U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been described. We evaluated the role of host factors in their differential ability to support HIV-1 replication. Plus clones constitutively produced TNF-alpha and viral replication was inhibited by neutralization of endogenous TNF-alpha. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-alpha, which also further accelerated the kinetics of infection in plus clones. We observed an increased accumulation of proviral DNA within one round of HIV-1 replication following TNF-a treatment of plus cells. This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identify 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 transcription and also enhance HIV-1 replication by increasing the surface density of CXCR
