Tumor necrosis factor enhances murine SL3-3 retrovirus replication

Synthesis of extracellular virions from NIH 3T3 cells productively infected with the murine leukemogenic SL3-3 retrovirus, was significantly increased by exposure to recombinant human tumor necrosis factor (rHuTNF). Compared to control cells SL3-3 virus production was 7-10-fold greater in cultures treated for 24 hours with 100-400 units of rHuTNF/cm2 of cell layer. In contrast, identical treatment of these cells with natural murine interferon alpha/beta, recombinant murine interferon-gamma, or recombinant human IL-2 consistently reduced SL3-3 virion production. Although both interferon (IFN) preparations decreased virion production by 25-95% within a 24 hour period, increased SL3-3 replication was observed following simultaneous addition of rHuTNF and either IFN. Increases in SL3-3 virus production did not require the constant presence of rHuTNF; elevated viral synthesis was detected 2 days after short pulse exposures of 30 minutes to 2 hours. Infected NIH 3T3 cells exposed to 200 units rHuTNF/cm2 of cell layer for 48 hours also continued to produce increased levels of SLS-3 virions 2 weeks after treatment.