Role of HLA class I in HIV type 1-induced syncytium formation.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Role of HLA class I in HIV type 1-induced syncytium formation.

AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):1031-40. Unique Identifier : AIDSLINE MED/96424758
de Santis C; Robbioni P; Longhi R; Carrow E; Siccardi AG; Beretta A; DIBIT, S. Raffaele Scientific Institute, Milan, Italy.

Abstract: Neutralization of HIV-1 in vitro by anti-HLA class I antibodies suggests that class I molecules are involved in HIV-1 infection. HIV-infected cells can fuse with uninfected cells in a process that leads to the formation of multinucleated syncytia, involving an interaction between host and viral antigens expressed at the cell surfaces. We used a syncytium assay between the 8E5 cell line chronically infected with a pol-defective variant of LAV IIIb, and the CD4-positive cell line MOLT3, to study the role of HLA class I in HIV-1-induced cell fusion. By probing cells with a panel of anti-HLA monoclonal antibodies (MABs) we demonstrated that the fusion process is modulated specifically by C alleles of HLA class I expressed on uninfected cells but not by that on already infected cells. Addition of beta 2-microglobulin to the cocultures resulted in a dose-dependent enhancement in both the number and size of syncytia, whereas exogenous HLA-C-restricted peptides inhibited syncytium formation, implying that only certain conformational states of HLA class I are permissive for syncytium formation. Treatment of cocultures with HLA-Cw4-restricted peptides containing amino acid substitutions in the anchor residues showed that syncytium inhibition was dependent on conventional binding of the peptide inside the groove. The data indicate that HLA class I, in a conformation free of peptide but associated with beta 2-microglobulin, can directly influence virus-induced cell fusion.

Keywords: beta 2-Microglobulin/METABOLISM Antibodies, Monoclonal/IMMUNOLOGY Cell Line CD4-Positive T-Lymphocytes/IMMUNOLOGY/METABOLISM Giant Cells/*VIROLOGY Histocompatibility Antigens Class I/*IMMUNOLOGY Human HIV-1/*IMMUNOLOGY HLA-C Antigens/IMMUNOLOGY In Vitro Membrane Fusion/IMMUNOLOGY Models, Chemical Protein Conformation Support, Non-U.S. Gov't JOURNAL ARTICLE
970330
M9731494

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