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Glyco-Gag in the virion also rendered MLV resistant to other cytosolic sensors of viral reverse transcription products in newly infected cells. Strikingly, glyco-Gag mutant virus reverted to glyco-Gag–containing virus only in WT and not APOBEC3 KO mice, indicating that counteracting APOBEC3 is the major function of glyco-Gag. Thus, in contrast to the HIV viral infectivity factor protein, which prevents APOBEC3 packaging in the virion, the MLV glyco-Gag protein uses a unique mechanism to counteract the antiviral action of APOBEC3 in vivo—namely, protecting the reverse transcription complex in viral cores from APOBEC3. These data suggest that capsid integrity may play a critical role in virus resistance to intrinsic cellular antiviral resistance factors that act at the early stages of infection.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2013,"id":47504,"datarank":2.404089565506638,"base_score":4.553876891600541,"endowment":4.553876891600541,"self_citation_contribution":0.6830815337400812,"citation_network_contribution":1.7210080317665566,"self_endowment_contribution":0.6830815337400812,"citer_contribution":1.7210080317665566,"corpus_percentile":null,"corpus_rank":null,"citation_count":94,"citer_count":65,"citers_with_citation_signal":54,"citers_with_endowment":54,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":219828,"name":"Takayuki Nitta","orcid":null,"position":1,"is_corresponding":false},{"id":219829,"name":"Swathi Kotla","orcid":null,"position":2,"is_corresponding":false},{"id":219830,"name":"Dat Ha","orcid":null,"position":3,"is_corresponding":false},{"id":219831,"name":"Kunio Nagashima","orcid":null,"position":4,"is_corresponding":false},{"id":219832,"name":"Alan R. 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Using virus isolated from infected WT and APOBEC3 KO mice, we demonstrate that the MLV glycosylated Gag protein (glyco-Gag) enhances viral core stability. Moreover, in vitro endogenous reverse transcription reactions of the glyco-Gag mutant virus were substantially inhibited compared with WT virus, but only in the presence of APOBEC3. Thus, glyco-Gag rendered the reverse transcription complex in the viral core resistant to APOBEC3. Glyco-Gag in the virion also rendered MLV resistant to other cytosolic sensors of viral reverse transcription products in newly infected cells. Strikingly, glyco-Gag mutant virus reverted to glyco-Gag–containing virus only in WT and not APOBEC3 KO mice, indicating that counteracting APOBEC3 is the major function of glyco-Gag. Thus, in contrast to the HIV viral infectivity factor protein, which prevents APOBEC3 packaging in the virion, the MLV glyco-Gag protein uses a unique mechanism to counteract the antiviral action of APOBEC3 in vivo—namely, protecting the reverse transcription complex in viral cores from APOBEC3. These data suggest that capsid integrity may play a critical role in virus resistance to intrinsic cellular antiviral resistance factors that act at the early stages of infection.</jats:p>","is_dataset_classified":null,"base_score":4.553876891600541,"endowment":4.553876891600541,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23671100","pmcid":"PMC3670389","openalex_id":"https://openalex.org/W2131302051","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32 CA115299","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32-AI07324","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"F32 AI100512","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA016520","title":null},{"funder_name":"PHS HHS","grant_id":"HHSN26120080001E","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01-AI-085015","title":null},{"funder_name":"NIAID NIH 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Research and Treatment","Cytomegalovirus and herpesvirus research","interferon and immune responses","Biology","Medicine","Animals","Blotting, Western","Cytidine Deaminase","DNA Primers","Gene Products, gag","Glycosylation","Host-Pathogen Interactions","Leukemia Virus, Murine","Mice","Mice, Inbred BALB C","Mice, Inbred C57BL","Mice, Knockout","NIH 3T3 Cells","Reverse Transcriptase Polymerase Chain Reaction","Reverse Transcription"],"mesh_terms":["Animals","Cytidine Deaminase","Glycosylation","Mice, Inbred BALB C","Mice, Inbred C57BL","Leukemia Virus, Murine","Blotting, Western","Gene Products, gag","DNA Primers","Mice, Knockout","Reverse Transcriptase Polymerase Chain Reaction","NIH 3T3 Cells","Reverse Transcription","Mice","Host-Pathogen Interactions"],"keywords":["Murine leukemia virus","Biology","Group-specific antigen","Gammaretrovirus","Virus","Capsid","Transcription (linguistics)","Infectivity","Reverse transcriptase","Myristoylation","Mutant","Virology","Endogenous 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