Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining.
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 tis...
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Public Library of Science (PLoS)
2021-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009812&type=printable |
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| author | Lulu Yu Vladimir Majerciak Xiang-Yang Xue Aayushi Uberoi Aayushi Uberoi Alexei Lobanov Xiongfong Chen Maggie Cam Stephen H Hughes Paul F Lambert Zhi-Ming Zheng |
| author_facet | Lulu Yu Vladimir Majerciak Xiang-Yang Xue Aayushi Uberoi Aayushi Uberoi Alexei Lobanov Xiongfong Chen Maggie Cam Stephen H Hughes Paul F Lambert Zhi-Ming Zheng |
| author_sort | Lulu Yu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-46e09fb244e243b39563baa1fec48547 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-46e09fb244e243b39563baa1fec485472025-08-20T03:08:32ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-08-01178e100981210.1371/journal.ppat.1009812Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining.Lulu YuVladimir MajerciakXiang-Yang XueAayushi UberoiAayushi UberoiAlexei LobanovXiongfong ChenMaggie CamStephen H HughesPaul F LambertZhi-Ming ZhengMmuPV1 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009812&type=printable |
| spellingShingle | Lulu Yu Vladimir Majerciak Xiang-Yang Xue Aayushi Uberoi Aayushi Uberoi Alexei Lobanov Xiongfong Chen Maggie Cam Stephen H Hughes Paul F Lambert Zhi-Ming Zheng Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. PLoS Pathogens |
| title | Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. |
| title_full | Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. |
| title_fullStr | Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. |
| title_full_unstemmed | Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. |
| title_short | Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining. |
| title_sort | mouse papillomavirus type 1 mmupv1 dna is frequently integrated in benign tumors by microhomology mediated end joining |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009812&type=printable |
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