AEGiS-07IAC: CD4 independent fusion and infection by HIV-2 strains: enhancement by soluble CD4.

7th International AIDS Conference


Florence, Italy — June 16-21, 1991

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CD4 independent fusion and infection by HIV-2 strains: enhancement by soluble CD4.

Int Conf AIDS 1991 Jun 16-21; 7:41 (abstract no. M.A.78)
Clapham P, McKnight A, Weiss R; Chester Beatty Laboratories, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK

OBJECTIVE: We have characterized HIV-2 fusion and infection of CD4-negative human cell lines.

METHODS: HIV-2 strains used were LAV-2ROD, SBL6669, CBL-20, CBL-21, CBL-22 and CBL-23. Human cells included RD/TE671 rhabdomyosarcoma, U87 glioma, HeLa carcinoma, Raji and Daudi B cell lines. HIV-2 fusion was tested by overnight cocultivation of producer cells with appropriate test cells. Cell-free HIV-2 infectivity was titrated by the TCID method. Recombinant baculovirus LAV-2ROD env gp110 was labelled with 125I using Enzymobeads (Bio-Rad).

RESULTS: A substrain of LAV-2ROD (LAV-2/B) efficiently induced fusion of several CD4- human cell lines. SBL6669 and CBL-22 also induced syncytia but less efficiently. RD/TE671 and Daudi cells were most sensitive to fusion, which was not blocked by soluble CD4 (sCD4) or by inhibitory CD4 monoclonal antibodies, but was specifically inhibited by HIV-2 human sera. sCD4 either induced or enhanced fusion by all HIV-2 strains tested. In cell-free infection by HIV-2, the 10(3) TCID50 of LAV-2/B on CD4- cells was only 10-fold less than that on the CD4+ T-cell line, C8166. CBL-20 was only infectious for CD4- cells after treatment with sCD4. HIV-2 envelope glycoprotein (gp110) bound to CD4- RD/TE671 cells. Binding was enhanced by sCD4, but inhibited by HIV-2+ sera. Again, binding of gp110 was 10-fold higher on CD4+ cells.

CONCLUSIONS: HIV-2 strains can fuse and infect CD4- human cell lines. This infection is probably mediated by gp110 binding to an unknown cell surface receptor, and the gp110 domain involved may become more accessible following sCD4 treatment. We do not as yet know whether the alternative receptor is also required for CD4-dependent entry.

Keywords: AEGIS, Antigens, CD4, HIV-2, Recombinant Proteins, Cell Line, T-Lymphocytes, Giant Cells, Antibodies, Monoclonal, SK&F 106528, Human, ICA7KWDaegis,antigens,cd4,hiv-2,recombinantproteins,cellline,t-lymphocytes,giantcells,antibodies,monoclonal,sk&f106528,human,ica7
910616
MA78

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