Soluble receptor-induced retroviral infection of receptor-deficient cells

Current models of retroviral entry hypothesize that interactions between th e host cell receptor(s) and viral envelope protein induce structural change s in the envelope protein that convert it to an active conformation, allowi ng it to mediate fusion with the membrane. Recent evidence supporting this hypothesis is the demonstration that Tva, the receptor for subgroup A avian sarcoma and leukosis virus (ASLV-A), induces conformational changes in the viral envelope protein. These changes include conversion of the envelope p rotein to an active, membrane-binding state likely representing a fusogenic conformation. To determine whether binding of the soluble Tva (sTva) recep tor was sufficient to activate fully the fusogenic potential of the ASLV-A envelope protein, we have evaluated the ability of ASLV-A to infect recepto r-deficient cell Lines in the presence of sTva. Soluble receptor efficientl y mediated infection of cells devoid of endogenous Tva in a dose-dependent manner, and this infection was dependent absolutely on the addition of sTva . The infectivity of the virus was enhanced dramatically in the presence of the polycationic polymer Polybrene or when centrifugal forces were applied during inoculation, resulting in viral titers comparable to those achieved on cells expressing endogenous receptor. sTva functioned to mediate infect ion at low concentrations, approaching the estimated binding constant of th e receptor and viral envelope protein. These results demonstrate that recep tor binding can activate the ASLV-A envelope protein and convert it to a fu sogenic conformation competent to mediate the fusion of the viral and cellu lar membranes.