741A RM Bock Labs
Parvovirinae are small DNA viruses that are pathogenic in most animals, made up of small linear single-stranded DNA genome, and rely extensively on host nuclear factors, particularly the DNA Damage Response (DDR) machinery that usually protects us from cancer. Upon infection, the parvovirus minute virus of mice (MVM) localizes to cellular sites of DDR to jumpstart its replication in host cells. As it replicates in the host cell nucleus, it continues to induce additional DNA damage through various means, which also serve as sites of viral replication, thereby enabling the virus to amplify in the host nuclear environment. We seek to elucidate the molecular mechanisms by which MVM localizes to cellular DDR sites, induce additional DNA damage and generate chromosomal aberrations. We have developed systems to study where viral genomes localize using genomics and single-cell imaging, inducible DNA damage systems to investigate the cause-effect relationship between the virus and cellular DDR, and have optimized methods to study how viral infection causes chromosomal aberrations. The findings from our work are applicable to understand the biology of small DNA viruses such as HPV and HBV, which are oncogenic, and for gene therapy applications which use modified AAV parvoviruses.