LIGAND PASSING BY THE P75 TUMOR-NECROSIS-FACTOR RECEPTOR ENHANCES HIV-1 ACTIVATION

Recently, a HIV-dependent upmodulation of the p75 tumour necrosis fact or receptor (TNFr75) was observed using latently-infected OM-10.1 prom yelocytes; although the participation of TNFr75 in HIV-1 activation re mained undefined, Here, using receptor cross-linking by agonistic anti bodies, no direct HIV-1 activation via TNFr75 was observed, Signalling via the p55 tumour necrosis factor receptor (TNFr55) accounted for th e full extent of HIV-1 activation in OM-10.1 cultures. However, in tum our necrosis factor alpha (TNF-alpha) dose titration experiments, anti body blockade of TNFr75 decreased the dose response markedly, indicati ng a ligand passing function, TNFr75 blockade did not alter the dose r esponse to agonistic TNFr55 antibody induction; verifying that the eff ect on the TNF-alpha dose response was not due to negative signalling or cytolysis, These results demonstrate that, although not directly in volved in signal transduction resulting in HIV-1 activation, TNFr75 ca n serve a critical ligand passing function and permit continued HIV-1 expression during limited TNF-alpha availability. (C) 1996 Academic Pr ess Limited