains of subtypes B and E replicate in cutaneous dendritic cell-T-cell mixtures without displaying subtype-specific tropism. J. Virol. 71, 8001–8007 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Dittmar, M. T. et al. Langerhans cell tropism of human immunodeficiency virus type 1 subtype A through F isolates derived from different transmission groups. J. Virol. 71, 8008–8013 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Tovanabutra, S. et al. The changing molecular epidemiology of HIV type 1 among northern Thai drug users, 1999 to 2002. AIDS Res. Hum. Retroviruses 20, 465–475 (2004).

    Article  CAS  PubMed  Google Scholar 

  143. Zaitseva, M. et al. Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection. Nature Med. 3, 1369–1375 (1997).

    Article  CAS  PubMed  Google Scholar 

  144. Arien, K. K. et al. The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates. J. Virol. 79, 8979–8990 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Johnston, E. R. et al. High frequency of syncytium-inducing and CXCR4-tropic viruses among human immunodeficiency virus type 1 subtype C-infected patients receiving antiretroviral treatment. J. Virol. 77, 7682–7688 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Gupta, S., Anderson, R. M. & May, R. M. Networks of sexual contacts: implications for the pattern of spread of HIV. AIDS 3, 807–817 (1989).

    Article  CAS  PubMed  Google Scholar 

  147. Anderson, R. M., Ng, T. W., Boily, M. C. & May, R. M. The influence of different sexual-contact patterns between age classes on the predicted demographic impact of AIDS in developing countries. Ann. N. Y. Acad. Sci. 569, 240–274 (1989).

    Article  CAS  PubMed  Google Scholar 

  148. Pilcher, C. D., Eron, J. J. Jr, Galvin, S., Gay, C. & Cohen, M. S. Acute HIV revisited: new opportunities for treatment and prevention. J. Clin. Invest. 113, 937–945 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Jacquez, J. A., Koopman, J. S., Simon, C. P. & Longini, I. M. Jr. Role of the primary infection in epidemics of HIV infection in gay cohorts. J. Acquir. Immune. Defic. Syndr. 7, 1169–1184 (1994).

    CAS  PubMed  Google Scholar 

  150. Koopman, J. S. et al. The role of early HIV infection in the spread of HIV through populations. J. Acquir. Immune. Defic. Syndr. Hum. Retrovirol. 14, 249–258 (1997).

    Article  CAS  PubMed  Google Scholar 

  151. Ndung'u, T. et al. Infectious simian/human immunodeficiency virus with human immunodeficiency virus type 1 subtype C from an African isolate: rhesus macaque model. J. Virol. 75, 11417–11425 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Gray, C. M. et al. Viral dynamics and CD4+ T cell counts in subtype C human immunodeficiency virus type 1-infected individuals from southern Africa. AIDS Res. Hum. Retroviruses 21, 285–291 (2005).

    Article  CAS  PubMed  Google Scholar 

  153. Neilson, J. R. et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya. J. Virol. 73, 4393–4403 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Kaleebu, P. et al. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda. J. Infect. Dis. 185, 1244–1250 (2002).

    Article  PubMed  Google Scholar 

  155. Vasan, A. et al. Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin. Infect. Dis. 42, 843–852 (2006).

    Article  PubMed  Google Scholar 

  156. Kaleebu, P. et al. Relationship between HIV-1 Env subtypes A and D and disease progression in a rural Ugandan cohort. AIDS 15, 293–299 (2001).

    Article  CAS  PubMed  Google Scholar 

  157. Choge, I. et al. Genotypic and phenotypic characterization of viral isolates from HIV-1 subtype C-infected children with slow and rapid disease progression. AIDS Res. Hum. Retroviruses 22, 458–465 (2006).

    Article  CAS  PubMed  Google Scholar 

  158. Senkaali, D. et al. The relationship between HIV type 1 disease progression and V3 serotype in a rural Ugandan cohort. AIDS Res. Hum. Retroviruses 20, 932–937 (2004).

    Article  PubMed  Google Scholar 

  159. Arts, E. J. et al. Infection with subtype C HIV-1 of lower replicative fitness as compared to subtypes A and D leads to slower disease progression in Zimbabwean and Ugandan women. [online], (XVI International AIDS Conference, Toronto, Canada 13–18 August, 2006).

  160. Pierson, T., McArthur, J. & Siliciano, R. F. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu. Rev. Immunol. 18, 665–708 (2000).

    Article  CAS  PubMed  Google Scholar 

  161. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).

    Article  CAS  PubMed  Google Scholar 

  162. Li, D. Q., Zheng, X. W. & Zhang, G. Y. Study on the distribution HIV-1 C subtype in Ruili and other counties, Yunnan, China (Translation). Zhonghua Liu Xing. Bing. Xue. Za Zhi. 17, 337–339 (1996).

    CAS  PubMed  Google Scholar 

  163. Li, X. J. et al. Molecular epidemiology of the heterosexual HIV-1 transmission in Kunming, Yunnan Province of China suggests origin from the local IDU epidemic. AIDS Res. Hum. Retroviruses 21, 977–980 (2005).

    Article  CAS  PubMed  Google Scholar 

  164. Van Harmelen, J. H. et al. A predominantly HIV type 1 subtype C-restricted epidemic in South African urban populations. AIDS Res. Hum. Retroviruses 15, 395–398 (1999).

    Article  CAS  PubMed  Google Scholar 

  165. Rainwater, S. et al. No evidence for rapid subtype c spread within an epidemic in which multiple subtypes and intersubtype recombinants circulate. AIDS Res. Hum. Retroviruses 21, 1060–1065 (2005).

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Miguel Quinones-Mateu, Luc Kestens, Robert Colebunders and Guido van der Groen for their helpful suggestions in the development of these attenuation hypotheses. We also thank Aslam Syed and Lora Angelova in the Arts laboratory for their contributions to the supplementary data.

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  1. Kevin K. Ariën

    Present address: the Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, Ghent, B-9000, Belgium

Authors and Affiliations

  1. the Department of Microbiology, HIV and Retrovirology Research Unit, Institute of Tropical Medicine, Nationalestraat 155, Antwerp, B2000, Belgium

    Kevin K. Ariën & Guido Vanham

  2. the Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 2109, Adelbert Rd, Cleveland, 44195, Ohio, USA

    Eric J. Arts

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Ariën, K., Vanham, G. & Arts, E. Is HIV-1 evolving to a less virulent form in humans?. Nat Rev Microbiol 5, 141–151 (2007). https://doi.org/10.1038/nrmicro1594

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