Are Viruses Inhibited by APOBEC3 Molecules from Their Host Species 英文参考文献.docVIP

Opinion AreVirusesInhibitedbyAPOBEC3MoleculesfromTheir HostSpecies? SusanR.Ross* DepartmentofMicrobiologyandAbramsonFamilyCancerCenter,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Organismsadapttoinfectiousagentsby developing protective responses, and con- versely,infectiousagentsdevelopadaptive countermeasures to these responses. Host defenses against infectious agents include adaptive and innate immune responses (e.g., natural killer cells, Toll-like recep- tors,andinterferons).Recently,additional host defense systems against viruses have been identified. These include the TRIM [1],RIGI/MDA5[2],Bst2/tetherin[3,4], andAPOBEC3(A3)[5]proteins.Manyof these anti-viral defense mechanisms were identified through the discovery of viral geneproductsthatcounteracttheiraction, and thus it has been proposed that only virusesresistanttohost-encodedrestriction factors persist. However, recent in vivo work in the murine system has indicated that endogenous A3 proteins play impor- tant roles in limiting pathogenicity by murine viruses even though they only partially restrict infection [6–8]. Here I argue that these recent studies emphasize thecriticalimportanceofstudyingnatural pathogenic viruses and host restriction factorsinvivo. factor (Vif) [5]. hA3G and subsequently hA3FwereshowntoinhibitHIV-1lacking the vif gene. In vif-deficient HIV-1 pro- ducer cells, both hA3G and hA3F are packagedintoprogenyvirionsviainterac- tion with the nucleocapsid (NC) protein and viral RNA. Once packaged, hA3 proteinsinhibitinfectionintargetcellsby deaminatingdeoxycytidineresiduesonthe resistanttotheA3proteinsoftheirnatural hosts.Forexample,ithasbeenshownthat human T cell leukemia virus I (HTLVI), MasonPfizermonkeyvirus(MPMV),and MLV do not efficiently package human, monkey, or mouse A3 proteins, respec- tively, because of weak interactions be- tween the NC proteins and the host A3 [38–46], although other studies have DNA minus strand following reverse shownsomepa