Tumor necrosis factor-alpha drives HIV-1 replication in U937 cell clones and upregulates CXCR4

U937 cell clones in which efficient (plus) vs poor (minus) replication of H IV-1 occurs have been described. We evaluated the role of host factors in t heir differential ability to support HIV-1 replication. Plus clones constit utively produced TNF-alpha and viral replication was inhibited by neutraliz ation of endogenous TNF-alpha, However, HIV-I replication was strongly upre gulated in minus clones by exogenous TNF-alpha, which also further accelera ted the kinetics of infection in plus clones, We observed an increased accu mulation of proviral DNA within one round of HIV-I replication following TN F-alpha treatment of plus cells, This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identif y TNF-alpha as one correlate that contributes to the higher ability of U937 -plus clones to sustain HIV-1 replication, Furthermore, we suggest that TNF -alpha may affect steps of the viral life cycle that occur earlier than tra nscription and also enhance HIV-I replication by increasing the surface den sity of CXCR4. (C) 2001 Academic Press.