Identification of a second site in HIV-1 gp41 mediating binding to cells

Abstract

Previous studies by us and others showed that HIV-1 gp41 by the immunosuppressive domain (amino acids 583–599) could bind to human T, B and monocytic cell. Here, we characterize a region (amino acids 641–685) of HIV-1 gp41 that may be another site for gp41 binding. Besides peptides of the gp41 immunosuppressive domain, peptides of a second region (amino acids 641–685) could also inhibit rsgp41 (amino acids 539–684) binding to human cell lines U937 (monocytic cell line) and Raji (B cell line). An epitope (amino acids 669–674, ELDKWA) within this region is recognized by human monoclonal antibody 2F5. 2F5 shows broad-spectrum neutralizing capacity against HIV-1 laboratory strains and primary isolates (J. Virol. 1994, 68: 4031–4034; AIDS Res. Hum. Retrovir. 1994, 10: 1651–1658). We demonstrated by flow cytometry that mAb 2F5 could block gp41-binding to human cell lines H9 (T cells),Raji and U937, but the control mAb 4E10 that recognizes another region of gp41 (amino acids 686–728) and can not inhibit HIV infection, did not block this binding. These results indicate that the region (amino acids 641–685) of HIV-1 gp41 is the second site by which gp41 interacts with human cells, and suggest that the neutralization of HIV-1 infection by mAb 2F5 may be based on the fact that it blocks interaction of gp41 on virions with the gp41 binding molecules on human cells.