Viruses, Vol. 13, Pages 1353: Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection

Viruses, Vol. 13, Pages 1353: Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection Viruses doi: 10.3390/v13071353 Authors: Lydia E. Hainley Martina S. Hughson Amithi Narendran Ralph Smith Justin Arthur Alida Hayner-Buchan David J. Conti John M. Lehman Thomas D. Friedrich The human BK polyomavirus (BKPyV) is latent in the kidneys of most adults, but can be reactivated in immunosuppressed states, such as following renal transplantation. If left unchecked, BK polyomavirus nephropathy (PyVAN) and possible graft loss may result from viral destruction of tubular epithelial cells and interstitial fibrosis. When coupled with regular post-transplant screening, immunosuppression reduction has been effective in limiting BKPyV viremia and the development of PyVAN. Antiviral drugs that are safe and effective in combating BKPyV have not been identified but would be a benefit in complementing or replacing immunosuppression reduction. The present study explores inhibition of the host DNA damage response (DDR) as an antiviral strategy. Immunohistochemical and immunofluorescent analyses of PyVAN biopsies provide evidence for stimulation of a DDR in vivo. DDR pathways were also stimulated in vitro following BKPyV infection of low-passage human renal proximal tubule epithelial cells. The role of Chk1, a protein kinase known to be involved in the replication stress-induced DDR, was examined by inhibition with the small mol...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research