{"doi":"10.1101/2023.11.02.565355","title":"Apobec-Mediated Retroviral Hypermutation <i>In Vivo</i> is Dependent on Mouse Strain","abstract":"Abstract Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) during viral replication in BALB/c mice. To further study the role of Rem in vivo , we have infected C57BL/6 (B6) mice with a superantigen-independent lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain (TBLV-SD) that is defective in Rem and its cleavage product Rem-CT. Unlike MMTV, TBLV induced T-cell tumors in µMT mice, indicating that mature B cells, which express the highest AID levels, are not required for TBLV replication. Compared to BALB/c, B6 mice were more susceptible to TBLV infection and tumorigenesis. The lack of Rem expression accelerated B6 tumorigenesis at limiting doses compared to TBLV-WT in either wild-type B6 or AID-deficient mice. However, unlike proviruses from BALB/c mice, high-throughput sequencing indicated that proviral G-to-A or C-to-T changes did not significantly differ in the presence and absence of Rem expression. Ex vivo stimulation showed higher levels of mA3 relative to AID in B6 compared to BALB/c splenocytes, but effects of agonists differed in the two strains. RNA-Seq revealed increased transcripts related to growth factor and cytokine signaling in TBLV-SD-induced tumors relative to those from TBLV-WT, consistent with a third Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":413611,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1195183,"name":"Gurvani B. Singh","orcid":null,"position":1,"is_corresponding":false},{"id":355976,"name":"Wendy Kaichun Xu","orcid":"0000-0002-5866-3523","position":2,"is_corresponding":false},{"id":747021,"name":"Das P","orcid":"0000-0002-8100-7962","position":3,"is_corresponding":false},{"id":259138,"name":"Alejandro Reyes","orcid":"0000-0003-2907-3265","position":4,"is_corresponding":false},{"id":552408,"name":"Anna Battenhouse","orcid":"0000-0002-7455-9064","position":5,"is_corresponding":false},{"id":21508,"name":"Dennis Wylie","orcid":"0000-0003-0380-3549","position":6,"is_corresponding":false},{"id":823174,"name":"Mary M. Lozano","orcid":null,"position":7,"is_corresponding":false},{"id":355977,"name":"Jaquelin P. Dudley","orcid":"0000-0002-1581-1098","position":8,"is_corresponding":false},{"id":357437,"name":"Hyewon Byun","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","pmid":"37961113","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}