{"doi":"10.1371/journal.ppat.1009812","title":"Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining","abstract":"MmuPV1 is a useful model for studying papillomavirus-induced tumorigenesis. We used RNA-seq to look for chimeric RNAs that map to both MmuPV1 and host genomes. In tumor tissues, a higher proportion of total viral reads were virus-host chimeric junction reads (CJRs) (1.9‰ - 7‰) than in tumor-free tissues (0.6‰ - 1.3‰): most CJRs mapped to the viral E2/E4 region. Although most of the MmuPV1 integration sites were mapped to intergenic regions and introns throughout the mouse genome, integrations were seen more than once in several genes: Malat1, Krt1, Krt10, Fabp5, Pard3, and Grip1; these data were confirmed by rapid amplification of cDNA ends (RACE)-Single Molecule Real-Time (SMRT)-seq or targeted DNA-seq. Microhomology sequences were frequently seen at host-virus DNA junctions. MmuPV1 infection and integration affected the expression of host genes. We found that factors for DNA double-stranded break repair and microhomology-mediated end-joining (MMEJ), such as H2ax, Fen1, DNA polymerase Polθ, Cdk1, and Plk1, exhibited a step-wise increase and Mdc1 a decrease in expression in MmuPV1-infected tissues and MmuPV1 tumors relative to normal tissues. Increased expression of mitotic kinases CDK1 and PLK1 appears to be correlated with CtIP phosphorylation in MmuPV1 tumors, suggesting a role for MMEJ-mediated DNA joining in the MmuPV1 integration events that are associated with MmuPV1-induced progression of tumors.","journal":"PLoS Pathogens","year":2021,"id":171062,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9373,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":328278,"name":"Vladimır Majerčiak","orcid":"0000-0003-2907-4583","position":1,"is_corresponding":false},{"id":501617,"name":"Xiangyang Xue","orcid":"0000-0002-8670-2016","position":2,"is_corresponding":false},{"id":554105,"name":"Aayushi Uberoi","orcid":"0000-0002-2389-5957","position":3,"is_corresponding":false},{"id":328279,"name":"Alexei Lobanov","orcid":"0000-0002-9883-4374","position":4,"is_corresponding":false},{"id":444492,"name":"Xiongfong Chen","orcid":null,"position":5,"is_corresponding":false},{"id":562958,"name":"Maggie Cam","orcid":"0000-0001-8190-9766","position":6,"is_corresponding":false},{"id":258968,"name":"Stephen H. Hughes","orcid":"0000-0002-9176-4377","position":7,"is_corresponding":false},{"id":328282,"name":"Paul F. Lambert","orcid":"0000-0001-7983-2755","position":8,"is_corresponding":false},{"id":219079,"name":"Zhi-Ming Zheng","orcid":"0000-0001-5547-7912","position":9,"is_corresponding":false},{"id":562955,"name":"Lulu Yu","orcid":"0000-0003-0309-9520","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-18T23:46:28.747384Z","pmid":"34343212","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":[]}