In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression (original) (raw)

Nature Medicine volume 3, pages 1259–1265 (1997)Cite this article

Abstract

Following the identification of the C-C chemokines RANTES, MIP-1α and MIP-1β as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells1, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses2–8. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1α and MIP-1β receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains3–7,9,10 and by simian immunodeficiency virus (SIV)11, whereas CXCR4, a receptor for the C-X-C chemokine SDF-1 (ref. 12, 13), is used by MT2-tropic HIV-1 and HIV-2, but not by SIV (ref. 2-7, 9-11, 14). Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates4,6,8. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice4,15. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1α and MIP-1β, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain of gp120 were associated with the loss of sensitivity to C-C chemokines and the shift in co-receptor usage. These results suggest an adaptive evolution of HIV-1 in vivo, leading to escape from the control of the antiviral C-C chemokines.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Cocchi, F. et al. Identification of RANTES, MIP-1α, MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270, 1811–1815 (1995).
    Article CAS PubMed Google Scholar
  2. Feng, Y., Broder, C.C., Kennedy, P.E. & Berger, E.A. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877 (1996).
    Article CAS PubMed Google Scholar
  3. Alkhatib, G. et al. CC CRK5: A RANTES, MIP-1 α, MIP-1 β receptor as a fusion Co-factor for macrophage-tropic HIV-1. Science 272, 1955–1958 (1996).
    Article CAS PubMed Google Scholar
  4. Choe, H. et al. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85, 1135–1148 (1996).
    Article CAS PubMed Google Scholar
  5. Deng, H. et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661–666 (1996).
    Article CAS PubMed Google Scholar
  6. Doranz, B.J. et al. A dual-tropic primary HIV-1 isolate that uses fusin and the β-chemokine receptors CKR-5, CKR-3, and CRK-2b as fusin cofactors. Cell 85, 1149–1158 (1996).
    Article CAS PubMed Google Scholar
  7. Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CRK-5. Nature 381, 667–673 (1996).
    Article CAS PubMed Google Scholar
  8. Liao, F. et al. STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med. 185, 2015–2023 (1997).
    Article CAS PubMed PubMed Central Google Scholar
  9. Connor, R.I., Sheridan, K.E., Ceradini, D., Choe, S. & Landau, N.R. Change in coreceptor use correlates with disease progression in HIV-1 infected individuals. J. Exp. Med. 185, 621–628 (1997).
    Article CAS PubMed PubMed Central Google Scholar
  10. Heredia, A., Vallejo, A., Soriano, V., Epstein, J.S. & Hewlett, I.K. Chemokine receptors and HIV-2. AIDS 11, 1198–1199 (1997).
    Article CAS PubMed Google Scholar
  11. Chen, Z., Zhou, P., Ho, D.D., Landau, N.R. & Marx, P.A. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J. Virol. 71, 2705–2714 (1997).
    CAS PubMed PubMed Central Google Scholar
  12. Bleul, C.C. et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382, 829–833 (1996).
    Article CAS PubMed Google Scholar
  13. Oberlin, E. et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382, 833–835 (1996).
    Article CAS PubMed Google Scholar
  14. Endres, M.J. et al. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87, 745–756 (1996).
    Article CAS PubMed Google Scholar
  15. Cocchi, F. et al. The V3 domain of HIV-1 envelope glycoprotein gp120 is critical for chemokine-mediated blockade of infection. Nature Med. 2, 1244–1247 (1996).
    Article CAS PubMed Google Scholar
  16. Valentin, A., Albert, J., Fenyö, E.M. & Åsjö B. Dual tropism for macrophages and lymphocytes is a common feature of primary HIV-1 and HIV-2 isolates. J. Virol 68, 6684–6689 (1994).
    CAS PubMed PubMed Central Google Scholar
  17. Schmidtmayerova, H., Sherry, B. & Bukrinsky, M. Chemokines and HIV replication. Nature 382, 767 (1996).
    Article CAS PubMed Google Scholar
  18. Moriuchi, M., Moriuchi, H., Combadiere, C., Murphy, P.M. & Fauci, A.S. CD8+ T-cell-derived factor(s), but not β-chemokines RANTES, MIP-1α, and MIP-1β, suppress HIV-1 replication in monocyte/macrophages. Proc. Natl. Acad. Sci. USA 93, 15341–15345 (1996).
    Article CAS PubMed PubMed Central Google Scholar
  19. Verani, A. et al. C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells. J. Exp. Med. 185, 805–816 (1997).
    Article CAS PubMed PubMed Central Google Scholar
  20. de Jong, J.-J., de Ronde, A., Keulen, W., Tersmette, M. & Goudsmit, J. 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 (1992).
    CAS PubMed PubMed Central Google Scholar
  21. Fouchier, R.A.M. et al. Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J. Virol. 66, 3183–3187 (1992).
    CAS PubMed PubMed Central Google Scholar
  22. Wu, L., et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR5. Nature 384, 179–183 (1996).
    Article CAS PubMed Google Scholar
  23. Trkola, A., et al. CD4-dependent, antibody-sensitive interaction between HIV-1 and its co-receptor CCR5. Nature 384, 184–187 (1996).
    Article CAS PubMed Google Scholar
  24. Åsjö, B., et al. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet ii, 660–662 (1986).
    Google Scholar
  25. Koot, M. et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann. Intern. Med. 118, 681–688 (1993).
    Article CAS PubMed Google Scholar
  26. Scarlatti, G. et al. Polymerase chain reaction, virus isolation and antigen assay in HIV-1 antibody positive mothers and their children. AIDS 5, 1173–1178 (1991).
    Article CAS PubMed Google Scholar
  27. Centers for Disease Control and Prevention. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Morbid. Mortal. Wkly. Rep. 43, 1–10 (1994).
  28. Martin, N. et al. Workshop on perinatally acquired human immunodeficiency virus infection in long-term surviving children: A collaborative study of factors contributing to slow disease progression. AIDS Res. Hum. Retroviruses 12, 1565–1570 (1996).
    Article CAS PubMed Google Scholar
  29. Scarlatti, G. et al. Mother-to-child transmission of human immunodeficiency virus type 1: Correlation with neutralizing antibodies against primary isolates. J. Infect. Dis. 168, 207–210 (1993).
    Article CAS PubMed Google Scholar
  30. Harada, S., Koyanagi, Y. & Yamamoto, N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science 229, 563–566 (1985).
    Article CAS PubMed Google Scholar
  31. Rosen, C.A., Sodroski, J.G., Campbell, K. & Haseltine, W.A. Construction of recombinant murine retroviruses that express the human T-cell leukemia virus type II and human T-cell lymphotropic virus type III trans activator genes. J. Virol. 57, 379–384 (1986).
    CAS PubMed PubMed Central Google Scholar
  32. Clapham, P.R., Blanc, D. & Weiss, R.A. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by simian immunodeficiency virus. Virology 181, 703–715 (1991).
    Article CAS PubMed Google Scholar
  33. Scarlatti, G. et al. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc. Natl. Acad. Sci. USA 90, 1721–1725 (1993).
    Article CAS PubMed PubMed Central Google Scholar
  34. Myers, G., Korber, B., Berzofsky, J.A., Smith, R.F. & Pavlakis, G.N. in: Human retro-viruses and AIDS: A compilation and analysis of nucleic acids and amino acid sequences. (Los Alamos Natl. Laboratories, Los Alamos, NM, 1995).
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Unit of Immunobiology of HIV, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
    Gabriella Scarlatti, Eleonora Tresoldi, Claudia Colognesi & Antonio G. Siccardi
  2. Unit of Human Virology, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
    Mauro S. Malnati & Paolo Lusso
  3. Microbiology and Tumor Biology Center, Karolinska Institute, Doktorsringen 13, 17177, Stockholm, Sweden
    Åsa Björndal, Robert Fredriksson & Eva Maria Fenyö
  4. Howard Hughes Medical Institute, Skirball Institute for BioMolecular Medicine, New York University, 540 First Avenue, New York, New York, 10016, USA
    Hong Kui Deng & Dan R. Littman
  5. First Clinic of Pediatrics, University of Milan, Via Commenda 9, 20128, Milan, Italy
    Anna Plebani

Authors

  1. Gabriella Scarlatti
    You can also search for this author inPubMed Google Scholar
  2. Eleonora Tresoldi
    You can also search for this author inPubMed Google Scholar
  3. Åsa Björndal
    You can also search for this author inPubMed Google Scholar
  4. Robert Fredriksson
    You can also search for this author inPubMed Google Scholar
  5. Claudia Colognesi
    You can also search for this author inPubMed Google Scholar
  6. Hong Kui Deng
    You can also search for this author inPubMed Google Scholar
  7. Mauro S. Malnati
    You can also search for this author inPubMed Google Scholar
  8. Anna Plebani
    You can also search for this author inPubMed Google Scholar
  9. Antonio G. Siccardi
    You can also search for this author inPubMed Google Scholar
  10. Dan R. Littman
    You can also search for this author inPubMed Google Scholar
  11. Eva Maria Fenyö
    You can also search for this author inPubMed Google Scholar
  12. Paolo Lusso
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Scarlatti, G., Tresoldi, E., Björndal, Å. et al. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.Nat Med 3, 1259–1265 (1997). https://doi.org/10.1038/nm1197-1259

Download citation