1887

Abstract

Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3.2 years of infection with simian/human immunodeficiency virus (SHIV)SF162P4cy. A considerable variation in the genetic diversity of proviral quasispecies was present among animals. Seven monkeys exhibited env V1-V2 proviral populations composed of both clusters of identical ancestral sequences and new variants, whereas the other six monkeys displayed relatively high env V1-V2 genetic diversity with a large proportion of diverse novel sequences. Our results demonstrate that in SHIVSF162P4cy-infected monkeys there exists a disparate pattern of intra-host viral diversity and that reseeding of the proviral reservoir occurs in some animals. Moreover, even though no particular association has been observed between MHC haplotypes and the long-term control of infection, a remarkably similar pattern of intra-host viral diversity and divergence was found within animals carrying the M3 haplotype. This suggests that in animals bearing the same MHC haplotype and infected with the same virus, viral diversity follows a similar pattern with similar outcomes and control of infection.

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2018-10-12
2019-10-22
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References

  1. Policicchio BB, Pandrea I, Apetrei C. Animal models for HIV cure research. Front Immunol 2016;7:12 [CrossRef][PubMed]
    [Google Scholar]
  2. Polacino P, Larsen K, Galmin L, Suschak J, Kraft Z et al. Differential pathogenicity of SHIV infection in pig-tailed and rhesus macaques. J Med Primatol 2008;37 Suppl 2:13–23 [CrossRef][PubMed]
    [Google Scholar]
  3. Borsetti A, Baroncelli S, Maggiorella MT, Bellino S, Moretti S et al. Viral outcome of simian-human immunodeficiency virus SHIV-89.6P adapted to cynomolgus monkeys. Arch Virol 2008;153:463–472 [CrossRef][PubMed]
    [Google Scholar]
  4. Veazey RS, Ling B. Short Communication: comparative susceptibility of rhesus macaques of indian and chinese origin to vaginal simian-human immunodeficiency virus transmission as models for HIV prevention research. AIDS Res Hum Retroviruses 2017;33:1199–1201 [CrossRef][PubMed]
    [Google Scholar]
  5. Palesch D, Bosinger SE, Tharp GK, Vanderford TH, Paiardini M et al. Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. Nature 2018;553:77–81 [CrossRef][PubMed]
    [Google Scholar]
  6. Huot N, Bosinger SE, Paiardini M, Reeves RK, Müller-Trutwin M. Lymph node cellular and viral dynamics in natural hosts and impact for HIV cure strategies. Front Immunol 2018;9:780 [CrossRef][PubMed]
    [Google Scholar]
  7. Tan RC, Harouse JM, Gettie A, Cheng-Mayer C. In vivo adaptation of SHIV(SF162): chimeric virus expressing a NSI, CCR5-specific envelope protein. J Med Primatol 1999;28:164–168 [CrossRef][PubMed]
    [Google Scholar]
  8. del Prete GQ, Lifson JD, Keele BF. Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences. Curr Opin HIV AIDS 2016;11:546–554 [CrossRef][PubMed]
    [Google Scholar]
  9. O'Connell KA, Brennan TP, Bailey JR, Ray SC, Siliciano RF et al. Control of HIV-1 in elite suppressors despite ongoing replication and evolution in plasma virus. J Virol 2010;84:7018–7028 [CrossRef][PubMed]
    [Google Scholar]
  10. Rouzioux C, Avettand-Fenoël V. Total HIV DNA: a global marker of HIV persistence. Retrovirology 2018;15:30 [CrossRef][PubMed]
    [Google Scholar]
  11. Salemi M, Rife B. Phylogenetics and phyloanatomy of HIV/SIV intra-host compartments and reservoirs: the key role of the central nervous system. Curr HIV Res 2016;14:110–120 [CrossRef][PubMed]
    [Google Scholar]
  12. Huang SH, Ren Y, Thomas AS, Chan D, Mueller S et al. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells. J Clin Invest 2018;128:876–889 [CrossRef][PubMed]
    [Google Scholar]
  13. de Azevedo SSD, Caetano DG, Côrtes FH, Teixeira SLM, dos Santos Silva K et al. Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers. Retrovirology 2017;14:29 [CrossRef][PubMed]
    [Google Scholar]
  14. Goulder PJ, Watkins DI. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 2008;8:619–630 [CrossRef][PubMed]
    [Google Scholar]
  15. Nomura T, Matano T. Association of MHC-I genotypes with disease progression in HIV/SIV infections. Front Microbiol 2012;3:234 [CrossRef][PubMed]
    [Google Scholar]
  16. Silver ZA, Watkins DI. The role of MHC class I gene products in SIV infection of macaques. Immunogenetics 2017;69:511–519 [CrossRef][PubMed]
    [Google Scholar]
  17. Mee ET, Berry N, Ham C, Aubertin A, Lines J et al. Mhc haplotype M3 is associated with early control of SHIVsbg infection in Mauritian cynomolgus macaques. Tissue Antigens 2010;76:223–229 [CrossRef][PubMed]
    [Google Scholar]
  18. O'Connor SL, Lhost JJ, Becker EA, Detmer AM, Johnson RC et al. MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. Sci Transl Med 2010;2:22ra18 [CrossRef][PubMed]
    [Google Scholar]
  19. Aarnink A, Dereuddre-Bosquet N, Vaslin B, Le Grand R, Winterton P et al. Influence of the MHC genotype on the progression of experimental SIV infection in the Mauritian cynomolgus macaque. Immunogenetics 2011;63:267–274 [CrossRef][PubMed]
    [Google Scholar]
  20. Borsetti A, Maggiorella MT, Sernicola L, Bellino S, Ferrantelli F et al. Influence of MHC class I and II haplotypes on the experimental infection of Mauritian cynomolgus macaques with SHIVSF162P4cy. Tissue Antigens 2012;80:36–45 [CrossRef][PubMed]
    [Google Scholar]
  21. Borsetti A, Ferrantelli F, Maggiorella MT, Sernicola L, Bellino S et al. Effect of MHC haplotype on immune response upon experimental SHIVSF162P4cy infection of Mauritian cynomolgus macaques. PLoS One 2014;9:e93235 [CrossRef][PubMed]
    [Google Scholar]
  22. Seki S, Nomura T, Nishizawa M, Yamamoto H, Ishii H et al. In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts. PLoS Pathog 2017;13:e1006638 [CrossRef][PubMed]
    [Google Scholar]
  23. Kline C, Ndjomou J, Franks T, Kiser R, Coalter V et al. Persistence of viral reservoirs in multiple tissues after antiretroviral therapy suppression in a macaque RT-SHIV model. PLoS One 2013;8:e84275 [CrossRef][PubMed]
    [Google Scholar]
  24. Kearney MF, Anderson EM, Coomer C, Smith L, Shao W et al. Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy. Retrovirology 2015;12:93 [CrossRef][PubMed]
    [Google Scholar]
  25. Matusali G, Dereuddre-Bosquet N, Le Tortorec A, Moreau M, Satie AP et al. Detection of simian immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy. J Virol 2015;89:5772–5787 [CrossRef][PubMed]
    [Google Scholar]
  26. Feder AF, Kline C, Polacino P, Cottrell M, Kashuba ADM et al. A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host. PLoS Pathog 2017;13:e1006358 [CrossRef][PubMed]
    [Google Scholar]
  27. Balfe P, Shapiro S, Hsu M, Buckner C, Harouse JM et al. Expansion of quasispecies diversity but no evidence for adaptive evolution of SHIV during rapid serial transfers among seronegative macaques. Virology 2004;318:267–279 [CrossRef][PubMed]
    [Google Scholar]
  28. Zhang M, Gaschen B, Blay W, Foley B, Haigwood N et al. Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 2004;14:1229–1246 [CrossRef][PubMed]
    [Google Scholar]
  29. Mclaren PJ, Carrington M. The impact of host genetic variation on infection with HIV-1. Nat Immunol 2015;16:577–583 [CrossRef][PubMed]
    [Google Scholar]
  30. Bello G, Casado C, Sandonis V, Alvaro-Cifuentes T, dos Santos CA et al. Plasma viral load threshold for sustaining intrahost HIV type 1 evolution. AIDS Res Hum Retroviruses 2007;23:1242–1250 [CrossRef][PubMed]
    [Google Scholar]
  31. Boritz EA, Darko S, Swaszek L, Wolf G, Wells D et al. Multiple Origins of Virus Persistence during Natural Control of HIV Infection. Cell 2016;166:1004–1015 [CrossRef][PubMed]
    [Google Scholar]
  32. Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K et al. A B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med 2015;21:132–139 [CrossRef][PubMed]
    [Google Scholar]
  33. Seki S, Matano T. CTL Escape and Viral Fitness in HIV/SIV Infection. Front Microbiol 2011;2:267 [CrossRef][PubMed]
    [Google Scholar]
  34. Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R et al. Adaptation of HIV-1 to human leukocyte antigen class I. Nature 2009;458:641–645 [CrossRef][PubMed]
    [Google Scholar]
  35. Loh L, Reece JC, Fernandez CS, Alcantara S, Center R et al. Complexity of the inoculum determines the rate of reversion of SIV Gag CD8 T cell mutant virus and outcome of infection. PLoS Pathog 2009;5:e1000378 [CrossRef][PubMed]
    [Google Scholar]
  36. Huang KH, Goedhals D, Carlson JM, Brockman MA, Mishra S et al. Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations. PLoS One 2011;6:e19018 [CrossRef][PubMed]
    [Google Scholar]
  37. Hsu M, Harouse JM, Gettie A, Buckner C, Blanchard J et al. Increased mucosal transmission but not enhanced pathogenicity of the CCR5-tropic, simian AIDS-inducing simian/human immunodeficiency virus SHIV(SF162P3) maps to envelope gp120. J Virol 2003;77:989–998 [CrossRef][PubMed]
    [Google Scholar]
  38. Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 2007;27:406–416 [CrossRef][PubMed]
    [Google Scholar]
  39. Sutton MS, Ellis-Connell A, Moriarty RV, Balgeman AJ, Gellerup D et al. Acute-phase CD4+ T cell responses targeting invariant viral regions are associated with control of live-attenuated simian immunodeficiency virus. J Virol 2018;87:9353–9364 [CrossRef][PubMed]
    [Google Scholar]
  40. Cain BT, Pham NH, Budde ML, Greene JM, Weinfurter JT et al. T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals. Retrovirology 2013;10:116 [CrossRef][PubMed]
    [Google Scholar]
  41. Rodrigo AG, Goracke PC, Rowhanian K, Mullins JI. Quantitation of target molecules from polymerase chain reaction-based limiting dilution assays. AIDS Res Hum Retroviruses 1997;13:737–742 [CrossRef][PubMed]
    [Google Scholar]
  42. Tsai L, Trunova N, Gettie A, Mohri H, Bohm R et al. Efficient repeated low-dose intravaginal infection with X4 and R5 SHIVs in rhesus macaque: implications for HIV-1 transmission in humans. Virology 2007;362:207–216 [CrossRef][PubMed]
    [Google Scholar]
  43. Varela M, Landskron L, Lai RP, McKinley TJ, Bogers WM et al. Molecular evolution analysis of the human immunodeficiency virus type 1 envelope in simian/human immunodeficiency virus-infected macaques: implications for challenge dose selection. J Virol 2011;85:10332–10345 [CrossRef][PubMed]
    [Google Scholar]
  44. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acid Symp Ser 1999;41:95–98
    [Google Scholar]
  45. Swofford D, Sullivan J. Phylogeny inference based on parsimony and other methods with PAUP*. In Salemi M, Vandamme AM. (editors) The phylogenetic handbook-A practical approach to DNA and protein phylogeny New York: Cambridge University Press; 2003; pp.160–206
    [Google Scholar]
  46. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013;30:2725–2729 [CrossRef][PubMed]
    [Google Scholar]
  47. Slatkin M, Maddison WP. A cladistic measure of gene flow inferred from the phylogenies of alleles. Genetics 1989;123:603–613[PubMed]
    [Google Scholar]
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