1887

Abstract

The hypothesis that open conformers of HLA-C on target cells might directly exert an effect on their infectability by human immunodeficiency virus (HIV) has been suggested previously. This was tested by exploiting the peculiar specificity of monoclonal antibody (mAb) L31 for HLA-C open conformers to show that normal levels of Env-driven fusion were restored in HLA-C transfectants of a major histocompatibility complex-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is now confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs) from 11 healthy donors. Infectability by HIV (strains IIIB and Bal and primary isolates) was significantly reduced (=0.016) in silenced cells compared with cells that maintained HLA-C expression in 10 of the

11 PBL donors. Normal infectability was resumed, together with HLA-C expression, when the effect of siRNA interference waned after several days in culture. Additional confirmation of the HLA-C effect was obtained in several assays employing HLA-C-positive and -negative cell lines, a number of HIV strains and also pseudoviruses. In particular, viruses pseudotyped with genes from HIV strains AC10 and QH0692.42 were assayed on siRNA-silenced lymphocytes from three healthy donors: the differences in infection with pseudoviruses were even higher than those observed in infections with normal viruses.

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2010-01-01
2019-11-15
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References

  1. Arosa, F. A., Santos, S. G. & Powis, S. J. ( 2007; ). Open conformers: the hidden face of MHC-I molecules. Trends Immunol 28, 115–123.[CrossRef]
    [Google Scholar]
  2. Benoit, L. A., Shannon, J., Chamberlain, J. W. & Miller, R. G. ( 2005; ). Influence of xenogeneic β 2-microglobulin on functional recognition of H-2Kb by the NK cell inhibitory receptor Ly49C. J Immunol 175, 3542–3553.[CrossRef]
    [Google Scholar]
  3. 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.[CrossRef]
    [Google Scholar]
  4. Cohen, G. B., Gandhi, R. T., Davis, D. M., Mandelboim, O., Chen, B. K., Strominger, J. L. & Baltimore, D. ( 1999; ). The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10, 661–671.[CrossRef]
    [Google Scholar]
  5. Connor, R. I., Chen, B. K., Choe, S. & Landau, N. R. ( 1995; ). Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206, 935–944.[CrossRef]
    [Google Scholar]
  6. Cosma, A., Blanc, D., Braun, J., Quillent, C., Barassi, C., Moog, C., Klasen, S., Spire, B., Scarlatti, G. & other authors ( 1999; ). Enhanced HIV infectivity and changes in gp120 conformation associated with viral incorporation of human leucocyte antigen class I molecules. AIDS 13, 2033–2042.[CrossRef]
    [Google Scholar]
  7. De Santis, C., Robbioni, P., Longhi, R., Carrow, E., Siccardi, A. G. & Beretta, A. ( 1996; ). Role of HLA class I in HIV type 1-induced syncytium formation. AIDS Res Hum Retroviruses 12, 1031–1040.[CrossRef]
    [Google Scholar]
  8. Eckert, D. M. & Kim, P. S. ( 2001; ). Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proc Natl Acad Sci U S A 98, 11187–11192.[CrossRef]
    [Google Scholar]
  9. Fellay, J., Shianna, K. V., Ge, D., Colombo, S., Ledergerber, B., Weale, M., Zhang, K., Gumbs, C., Castagna, A. & other authors ( 2007; ). A whole-genome association study of major determinants for host control of HIV-1. Science 317, 944–947.[CrossRef]
    [Google Scholar]
  10. Gonen-Gross, T., Achdout, H., Arnon, T. I., Gazit, R., Stern, N., Horejsi, V., Goldman-Wohl, D., Yagel, S. & Mandelboim, O. ( 2005; ). The CD85J/leukocyte inhibitory receptor-1 distinguishes between conformed and β 2-microglobulin-free HLA-G molecules. J Immunol 175, 4866–4874.[CrossRef]
    [Google Scholar]
  11. Grassi, F., Meneveri, R., Gullberg, M., Lopalco, L., Rossi, G. B., Lanza, P., De Santis, C., Brattsand, G., Butto, S. & other authors ( 1991; ). Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. J Exp Med 174, 53–62.[CrossRef]
    [Google Scholar]
  12. He, J., Choe, S., Walker, R., Di Marzio, P., Morgan, D. O. & Landau, N. R. ( 1995; ). Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 69, 6705–6711.
    [Google Scholar]
  13. Joliot, V., Goujon, C., Dumonceaux, J., Renard, A., Briand, P. & Hazan, U. ( 2001; ). A human immunodeficiency virus Env inducible transcription system to examine consequences of gp120 expression. J Virol Methods 98, 145–151.[CrossRef]
    [Google Scholar]
  14. Kirchherr, J. L., Lu, X., Kasongo, W., Chalwe, V., Mwananyanda, L., Musonda, R. M., Xia, S. M., Scearce, R. M., Liao, H. X. & other authors ( 2007; ). High throughput functional analysis of HIV-1 env genes without cloning. J Virol Methods 143, 104–111.[CrossRef]
    [Google Scholar]
  15. Li, M., Gao, F., Mascola, J. R., Stamatatos, L., Polonis, V. R., Koutsoukos, M., Voss, G., Goepfert, P., Gilbert, P. & other authors ( 2005; ). Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 79, 10108–10125.[CrossRef]
    [Google Scholar]
  16. Limou, S., Le Clerc, S., Coulonges, C., Carpentier, W., Dina, C., Delaneau, O., Labib, T., Taing, L., Sladek, R. & other authors ( 2009; ). Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 199, 419–426.[CrossRef]
    [Google Scholar]
  17. Mascola, J. R., Louder, M. K., Winter, C., Prabhakara, R., De Rosa, S. C., Douek, D. C., Hill, B. J., Gabuzda, D. & Roederer, M. ( 2002; ). Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells. J Virol 76, 4810–4821.[CrossRef]
    [Google Scholar]
  18. Matucci, A., Rossolillo, P., Baroni, M., Siccardi, A. G., Beretta, A. & Zipeto, D. ( 2008; ). HLA-C increases HIV-1 infectivity and is associated with gp120. Retrovirology 5, 68 [CrossRef]
    [Google Scholar]
  19. Mitra, A. K., Celia, H., Ren, G., Luz, J. G., Wilson, I. A. & Teyton, L. ( 2004; ). Supine orientation of a murine MHC class I molecule on the membrane bilayer. Curr Biol 14, 718–724.[CrossRef]
    [Google Scholar]
  20. Natali, P. G., Nicotra, M. R., Bigotti, A., Venturo, I., Marcenaro, L., Giacomini, P. & Russo, C. ( 1989; ). Selective changes in expression of HLA class I polymorphic determinants in human solid tumors. Proc Natl Acad Sci U S A 86, 6719–6723.[CrossRef]
    [Google Scholar]
  21. Rousseau, C. M., Birditt, B. A., McKay, A. R., Stoddard, J. N., Lee, T. C., McLaughlin, S., Moore, S. W., Shindo, N., Learn, G. H. & other authors ( 2006; ). Large-scale amplification, cloning and sequencing of near full-length HIV-1 subtype C genomes. J Virol Methods 136, 118–125.[CrossRef]
    [Google Scholar]
  22. Rusconi, S., Scozzafava, A., Mastrolorenzo, A. & Supuran, C. T. ( 2007; ). An update in the development of HIV entry inhibitors. Curr Top Med Chem 7, 1273–1289.[CrossRef]
    [Google Scholar]
  23. Schwartz, O., Alizon, M., Heard, J. M. & Danos, O. ( 1994; ). Impairment of T cell receptor-dependent stimulation in CD4+ lymphocytes after contact with membrane-bound HIV-1 envelope glycoprotein. Virology 198, 360–365.[CrossRef]
    [Google Scholar]
  24. Setini, A., Beretta, A., De Santis, C., Meneveri, R., Martayan, A., Mazzilli, M. C., Appella, E., Siccardi, A. G., Natali, P. G. & Giacomini, P. ( 1996; ). Distinctive features of the α1-domain α helix of HLA-C heavy chains free of β 2-microglobulin. Hum Immunol 46, 69–81.[CrossRef]
    [Google Scholar]
  25. Shimizu, Y., Geraghty, D. E., Koller, B. H., Orr, H. T. & DeMars, R. ( 1988; ). Transfer and expression of three cloned human non-HLA-A, B, C class I major histocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci U S A 85, 227–231.[CrossRef]
    [Google Scholar]
  26. van Manen, D., Kootstra, N. A., Boeser-Nunnink, B., Handulle, M. A., van't Wout, A. B. & Schuitemaker, H. ( 2009; ). Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection. AIDS 23, 19–28.[CrossRef]
    [Google Scholar]
  27. Wei, X., Decker, J. M., Liu, H., Zhang, Z., Arani, R. B., Kilby, J. M., Saag, M. S., Wu, X., Shaw, G. M. & Kappes, J. C. ( 2002; ). Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46, 1896–1905.[CrossRef]
    [Google Scholar]
  28. White, J., Matlin, K. & Helenius, A. ( 1981; ). Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses. J Cell Biol 89, 674–679.[CrossRef]
    [Google Scholar]
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