1887

Abstract

Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus–cell interactions, IgG to CD4–gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4–gp120 complex) were extremely significant predictors of HIV exposure (<0·0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80585-0
2005-02-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/2/vir860339.html?itemId=/content/journal/jgv/10.1099/vir.0.80585-0&mimeType=html&fmt=ahah

References

  1. Bentwich Z., Kalinkovich A., Weisman Z. 1995; Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol Today 16:187–191 [CrossRef]
    [Google Scholar]
  2. Beretta A., Weiss S. H., Rappocciolo G. 10 other authors 1996; Human immunodeficiency virus type 1 (HIV-1)-seronegative injection drug users at risk for HIV exposure have antibodies to HLA class I antigens and T cells specific for HIV envelope. J Infect Dis 173:472–476 [CrossRef]
    [Google Scholar]
  3. Beyrer C., Artenstein A. W., Rugpao S. 9 other authors 1999; Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand. Chiang Mai HEPS Working Group. J Infect Dis 179:59–67 [CrossRef]
    [Google Scholar]
  4. Biasin M., Caputo S. L., Speciale L. 11 other authors 2000; Mucosal and systemic immune activation is present in human immunodeficiency virus-exposed seronegative women. J Infect Dis 182:1365–1374 [CrossRef]
    [Google Scholar]
  5. Burastero S. E., Casali P., Wilder R. L., Notkins A. L. 1988; Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 168:1979–1992 [CrossRef]
    [Google Scholar]
  6. Burastero S., Gaffi D., Lopalco L. 10 other authors 1996; Autoantibodies to CD4 in HIV type 1-exposed seronegative individuals. AIDS Res Hum Retrovir 12:273–280 [CrossRef]
    [Google Scholar]
  7. Casali P., Burastero S. E., Nakamura M., Inghirami G., Notkins A. L. 1987; Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science 236:77–81 [CrossRef]
    [Google Scholar]
  8. Clerici M., Barassi C., Devito C. 7 other authors 2002; Serum IgA of HIV-exposed uninfected individuals inhibit HIV through recognition of a region within the α-helix of gp41. AIDS 16:1731–1741 [CrossRef]
    [Google Scholar]
  9. Devito C., Broliden K., Kaul R. 10 other authors 2000a; Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells. J Immunol 165:5170–5176 [CrossRef]
    [Google Scholar]
  10. Devito C., Hinkula J., Kaul R., Lopalco L., Bwayo J. J., Plummer F., Clerici M., Broliden K. 2000b; Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate. AIDS 14:1917–1920 [CrossRef]
    [Google Scholar]
  11. Ditzel H. J., Rosenkilde M. M., Garred P., Wang M., Koefoed K., Pedersen C., Burton D. R., Schwartz T. W. 1998; The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: identification of chemokine and HIV-1-blocking human antibodies. Proc Natl Acad Sci U S A 95:5241–5245 [CrossRef]
    [Google Scholar]
  12. Dorrell L., Hessell A. J., Wang M., Whittle H., Sabally S., Rowland-Jones S., Burton D. R., Parren P. W. H. I. 2000; Absence of specific mucosal antibody responses in HIV-exposed uninfected sex workers from the Gambia. AIDS 14:1117–1122 [CrossRef]
    [Google Scholar]
  13. Furci L., Beretta A., Siccardi A., Lazzarin A., Confetti C., Magnani Z., Scarpellini P., Lopalco L., Burastero S. E. 1997a; Human immunodeficiency virus type 1 glycoprotein 120-specific T lymphocytes provide intermolecular help for anti-CD4 autoantibody production in exposed uninfected subjects. AIDS Res Hum Retrovir 13:1461–1469 [CrossRef]
    [Google Scholar]
  14. Furci L., Scarlatti G., Burastero S. & 13 other authors (1997b). Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4+ T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele. J Exp Med 186:455–460 [CrossRef]
    [Google Scholar]
  15. Kaul R., Trabattoni D., Bwayo J. J. 9 other authors 1999; HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers. AIDS 13:23–29 [CrossRef]
    [Google Scholar]
  16. Kaul R., Dong T., Plummer F. A. 12 other authors 2001; CD8+ lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J Clin Invest 107:1303–1310 [CrossRef]
    [Google Scholar]
  17. Lawn S. D., Butera S. T., Folks T. M. 2001; Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev 14:753–777 [CrossRef]
    [Google Scholar]
  18. Lehner T., Bergmeier L. A., Panagiotidi C. 9 other authors 1992; Induction of mucosal and systemic immunity to a recombinant simian immunodeficiency viral protein. Science 258:1365–1369 [CrossRef]
    [Google Scholar]
  19. Lehner T., Wang Y., Doyle C., Tao L., Bergmeier L. A., Mitchell E., Bogers W. M. J. M., Heeney J., Kelly C. G. 1999; Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques. Eur J Immunol 29:2427–2435 [CrossRef]
    [Google Scholar]
  20. Levy J. A., Scott I., Mackewicz C. 2003; Protection from HIV/AIDS: the importance of innate immunity. Clin Immunol 108:167–174 [CrossRef]
    [Google Scholar]
  21. Liu R., Paxton W. A., Choe S. 7 other authors 1996; Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367–377 [CrossRef]
    [Google Scholar]
  22. Lo Caputo S., Trabattoni D., Vichi F., Piconi S., Lopalco L., Villa M. L., Mazzotta F., Clerici M. 2003; Mucosal and systemic HIV-1-specific immunity in HIV-1-exposed but uninfected heterosexual men. AIDS 17:531–539 [CrossRef]
    [Google Scholar]
  23. Lopalco L., Magnani Z., Confetti C. 8 other authors 1999; Anti-CD4 antibodies in exposed seronegative adults and in newborns of HIV type 1-seropositive mothers: a follow-up study. AIDS Res Hum Retrovir 15:1079–1085 [CrossRef]
    [Google Scholar]
  24. Lopalco L., Barassi C., Pastori C. 7 other authors 2000a; CCR5-reactive antibodies in seronegative partners of HIV-seropositive individuals down-modulate surface CCR5 in vivo and neutralize the infectivity of R5 strains of HIV-1 in vitro. J Immunol 164:3426–3433 [CrossRef]
    [Google Scholar]
  25. Lopalco L., Pastori C., Cosma A., Burastero S. E., Capiluppi B., Boeri E., Beretta A., Lazzarin A., Siccardi A. G. 2000b; Anti-cell antibodies in exposed seronegative individuals with HIV type 1-neutralizing activity. AIDS Res Hum Retrovir 16:109–115 [CrossRef]
    [Google Scholar]
  26. Makedonas G., Bruneau J., Lin H., Sekaly R.-P., Lamothe F., Bernard N. F. 2002; HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity. AIDS 16:1595–1602 [CrossRef]
    [Google Scholar]
  27. Mazzoli S., Trabattoni D., Lo Caputo S. 13 other authors 1997; HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals. Nat Med 3:1250–1257 [CrossRef]
    [Google Scholar]
  28. Nakamura M., Burastero S. E., Notkins A. L., Casal P. 1988; Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1)+ B cells are polyreactive. J Immunol 140:4180–4186
    [Google Scholar]
  29. Nguyen M., Nouhin J., Ly N., Ing R., Phoung V., Barré-Sinoussi F., Reynes J.-M., Pancinco G. 2003; In vitro susceptibility to HIV-1 infection of peripheral blood mononuclear cells of seronegative partners of HIV-1-infected individuals in Cambodia. In Abstracts of the Second IAS Conference on HIV Pathogenesis and Treatment 13–16 July 2003; Paris
    [Google Scholar]
  30. Pashov A., Kenderov A., Kyurkchiev S. 7 other authors 2002; Autoantibodies to heat shock protein 90 in the human natural antibody repertoire. Int Immunol 14:453–461 [CrossRef]
    [Google Scholar]
  31. Potter M., Jones G., Dubois W., Williams K., Mushinski E. 2000; Myeloma proteins that bind Hsp65 (GroEL) are polyreactive and are found in high incidence in pristine induced plasmacytomas. Curr Top Microbiol Immunol 252:265–271
    [Google Scholar]
  32. Rizzardini G., Piconi S., Ruzzante S. 8 other authors 1996; Immunological activation markers in the serum of African and European HIV-seropositive and seronegative individuals. AIDS 10:1535–1542 [CrossRef]
    [Google Scholar]
  33. Rizzardini G., Trabattoni D., Saresella M., Piconi S., Lukwiya M., Declich S., Fabiani M., Ferrante P., Clerici M. 1998; Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program. AIDS 12:2387–2396 [CrossRef]
    [Google Scholar]
  34. Rowland-Jones S. L., McMichael A. 1995; Immune responses in HIV-exposed seronegatives: have they repelled the virus?. Curr Opin Immunol 7:448–455 [CrossRef]
    [Google Scholar]
  35. Rugeles M. T., Solano F., Díaz F. J., Bedoya V. I., Patiño P. J. 2002; Molecular characterization of the CCR 5 gene in seronegative individuals exposed to human immunodeficiency virus (HIV). J Clin Virol 23:161–169 [CrossRef]
    [Google Scholar]
  36. Salemi S., Caporossi A. P., Boffa L., Longobardi M. G., Barnaba V. 1995; HIVgp120 activates autoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing. J Exp Med 181:2253–2257 [CrossRef]
    [Google Scholar]
  37. Shacklett B. L., Means R. E., Larsson M. 8 other authors 2002; Dendritic cell amplification of HIV type 1-specific CD8+ T cell responses in exposed, seronegative heterosexual women. AIDS Res Hum Retrovir 18:805–815 [CrossRef]
    [Google Scholar]
  38. Shearer G. M., Clerici M. 1996; Protective immunity against HIV infection: has nature done the experiment for us?. Immunol Today 17:21–24 [CrossRef]
    [Google Scholar]
  39. Truong L. X., Luong T. T., Scott-Algara D. 11 other authors 2003; CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam. AIDS 17:1425–1434 [CrossRef]
    [Google Scholar]
  40. Yazdanbakhsh M., Kremsner P. G., van Ree R. 2002; Allergy, parasites, and the hygiene hypothesis. Science 296:490–494 [CrossRef]
    [Google Scholar]
  41. Zhu T., Corey L., Hwangbo Y., Lee J. M., Learn G. H., Mullins J. I., McElrath M. J. 2003; Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals. J Virol 77:6108–6116 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80585-0
Loading
/content/journal/jgv/10.1099/vir.0.80585-0
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