1887

Abstract

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of -linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential -linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and -linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.046185-0
2013-01-01
2024-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/1/20.html?itemId=/content/journal/jgv/10.1099/vir.0.046185-0&mimeType=html&fmt=ahah

References

  1. Abebe A., Demissie D., Goudsmit J., Brouwer M., Kuiken C. L., Pollakis G., Schuitemaker H., Fontanet A. L., Rinke de Wit T. F. 1999; HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS. AIDS 13:1305–1311 [View Article][PubMed]
    [Google Scholar]
  2. Altfeld M., Addo M. M., Rosenberg E. S., Hecht F. M., Lee P. K., Vogel M., Yu X. G., Draenert R., Johnston M. N. other authors 2003; Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection. AIDS 17:2581–2591 [View Article][PubMed]
    [Google Scholar]
  3. Anzala O. A., Nagelkerke N. J., Bwayo J. J., Holton D., Moses S., Ngugi E. N., Ndinya-Achola J. O., Plummer F. A. 1995; Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection. J Infect Dis 171:686–689 [View Article][PubMed]
    [Google Scholar]
  4. Biggar R. J., Cassol S., Kumwenda N., Lema V., Janes M., Pilon R., Senzani V., Yellin F., Taha T. E., Broadhead R. L. 2003; The risk of human immunodeficiency virus-1 infection in twin pairs born to infected mothers in Africa. J Infect Dis 188:850–855 [View Article][PubMed]
    [Google Scholar]
  5. Birch M. R., Learmont J. C., Dyer W. B., Deacon N. J., Zaunders J. J., Saksena N., Cunningham A. L., Mills J., Sullivan J. S. 2001; An examination of signs of disease progression in survivors of the Sydney Blood Bank Cohort (SBBC). J Clin Virol 22:263–270 [View Article][PubMed]
    [Google Scholar]
  6. Boom R., Sol C. J. A., Salimans M. M. M., Jansen C. L., Wertheim-van Dillen P. M., van der Noordaa J. 1990; Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495–503[PubMed]
    [Google Scholar]
  7. Borggren M., Repits J., Sterjovski J., Uchtenhagen H., Churchill M. J., Karlsson A., Albert J., Achour A., Gorry P. R. other authors 2011; Increased sensitivity to broadly neutralizing antibodies of end-stage disease R5 HIV-1 correlates with evolution in Env glycosylation and charge. PLoS ONE 6:e20135 [View Article][PubMed]
    [Google Scholar]
  8. Buchbinder S. P., Katz M. H., Hessol N. A., O’Malley P. M., Holmberg S. D. 1994; Long-term HIV-1 infection without immunologic progression. AIDS 8:1123–1128 [View Article][PubMed]
    [Google Scholar]
  9. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. 1995; Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 332:201–208 [View Article][PubMed]
    [Google Scholar]
  10. Carrington M., O’Brien S. J. 2003; The influence of HLA genotype on AIDS. Annu Rev Med 54:535–551 [View Article][PubMed]
    [Google Scholar]
  11. Carrington M., Nelson G. W., Martin M. P., Kissner T., Vlahov D., Goedert J. J., Kaslow R., Buchbinder S., Hoots K., O’Brien S. J. 1999; HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283:1748–1752 [View Article][PubMed]
    [Google Scholar]
  12. Chaillon A., Braibant M., Moreau T., Thenin S., Moreau A., Autran B., Barin F. 2011; The V1V2 domain and an N-linked glycosylation site in the V3 loop of the HIV-1 envelope glycoprotein modulate neutralization sensitivity to the human broadly neutralizing antibody 2G12. J Virol 85:3642–3648 [View Article][PubMed]
    [Google Scholar]
  13. Cho M. W., Lee M. K., Carney M. C., Berson J. F., Doms R. W., Martin M. A. 1998; Identification of determinants on a dualtropic human immunodeficiency virus type 1 envelope glycoprotein that confer usage of CXCR4. J Virol 72:2509–2515[PubMed]
    [Google Scholar]
  14. Deeks S. G., Walker B. D. 2007; Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27:406–416 [View Article][PubMed]
    [Google Scholar]
  15. Draenert R., Allen T. M., Liu Y., Wrin T., Chappey C., Verrill C. L., Sirera G., Eldridge R. L., Lahaie M. P. other authors 2006; Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus. J Exp Med 203:529–539 [View Article][PubMed]
    [Google Scholar]
  16. Easterbrook P. J. 1994; Non-progression in HIV infection. AIDS 8:1179–1182 [View Article][PubMed]
    [Google Scholar]
  17. Gaschen B., Taylor J., Yusim K., Foley B., Gao F., Lang D., Novitsky V., Haynes B., Hahn B. H. other authors 2002; Diversity considerations in HIV-1 vaccine selection. Science 296:2354–2360[PubMed] [CrossRef]
    [Google Scholar]
  18. Hendel H., Caillat-Zucman S., Lebuanec H., Carrington M., O’Brien S., Andrieu J. M., Schächter F., Zagury D., Rappaport J. other authors 1999; New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. J Immunol 162:6942–6946[PubMed]
    [Google Scholar]
  19. Huang Y., Paxton W. A., Wolinsky S. M., Neumann A. U., Zhang L., He T., Kang S., Ceradini D., Jin Z. other authors 1996; The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 2:1240–1243 [View Article][PubMed]
    [Google Scholar]
  20. Hutto C., Zhou Y., He J., Geffin R., Hill M., Scott W., Wood C. 1996; Longitudinal studies of viral sequence, viral phenotype, and immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses. J Virol 70:3589–3598[PubMed]
    [Google Scholar]
  21. Jensen M. A., Li F. S., van ’t Wout A. B., Nickle D. C., Shriner D., He H. X., McLaughlin S., Shankarappa R., Margolick J. B., Mullins J. I. 2003; 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 77:13376–13388 [View Article][PubMed]
    [Google Scholar]
  22. Jere A., Fujita M., Adachi A., Nomaguchi M. 2010; Role of HIV-1 Nef protein for virus replication in vitro. Microbes Infect 12:65–70 [View Article][PubMed]
    [Google Scholar]
  23. Koizumi Y., Kageyama S., Fujiyama Y., Miyashita M., Lwembe R., Ogino K., Shioda T., Ichimura H. 2007; RANTES -28G delays and DC-SIGN - 139C enhances AIDS progression in HIV type 1-infected Japanese hemophiliacs. AIDS Res Hum Retroviruses 23:713–719 [View Article][PubMed]
    [Google Scholar]
  24. Kumar S., Tamura K., Nei M. 2004; mega3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163 [View Article][PubMed]
    [Google Scholar]
  25. Lévy J. A. 1993; HIV pathogenesis and long-term survival. AIDS 7:1401–1410 [View Article][PubMed]
    [Google Scholar]
  26. Liu R., Paxton W. A., Choe S., Ceradini D., Martin S. R., Horuk R., MacDonald M. E., Stuhlmann H., Koup R. A., Landau N. R. 1996; Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367–377 [View Article][PubMed]
    [Google Scholar]
  27. Liu L., Cimbro R., Lusso P., Berger E. A. 2011; Intraprotomer masking of third variable loop (V3) epitopes by the first and second variable loops (V1V2) within the native HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci U S A 108:20148–20153 [View Article][PubMed]
    [Google Scholar]
  28. Margolis L., Shattock R. 2006; Selective transmission of CCR5-utilizing HIV-1: the ‘gatekeeper’ problem resolved?. Nat Rev Microbiol 4:312–317 [View Article][PubMed]
    [Google Scholar]
  29. Mellors J. W., Kingsley L. A., Rinaldo C. R. Jr, Todd J. A., Hoo B. S., Kokka R. P., Gupta P. 1995; Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med 122:573–579[PubMed] [CrossRef]
    [Google Scholar]
  30. Michael N. L., Nelson J. A., KewalRamani V. N., Chang G., O’Brien S. J., Mascola J. R., Volsky B., Louder M., White G. C. II other authors 1998; Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32. J Virol 72:6040–6047[PubMed]
    [Google Scholar]
  31. Morgan D., Mahe C., Mayanja B., Okongo J. M., Lubega R., Whitworth J. A. 2002; HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?. AIDS 16:597–603 [View Article][PubMed]
    [Google Scholar]
  32. Morikita T., Maeda Y., Fujii S., Matsushita S., Obaru K., Takatsuki K. 1997; The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitivity to neutralization by soluble CD4 and cellular tropism. AIDS Res Hum Retroviruses 13:1291–1299 [View Article][PubMed]
    [Google Scholar]
  33. O’Brien S. J., Nelson G. W. 2004; Human genes that limit AIDS. Nat Genet 36:565–574 [View Article][PubMed]
    [Google Scholar]
  34. Paxton W. A., Kang S. 1998; Chemokine receptor allelic polymorphisms: relationships to HIV resistance and disease progression. Semin Immunol 10:187–194 [View Article][PubMed]
    [Google Scholar]
  35. Paxton W. A., Kang S., Liu R., Landau N. R., Gingeras T. R., Wu L., Mackay C. R., Koup R. A. 1999; HIV-1 infectability of CD4+ lymphocytes with relation to betachemokines and the CCR5 coreceptor. Immunol Lett 66:71–75 [View Article][PubMed]
    [Google Scholar]
  36. Pollakis G., Kang S., Kliphuis A., Chalaby M. I., Goudsmit J., Paxton W. A. 2001; N-linked glycosylation of the HIV type-1 gp120 envelope glycoprotein as a major determinant of CCR5 and CXCR4 coreceptor utilization. J Biol Chem 276:13433–13441 [View Article][PubMed]
    [Google Scholar]
  37. Rong R., Gnanakaran S., Decker J. M., Bibollet-Ruche F., Taylor J., Sfakianos J. N., Mokili J. L., Muldoon M., Mulenga J. other authors 2007; Unique mutational patterns in the envelope alpha 2 amphipathic helix and acquisition of length in gp120 hypervariable domains are associated with resistance to autologous neutralization of subtype C human immunodeficiency virus type 1. J Virol 81:5658–5668 [View Article][PubMed]
    [Google Scholar]
  38. Rusert P., Krarup A., Magnus C., Brandenberg O. F., Weber J., Ehlert A. K., Regoes R. R., Günthard H. F., Trkola A. 2011; Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies. J Exp Med 208:1419–1433 [View Article][PubMed]
    [Google Scholar]
  39. Sagar M., Wu X., Lee S., Overbaugh J. 2006; Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol 80:9586–9598 [View Article][PubMed]
    [Google Scholar]
  40. Shankarappa R., Gupta P., Learn G. H. Jr, Rodrigo A. G., Rinaldo C. R. Jr, Gorry M. C., Mullins J. I., Nara P. L., Ehrlich G. D. 1998; Evolution of human immunodeficiency virus type 1 envelope sequences in infected individuals with differing disease progression profiles. Virology 241:251–259 [View Article][PubMed]
    [Google Scholar]
  41. Sheppard H. W., Celum C., Michael N. L., O’Brien S., Dean M., Carrington M., Dondero D., Buchbinder S. P. 2002; HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion. J Acquir Immune Defic Syndr 29:307–313[PubMed] [CrossRef]
    [Google Scholar]
  42. Shieh J. T., Martín J., Baltuch G., Malim M. H., González-Scarano F. 2000; Determinants of syncytium formation in microglia by human immunodeficiency virus type 1: role of the V1/V2 domains. J Virol 74:693–701 [View Article][PubMed]
    [Google Scholar]
  43. Singh K. K., Barroga C. F., Hughes M. D., Chen J., Raskino C., McKinney R. E., Spector S. A. 2003; Genetic influence of CCR5, CCR2, and SDF1 variants on human immunodeficiency virus 1 (HIV-1)-related disease progression and neurological impairment, in children with symptomatic HIV-1 infection. J Infect Dis 188:1461–1472 [View Article][PubMed]
    [Google Scholar]
  44. Tersmette M., Lange J. M., de Goede R. E., de Wolf F., Eeftink-Schattenkerk J. K., Schellekens P. T., Coutinho R. A., Huisman J. G., Goudsmit J., Miedema F. 1989; Association between biological properties of human immunodeficiency virus variants and risk for AIDS and AIDS mortality. Lancet 333:983–985 [View Article][PubMed]
    [Google Scholar]
  45. Tzitzivacos D. B., Tiemessen C. T., Stevens W. S., Papathanasopoulos M. A. 2009; Viral genetic determinants of nonprogressive HIV type 1 subtype C infection in antiretroviral drug-naive children. AIDS Res Hum Retroviruses 25:1141–1148 [View Article][PubMed]
    [Google Scholar]
  46. Wei X., Decker J. M., Wang S., Hui H., Kappes J. C., Wu X., Salazar-Gonzalez J. F., Salazar M. G., Kilby J. M. other authors 2003; Antibody neutralization and escape by HIV-1. Nature 422:307–312 [View Article][PubMed]
    [Google Scholar]
  47. Wu Z., Kayman S. C., Honnen W., Revesz K., Chen H., Vijh-Warrier S., Tilley S. A., McKeating J., Shotton C., Pinter A. 1995; Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. J Virol 69:2271–2278[PubMed]
    [Google Scholar]
  48. Zhang M., Gaschen B., Blay W., Foley B., Haigwood N., Kuiken C., Korber B. 2004; Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14:1229–1246 [View Article][PubMed]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.046185-0
Loading
/content/journal/jgv/10.1099/vir.0.046185-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error