HIV TYPE-1 GROWN ON INTERFERON GAMMA-TREATED U937 CELLS SHOWS SELECTIVE INCREASE IN VIRION-ASSOCIATED INTERCELLULAR-ADHESION MOLECULE-1 AND HLA-DR AND ENHANCED INFECTIVITY FOR CD4-NEGATIVE CELLS

Cellular adhesion molecules, such as ICAM-1, -2, and-3; LFA-1; and HLA class I and II are incorporated into HIV-1 virions during budding from infected cells, These virion-associated molecules can be involved in the adsorption to susceptible cells displaying the corresponding counterligands, A number of cytokines have been shown to upregulate the cellular expression of adhesion molecules, such as ICAM-1 and HLA-DR. In this study we investigated the effects of IFN-gamma on the incorporation of ICAM-1, LFA-1, and HLA-DR into mature HIV-1 progeny from chronically infected cells, The ability of such virus progeny to infect either CD4-positive or -negative cells was also investigated. The results indicate that IFN-gamma stimulates the expression of ICAM-1 and of HLA-DR on HIV-1-infected cells, whereas LFA-1 expression is unaffected, The same modifications were also observed on virus progeny, because specific MAbs to ICAM-1 and HLA-DR captured infectious HIV-1 from IFN-treated cells with higher efficiency as compared to virus from control cells, whereas virus binding to anti LFA-1 MAb was unchanged. Moreover, the HIV-1 progeny released from IFN-treated cells showed an increased ability to bind to and to infect CD4-negative cells, whereas the infectivity was basically unchanged for CD4-positive cells. Our results suggest that cytokines, as well as other soluble factors, may expand the host cell range of HIV-1, possibly through modifications of the cell-derived surface molecules on the virions, These could, in turn, act as alternative or additional ligands for virus attachment to host cells that display the corresponding counterreceptor(s).