{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:43:22Z","timestamp":1791999802690,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81481460305"],"award-info":[{"award-number":["81481460305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31360033"],"award-info":[{"award-number":["31360033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81360259"],"award-info":[{"award-number":["81360259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Alcohol could compromise the anti\u2010hepatitis C virus (HCV) function of interferon\u2010alpha (IFN\u2010\u03b1). However, little information is available about the effect of alcohol on interferon\u2010lambda (IFN\u2010\u03bb, type III IFN), a novel candidate for development of therapy for HCV infection. Huh7 cells were infected with HCV JFH\u20101 virus, then treated with alcohol, and\/or IFN\u2010\u03bb1. RT\u2010PCR and Western blot were used to detect the levels of HCV and key cellular factors. Overexpression or silencing expression was performed to verify the role of key factors in alcohol\u2010attenuated anti\u2010HCV function of IFN\u2010\u03bb1. Alcohol treatment compromised anti\u2010HCV effect of IFN\u2010\u03bb1 in HCV JFH\u20101\u2010infected Huh7 cells, evidenced by the significantly increased levels of HCV RNA, and HCV core protein in alcohol\u2010\/IFN\u2010\u03bb1\u2010treated cells compared to cells with IFN\u2010\u03bb1 treatment alone. Investigation of the mechanisms responsible for the alcohol action revealed that alcohol enhanced the expression of protein inhibitor of activated STAT (PIASy). Overexpression of PIASy compromised anti\u2010HCV ability of IFN\u2010\u03bb1, whereas silencing expression of PIASy partly restored the alcohol\u2010attenuated anti\u2010HCV effect of IFN\u2010\u03bb1. More importantly, overexpression of PIASy significantly down\u2010regulated the level of IFN\u2010\u03bb1\u2010indcued phosphorylation of STAT1 (p\u2010STAT1), an important adaptor in IFN\u2010\u03bb pathway, as well as reduced the expression of IFN\u2010\u03bb1\u2010induced IFN\u2010stimulated genes 56 (ISG56), and myxovirus resistance 1 (Mx1), two antiviral effectors in in IFN\u2010\u03bb pathway. These findings indicate that alcohol, through inducing the expression of negative regulator in IFN\u2010\u03bb pathway, inhibits IFN\u2010\u03bb\u2010mediated anti\u2010HCV action in human hepatic cells, which may lead to the poor efficacy of IFN\u2010\u03bb\u2010based therapy against HCV infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.25053","type":"journal-article","created":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T11:28:43Z","timestamp":1518694123000},"page":"1112-1120","source":"Crossref","is-referenced-by-count":4,"title":["Alcohol attenuates anti\u2010HCV function of IFN\u2010\u03bb1 through up\u2010regulation of PLASy expression in human hepatic cells"],"prefix":"10.1002","volume":"90","author":[{"given":"Meihua","family":"Ran","sequence":"first","affiliation":[{"name":"Geriatrics Digestion Department of Internal Medicine The First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China"},{"name":"Guangxi Key Laboratory of AIDS Prevention and Treatment &amp; 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