Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining
Fig 9
Proposed model of the role of integrated MmuPV1 DNA in tumorigenesis.
After virus infection, MmuPV1 induction of the host DNA damage response and activation of the cellular DNA repair machinery enhance the breakage and recombination of both the viral and host genomes. The linearized viral genomes (vDNA) could be fused to any nicked or damaged region of the host genome (hDNA) most likely by a microhomology-mediated DNA repair pathway (A). MmuPV1 integration into the host genomic DNA appears to be mostly random; however, what we detected in our experiments was modified by post-integration selection. Integrated MmuPV1 DNA accumulates over time following MmuPV1 infection, contributing to tumor formation. Clonal expansion of cells that express viral E6 and E7 from the integrated MmuPV1 DNA through the linearized E2 region [14–16], leads to tumor progression and ultimately to cancer (B).