{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":54,"searchCount":0},"additional":{"submitter":["Halemano K"],"funding":["NIAID NIH HHS"],"pagination":["7759-64"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4040588"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["111(21)"],"pubmed_abstract":["Somatic hypermutation (SHM) is an integral process in the development of high-affinity antibodies that are important for recovery from viral infections and vaccine-induced protection. Ig SHM occurs predominantly in germinal centers (GC) via the enzymatic activity of activation-induced deaminase (AID). In contrast, the evolutionarily related apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 3 (APOBEC3) proteins are known to restrict retroviruses, including HIV-1. We previously reported that mouse APOBEC3 encodes Recovery from Friend virus 3 (Rfv3), a classical resistance gene in mice that promotes the neutralizing antibody response against retrovirus infection. We now show that APOBEC3/Rfv3 complements AID in driving Ig SHM during retrovirus infection. Analysis of antibody sequences from retrovirus-specific hybridomas and GC B cells from infected mice revealed Ig heavy-chain V genes with significantly increased C-to-T and G-to-A transitions in wild-type as compared with APOBEC3-defective mice. The context of the mutations was consistent with APOBEC3 but not AID mutational activity. These findings help explain the role of APOBEC3/Rfv3 in promoting the neutralizing antibody responses essential for recovery from retroviral infection and highlight APOBEC3-mediated deamination as a previously unidentified mechanism for antibody diversification in vivo."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection."],"pmcid":["PMC4040588"],"funding_grant_id":["P30 AI027763","R01 AI116603","R01 AI090795","R56 AI084123"],"pubmed_authors":["Barrett BS","Guo K","Hasenkrug KJ","Smith DS","Halemano K","Santiago ML","Heilman KJ"],"view_count":["54"],"additional_accession":[]},"is_claimable":false,"name":"Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection.","description":"Somatic hypermutation (SHM) is an integral process in the development of high-affinity antibodies that are important for recovery from viral infections and vaccine-induced protection. Ig SHM occurs predominantly in germinal centers (GC) via the enzymatic activity of activation-induced deaminase (AID). In contrast, the evolutionarily related apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 3 (APOBEC3) proteins are known to restrict retroviruses, including HIV-1. We previously reported that mouse APOBEC3 encodes Recovery from Friend virus 3 (Rfv3), a classical resistance gene in mice that promotes the neutralizing antibody response against retrovirus infection. We now show that APOBEC3/Rfv3 complements AID in driving Ig SHM during retrovirus infection. Analysis of antibody sequences from retrovirus-specific hybridomas and GC B cells from infected mice revealed Ig heavy-chain V genes with significantly increased C-to-T and G-to-A transitions in wild-type as compared with APOBEC3-defective mice. The context of the mutations was consistent with APOBEC3 but not AID mutational activity. These findings help explain the role of APOBEC3/Rfv3 in promoting the neutralizing antibody responses essential for recovery from retroviral infection and highlight APOBEC3-mediated deamination as a previously unidentified mechanism for antibody diversification in vivo.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 May","modification":"2020-11-19T11:58:16Z","creation":"2019-03-27T01:29:14Z"},"accession":"S-EPMC4040588","cross_references":{"pubmed":["24821801"],"doi":["10.1073/pnas.1403361111"]}}