Soluble receptor-induced retroviral infection of receptor-deficient cells.
Current models of retroviral entry hypothesize that interactions between the host cell receptor(s) and viral envelope protein induce structural changes in the envelope protein that convert it to an active conformation, allowing 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 protein to an active, membrane-binding state likely representing a fusogenic conformation. To determine whether binding of the soluble Tva (sTva) receptor was sufficient to activate fully the fusogenic potential of the ASLV-A envelope protein, we have evaluated the ability of ASLV-A to infect receptor-deficient cell lines in the presence of sTva. Soluble receptor efficiently 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 infection at low concentrations, approaching the estimated binding constant of the receptor and viral envelope protein. These results demonstrate that receptor binding can activate the ASLV-A envelope protein and convert it to a fusogenic conformation competent to mediate the fusion of the viral and cellular membranes.
Damico
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Department of Microbiology, Graduate Program in Cellular and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
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D001355:Alpharetrovirus / Q000378:metabolism / Q000472:pathogenicity*; D030161:Avian Proteins; D002460:Cell Line; D015686:Gene Products, env / Q000378:metabolism*; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D011991:Receptors, Virus / Q000172:deficiency / Q000302:isolation & purification / Q000378:metabolism*; D012995:Solubility
D030161:Avian Proteins; D015686:Gene Products, env; D011991:Receptors, Virus; C088745:Tva receptor; D006583:Hexadimethrine Bromide