1887

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Volume 86, Issue 12

Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation Free

Abstract

To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serum–virus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells μl. Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.

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2005-12-01
2024-04-23
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References

  1. Albert J., Bredberg U., Chiodi F., Böttiger B., Fenyö E. M., Norrby E., Biberfeld G. 1987; A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II, and HTLV-IIIB. AIDS Res Hum Retroviruses 3:3–10 [CrossRef]
     [Google Scholar]
  2. Albert J., Abrahamsson B., Nagy K., Aurelius E., Gaines H., Nyström G., Fenyö E. M. 1990; Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4:107–112 [CrossRef]
     [Google Scholar]
  3. Albert J., Stalhandske P., Marquina S., Karis J., Fouchier R. A., Norrby E., Chiodi F. 1996; Biological phenotype of HIV type 2 isolates correlates with V3 genotype. AIDS Res Hum Retroviruses 12:821–828 [CrossRef]
     [Google Scholar]
  4. Andersson S. 2001; HIV-2 and the immune response. AIDS Rev 3:11–23
     [Google Scholar]
  5. Andersson S., Norrgren H., da Silva Z., Biague A., Bamba S., Kwok S., Christopherson C., Biberfeld G., Albert J. 2000; Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection. Arch Intern Med 160:3286–3293 [CrossRef]
     [Google Scholar]
  6. Andreasson P. A., Dias F., Naucler A., Andersson S., Biberfeld G. 1993; A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau. AIDS 7:989–993 [CrossRef]
     [Google Scholar]
  7. Ariyoshi K., Harwood E., Chiengsong-Popov R., Weber J. 1992; Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies?. Lancet 340:1257–1258 [CrossRef]
     [Google Scholar]
  8. Åsjö B., Morfeldt-Månsson L., Albert J., Biberfeld G., Karlsson A., Lidman K., Fenyö E. M. 1986; Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet ii:660–662
     [Google Scholar]
  9. Benjouad A., Gluckman J.-C., Rochat H., Montagnier L., Bahraoui E. 1992; Influence of carbohydrate moieties on the immunogenicity of human immunodeficiency virus type 1 recombinant gp160. J Virol 66:2473–2483
     [Google Scholar]
  10. Berry N., Ariyoshi K., Jaffar S., Sabally S., Corrah T., Tedder R., Whittle H. 1998; Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection. J Hum Virol 1:457–468
     [Google Scholar]
  11. Björling E., Scarlatti G., von Gegerfelt A., Albert J., Biberfeld G., Chiodi F., Norrby E., Fenyö E. M. 1993; Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. Virology 193:528–530 [CrossRef]
     [Google Scholar]
  12. Björndal A., Deng H., Jansson M. 7 other authors 1997; Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 71:7478–7487
     [Google Scholar]
  13. Blaak H., Boers P. H. M., Gruters R. A., Schuitemaker H., van der Ende M. E., Osterhaus A. D. M. E. 2005; CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia. J Virol 79:1686–1700 [CrossRef]
     [Google Scholar]
  14. Brandin E., Lindborg L., Gyllensten K., Brostrom C., Hagberg L., Gisslen M., Tuvesson B., Blaxhult A., Albert J. 2003; pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy. AIDS Res Hum Retroviruses 19:543–550 [CrossRef]
     [Google Scholar]
  15. Carotenuto P., Looij D., Keldermans L., de Wolf F., Goudsmit J. 1998; Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection. AIDS 12:1591–1600 [CrossRef]
     [Google Scholar]
  16. CDC 1992; 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 41:1–19
     [Google Scholar]
  17. Chackerian B., Rudensey L. M., Overbaugh J. 1997; Specific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies. J Virol 71:7719–7727
     [Google Scholar]
  18. Clapham P. R., McKnight á., Weiss R. A. 1992; Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4. J Virol 66:3531–3537
     [Google Scholar]
  19. Connor R. I., Sheridan K. E., Ceradini D., Choe S., Landau N. R. 1997; Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185:621–628 [CrossRef]
     [Google Scholar]
  20. De Jong J.-J., De Ronde A., Keulen W., Tersmette M., Goudsmit J. 1992; Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol 66:6777–6780
     [Google Scholar]
  21. Derdeyn C. A., Decker J. M., Bibollet-Ruche F. 11 other authors 2004; Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022 [CrossRef]
     [Google Scholar]
  22. Dreyer K., Kallas E. G., Planelles V., Montefiori D., McDermott M. P., Hasan M. S., Evans T. G. 1999; Primary isolate neutralization by HIV type 1-infected patient sera in the era of highly active antiretroviral therapy. AIDS Res Hum Retroviruses 15:1563–1571 [CrossRef]
     [Google Scholar]
  23. Fenyö E. M., Putkonen P. 1996; Broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections. Immunol Lett 51:95–99 [CrossRef]
     [Google Scholar]
  24. Fouchier R. A. M., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., Miedema F., Schuitemaker H. 1992; Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol 66:3183–3187
     [Google Scholar]
  25. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J. Jr, Gajdusek D. C. 1988; Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A 85:4478–4482 [CrossRef]
     [Google Scholar]
  26. Goulder P. J. R., Brander C., Tang Y. 16 other authors 2001; Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412:334–338 [CrossRef]
     [Google Scholar]
  27. Hall T. A. 1999; BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98
     [Google Scholar]
  28. Homsy J., Meyer M., Levy J. A. 1990; Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol 64:1437–1440
     [Google Scholar]
  29. Isaka Y., Sato A., Miki S. 8 other authors 1999; Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5. Virology 264:237–243 [CrossRef]
     [Google Scholar]
  30. Javaherian K., Langlois A. J., McDanal C. 8 other authors 1989; Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A 86:6768–6772 [CrossRef]
     [Google Scholar]
  31. Jaye A., Sarge-Njie R., van der Loeff M. S., Todd J., Alabi A., Sabally S., Corrah T., Whittle H. 2004; No differences in cellular immune responses between asymptomatic HIV type 1- and type 2-infected Gambian patients. J Infect Dis 189:498–505 [CrossRef]
     [Google Scholar]
  32. Kanki P. J., Travers K. U., Mboup S. 9 other authors 1994; Slower heterosexual spread of HIV-2 than HIV-1. Lancet 343:943–946 [CrossRef]
     [Google Scholar]
  33. Karlsson I., Antonsson L., Shi Y., Karlsson A., Albert J., Leitner T., Olde B., Owman C., Fenyö E. M. 2003; HIV biological variability unveiled: frequent isolations and chimeric receptors reveal unprecedented variation of coreceptor use. AIDS 17:2561–2569 [CrossRef]
     [Google Scholar]
  34. Kimura M. 1980; A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120 [CrossRef]
     [Google Scholar]
  35. Koot M., Keet I. P. M., Vos A. H. V., de Goede R. E. Y., Roos M. T. L., Coutinho R. A., Miedema F., Schellekens P. T. A., Tersmette M. 1993; Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 118:681–688 [CrossRef]
     [Google Scholar]
  36. Kumar S., Tamura K., Jakobsen I. B., Nei M. 2001; mega2: molecular evolutionary genetic analysis software. Bioinformatics 17:1244–1245 [CrossRef]
     [Google Scholar]
  37. Marlink R., Kanki P., Thior I. 13 other authors 1994; Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 265:1587–1590 [CrossRef]
     [Google Scholar]
  38. McCaffrey R. A., Saunders C., Hensel M., Stamatatos L. 2004; N-linked glycosylation of the V3 loop and the immunologically silent face of gp120 protects human immunodeficiency virus type 1 SF162 from neutralization by anti-gp120 and anti-gp41 antibodies. J Virol 78:3279–3295 [CrossRef]
     [Google Scholar]
  39. McKnight á., Shotton C., Cordell J., Jones I., Simmons G., Clapham P. R. 1996; Location, exposure, and conservation of neutralizing and nonneutralizing epitopes on human immunodeficiency virus type 2 SU glycoprotein. J Virol 70:4598–4606
     [Google Scholar]
  40. McKnight á., Dittmar M. T., Moniz-Periera J. 8 other authors 1998; A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4. J Virol 72:4065–4071
     [Google Scholar]
  41. Mörner A., Achour A., Norin M., Thorstensson R., Björling E. 1999a; Fine characterization of a V3-region neutralizing epitope in human immunodeficiency virus type 2. Virus Res 59:49–60 [CrossRef]
     [Google Scholar]
  42. Mörner A., Björndal Å., Albert J., KewalRamani V. N., Littman D. R., Inoue R., Thorstensson R., Fenyö E. M., Björling E. 1999b; Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J Virol 73:2343–2349
     [Google Scholar]
  43. Mörner A., Björndal Å., Leandersson A.-C., Albert J., Björling E., Jansson M. 2002; CCR5 or CXCR4 is required for efficient infection of peripheral blood mononuclear cells by promiscuous human immunodeficiency virus type 2 primary isolates. AIDS Res Hum Retroviruses 18:193–200 [CrossRef]
     [Google Scholar]
  44. Nabatov A. A., Pollakis G., Linnemann T., Kliphius A., Chalaby M. I. M., Paxton W. A. 2004; Intrapatient alterations in the human immunodeficiency virus type 1 gp120 V1V2 and V3 regions differentially modulate coreceptor usage, virus inhibition by CC/CXC chemokines, soluble CD4, and the b12 and 2G12 monoclonal antibodies. J Virol 78:524–530 [CrossRef]
     [Google Scholar]
  45. Ogert R. A., Lee M. K., Ross W., Buckler-White A., Martin M. A., Cho M. W. 2001; N-linked glycosylation sites adjacent to and within the V1/V2 and the V3 loops of dualtropic human immunodeficiency virus type 1 isolate DH12 gp120 affect coreceptor usage and cellular tropism. J Virol 75:5998–6006 [CrossRef]
     [Google Scholar]
  46. Pepin J., Morgan G., Dunn D., Gevao S., Mendy M., Gaye I., Scollen N., Tedder R., Whittle H. 1991; HIV-2-induced immunosuppression among asymptomatic West African prostitutes: evidence that HIV-2 is pathogenic, but less so than HIV-1. AIDS 5:1165–1172 [CrossRef]
     [Google Scholar]
  47. Pollakis G., Kang S., Kliphuis A., Chalaby M. I. M., 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 [CrossRef]
     [Google Scholar]
  48. Polzer S., Dittmar M. T., Schmitz H., Schreiber M. 2002; The N-linked glycan g15 within the V3 loop of the HIV-1 external glycoprotein gp120 affects coreceptor usage, cellular tropism, and neutralization. Virology 304:70–80 [CrossRef]
     [Google Scholar]
  49. Popper S. J., Sarr A. D., Travers K. U., Guèye-Ndiaye A., Mboup S., Essex M. E., Kanki P. J. 1999; Lower human immunodeficiency virus (HIV) type 2 viral load reflects the difference in pathogenicity of HIV-1 and HIV-2. J Infect Dis 180:1116–1121 [CrossRef]
     [Google Scholar]
  50. Reeves J. D., Doms R. W. 2002; Human immunodeficiency virus type 2. J Gen Virol 83:1253–1265
     [Google Scholar]
  51. Reeves J. D., Hibbitts S., Simmons G., McKnight á., Azevedo-Pereira J. M., Moniz-Pereira J., Clapham P. R. 1999; Primary human immunodeficiency virus type 2 (HIV-2) isolates infect CD4-negative cells via CCR5 and CXCR4: comparison with HIV-1 and simian immunodeficiency virus and relevance to cell tropism in vivo. J Virol 73:7795–7804
     [Google Scholar]
  52. Richman D. D., Wrin T., Little S. J., Petropoulos C. J. 2003; Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 100:4144–4149 [CrossRef]
     [Google Scholar]
  53. Rucker J., Edinger A. L., Sharron M. 9 other authors 1997; Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses. J Virol 71:8999–9007
     [Google Scholar]
  54. Rusche J. R., Javaherian K., McDanal C. 10 other authors 1988; Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A 85:3198–3202 [CrossRef]
     [Google Scholar]
  55. Rybarczyk B. J., Montefiori D., Johnson P. R., West A., Johnston R. E., Swanstrom R. 2004; Correlation between env V1/V2 region diversification and neutralizing antibodies during primary infection by simian immunodeficiency virus sm in rhesus macaques. J Virol 78:3561–3571 [CrossRef]
     [Google Scholar]
  56. Saitou N., Nei M. 1987; The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
     [Google Scholar]
  57. Scarlatti G., Albert J., Rossi P., Hodara V., Biraghi P., Muggiasca L., Fenyö E. M. 1993; Mother-to-child transmission of human immunodeficiency virus type 1: correlation with neutralizing antibodies against primary isolates. J Infect Dis 168:207–210 [CrossRef]
     [Google Scholar]
  58. Schønning K., Jansson B., Olofsson S., Nielsen J. O., Hansen J.-E. S. 1996; Resistance to V3-directed neutralization caused by an N-linked oligosaccharide depends on the quaternary structure of the HIV-1 envelope oligomer. Virology 218:134–140 [CrossRef]
     [Google Scholar]
  59. Shi Y., Albert J., Francis G., Holmes H., Fenyö E. M. 2002; A new cell line-based neutralization assay for primary HIV type 1 isolates. AIDS Res Hum Retroviruses 18:957–967 [CrossRef]
     [Google Scholar]
  60. Simon F., Matheron S., Tamalet C. 9 other authors 1993; Cellular and plasma viral load in patients infected with HIV-2. AIDS 7:1411–1417 [CrossRef]
     [Google Scholar]
  61. Tamalet C., Simon F., Dhiver C., Matheron S., de Micco P., Gastao J. A., Brun-Vezinet F. 1995; Autologous neutralizing antibodies and viral load in HIV-2-infected individuals. AIDS 9:90–91
     [Google Scholar]
  62. Tersmette M., de Goede R. E. Y., Al B. J. M., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. 1988; Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol 62:2026–2032
     [Google Scholar]
  63. Thomas E. R., Shotton C., Weiss R. A., Clapham P. R., McKnight á. 2003; CD4-dependent and CD4-independent HIV-2: consequences for neutralization. AIDS 17:291–300 [CrossRef]
     [Google Scholar]
  64. von Gegerfelt A., Albert J., Morfeldt-Månson L., Broliden K., Fenyö E. M. 1991; Isolate-specific neutralizing antibodies in patients with progressive HIV-1-related disease. Virology 185:162–168 [CrossRef]
     [Google Scholar]
  65. Wahlberg J., Albert J., Lundeberg J., von Gegerfelt A., Broliden K., Utter G., Fenyö E. M., Uhlen M. 1991; Analysis of the V3 loop in neutralization-resistant human immunodeficiency virus type 1 variants by direct solid-phase DNA sequencing. AIDS Res Hum Retroviruses 7:983–990 [CrossRef]
     [Google Scholar]
  66. Weber J., Fenyö E.-M., Beddows S., Kaleebu P., Björndal A. 1996; Neutralization serotypes of human immunodeficiency virus type 1 field isolates are not predicted by genetic subtype. The WHO network for HIV isolation and characterization. J Virol 70:7827–7832
     [Google Scholar]
  67. Wei X., Decker J. M., Wang S. 12 other authors 2003; Antibody neutralization and escape by HIV-1. Nature 422:307–312 [CrossRef]
     [Google Scholar]
  68. Weiss R. A., Clapham P. R., Weber J. N., Whitby D., Tedder R. S., O'Connor T., Chamaret S., Montagnier L. 1988; HIV-2 antisera cross-neutralize HIV-1. AIDS 2:95–100 [CrossRef]
     [Google Scholar]
  69. Zhang L., Huang Y., He T., Cao Y., Ho D. D. 1996; HIV-1 subtype and second-receptor use. Nature 383:768 [CrossRef]
     [Google Scholar]
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Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation
J. Gen. Virol. 86, 3385 (2005); https://doi.org/10.1099/vir.0.81259-0
/content/journal/jgv/10.1099/vir.0.81259-0
/content/journal/jgv/10.1099/vir.0.81259-0
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