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HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome.

Abstract：

:Many viruses subvert the host cell's ability to mount and complete various DNA damage responses (DDRs) after infection. HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication, but the DDRs remain uncompleted without arrest or apoptosis. We believe this was in part due to partitioning of the damage response and double strand break repair components. After extraction of soluble proteins, the localization of these components fell into three groups: specifically associated with the viral replication centers (RCs), diffused throughout the nucleoplasm and excluded from the RCs. Others have shown that cells are incapable of processing exogenously introduced damage after infection. We hypothesized that the inability of the cells to process damage might be due to the differential association of repair components within the RCs and, in turn, potentially preferential repair of the viral genome and compromised repair of the host genome. To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts. Comet assays indicated that repair was initiated, but was not completed in infected cells. Quantitative analysis of immunofluorescent localization of cyclobutane pyrimidine dimers (CPDs) revealed that after 24 h of repair, CPDs were significantly reduced in viral DNA, but not significantly changed in the infected host DNA. To further quantitate CPD repair, we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously. Combining this Southern methodology with a CPD-specific T4 endonuclease V alkaline agarose assay to quantitate repair of adducts, we found efficient repair of CPDs from the viral DNA but not host cellular DNA. Our data confirm that NER functions in HCMV-infected cells and almost exclusively repairs the viral genome to the detriment of the host's genome.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

O'Dowd JM,Zavala AG,Brown CJ,Mori T,Fortunato EA

doi

10.1371/journal.ppat.1003038

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

e1003038

issue

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-12-00842

journal_volume

pub_type

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HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome.