Retroviral infection in vivo requires an immune escape virulence factor encrypted in the envelope protein of oncoretroviruses.

摘要: We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins (Envs). The envelope-mediated immunosuppression was manifested by the ability of proteins, when expressed allogeneic tumor cells normally rejected engrafted mice, to allow these escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation specifically abolishes IS activity without affecting “mechanical” fusogenic function entire envelope. Here, genetically “switched off’ an infectious retrovirus, Friend leukemia virus, while preserving mutant infectivity both ex vivo in vivo, thus allowing us test functional importance retrovirus physiology. Remarkably, show, that non-IS virus displays same propagation kinetics as its WT counterpart irradiated immunocompromised mice but it is rapidly totally cleared from normal immunocompetent which become fully protected against challenge with retrovirus. cell depletion strategies, further establish enables escape innate (natural killer cells) adaptive (CD8 T antiviral effectors. Finally, show inactivated virions induce higher humoral cellular responses than their counterparts. In conclusion, our work demonstrates critical role Env-induced for identifies unique definite target antiretroviral therapies vaccine also characterized human T-cell (HTLV) xenotropic virus-related (XMRV) retroviruses, opening unprecedented prospects treatment diseases.