{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:51:42Z","timestamp":1787824302856,"version":"build-2784847793"},"reference-count":119,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001258","name":"Roche Organ Transplant Research Foundation","doi-asserted-by":"publisher","award":["652596623"],"award-info":[{"award-number":["652596623"]}],"id":[{"id":"10.13039\/501100001258","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI097710"],"award-info":[{"award-number":["R21 AI097710"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The John Faunce &amp; Alicia Tracy Roach Fund","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Albany Medical College Bridge Grant Program","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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 molecule LY2603618 and by siRNA-mediated knockdown. Inhibition of Chk1 resulted in decreased replication of BKPyV DNA and viral spread. Activation of mitotic pathways was associated with the reduction in BKPyV replication. Chk1 inhibitors that are found to be safe and effective in clinical trials for cancer should also be evaluated for antiviral activity against BKPyV.<\/jats:p>","DOI":"10.3390\/v13071353","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Lydia E.","family":"Hainley","sequence":"first","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina S.","family":"Hughson","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3774-7808","authenticated-orcid":false,"given":"Amithi","family":"Narendran","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brody School of Medicine, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8114-0862","authenticated-orcid":false,"given":"Justin","family":"Arthur","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brody School of Medicine, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alida","family":"Hayner-Buchan","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, Berkshire Medical Center, Pittsfield, MA 01201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Surgery, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brody School of Medicine, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1128\/CMR.00074-16","article-title":"BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies","volume":"30","author":"Ambalathingal","year":"2017","journal-title":"Clin. 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