Interferon gamma stimulates cell-mediated transmission of HIV type 1 from abortively infected endothelial cells.

Human umbilical vein endothelial cells (HUVEC) can be abortively infected with HIV-1, but virus production is rescued by T cells. The influence of interferon gamma (IFN-gamma) in this experimental system has been investigated. HUVEC either untreated or treated with IFN-gamma were infected with HIV-1 and cocultivated with rescuer T cells. Virus yield was subsequently assessed as antigen or infectivity present in the cocultures supernatants. Viral DNA in HUVEC was detected by polymerase chain reaction. Transmission electron microscopy was used to establish direct interactions between HUVEC and T cells. Intercellular adhesion molecule (ICAM)-1 expression by HUVEC was measured by enzyme-linked immunoassay. Monoclonal antibodies (MAbs) to adhesion molecules were used to block the rescue of infection by T cells. Treatment of HUVEC with IFN-gamma caused a dose-dependent enhancement of HIV-1 yield in cocultures of HUVEC with either lymphoblastoid or normal T cells. IFN-gamma was effective also when administered to HUVEC 1 day after infection. Neither HIV-1 adsorption nor virus reverse transcription was stimulated by IFN. Physical contact between HIV-1-infected HUVEC and rescuer T cells was observed, and discrete tracts of discontinuity between the juxtaposed membranes were detected, being more frequent when HUVEC had been treated with IFN-gamma. Treatment with IFN determined an increase of ICAM-1 expression by HUVEC, and anti ICAM-1 MAbs inhibited HIV-1 rescue, being more effective when HUVEC had been exposed to IFN-gamma. Treatment of T cells with anti-LFA-1 Mab also inhibited HIV-1 rescue. The enhancing effect of IFN-gamma could be the result of stimulated transfer of HIV-1 infection from HUVEC to T cells, possibly mediated by enhanced expression of ICAM-1 by HUVEC, that could, in turn, enhance the efficiency of membrane interaction with T cells. Since in HIV-1-infected patients circulating IFN-gamma is enhanced, our results can have pathogenetic implications.