Identification of CD7 glycoprotein as an accessory molecule in HIV-1-mediated syncytium formation and cellfree infection.
A major cytopathic effect seen upon in vitro infection of CD4+ human T cells by the HIV is cell-to-cell fusion that results in giant cell (or syncytium) formation. Membrane fusion is required for infection by cellfree virions and in syncytium formation. We report here that the human T cell surface molecule, CD7, is important for the HIV-1 fusion process. CD7 is a roughly 40-kDa glycoprotein member of the Ig supergene family that is expressed early in the ontogeny of thymocytes and on the majority of peripheral blood T cells, as well as on NK cells and a small subpopulation of B cells. Anti-CD7 mAbs inhibited HIV-1-induced cell-cell fusion and prevented cellfree infection of SupT1 cells. The antisyncytial activity of the CD7 Abs is not because of cross-reactivity with CD4 or with viral proteins. Epitope mapping revealed at least two regions of the molecule that are important for preventing membrane fusion. Cells rendered CD7- are poorly infectable by cellfree virus. Additionally, cells rendered CD7- are more easily inhibited from fusing in syncytium formation assays. The collective results support a central role for human CD7 in the process of HIV infection.
Sato
A I
AI
Department of Pathology, University of Pennsylvania, Philadelphia 19104.
Balamuth
F B
FB
Ugen
K E
KE
Williams
W V
WV
Weiner
D B
DB
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D015704:CD4 Antigens / Q000276:immunology; D002459:Cell Fusion; D002460:Cell Line; D003429:Cross Reactions; D003588:Cytopathogenic Effect, Viral; D000939:Epitopes; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D000939:Epitopes