Unconserved C terminal of human cytomegalovirus tegument protein pUL76 elicits nuclear aggresome formation and induces DNA damage in transfected cells

BACKGROUND: The HCMV UL76 gene is a member of UL24 family in herpes virus and encodes a highly conserved herpes virus protein. Inherited from common ancestor, members of Herpes(_)UL24 family encode proteins with a conserved N terminal and varied in C terminal region. To define which region (conserved N terminal or unconserved C terminal) of UL76 was responsible for its ability to induce DNA damage and aggresome formation, the wild-type UL76 gene and two deletion mutants were transfected to cells and analyzed by immunofluorescent staining, Western blotting and comet assay. RESULTS: We report that the EGFP-fusion proteins present as globular aggresomes and colocalize with γ-H2AX in cells transfected with either pEGFP-UL76 or pEGFP-UL76C. The relative expression level of γ-H2AX and percentage of cells with comet tails were elevated in pEGFP-UL76 or pEGFP-UL76C transfection groups compared to the control. CONCLUSION: Our findings suggest that the unconserved C terminal (not the conserved N terminal) of pUL76 was sufficient to induce DNA damage and aggresome formation in transfected cells.