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In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well\u2010established impact of arsenic on epithelial cell biology, we posited that the effect of arsenic exposure in epithelial cells could enhance viral infection. In this study, we characterized influenza virus A\/WSN\/33 (H1N1) infection in Madin\u2010Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3\u2010fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35\u2010fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite\u2010exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment\u2010positive cells (2 hours p.i.) and 224% increase in \u03b1\u20102,3 sialic acid\u2010positive cells. Interestingly, chronic exposure to arsenite reduced the effect of the antiviral drug, oseltamivir in MDCK cells. We also found that exposure to sodium arsenite resulted in a 4.4\u2010fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A\/Udorn\/72 (H3N2) infected BEAS\u20102B cells. This study suggests that chronic arsenite exposure could result in enhanced influenza infection in epithelial cells, and that this may be mediated through increased sialic acid binding. Finally, the decreased effectiveness of the anti\u2010influenza drug, oseltamivir, in arsenite\u2010exposed cells raises substantial public health concerns if this effect translates to arsenic\u2010exposed, influenza\u2010infected people.<\/jats:p>","DOI":"10.1002\/jat.3918","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T01:49:15Z","timestamp":1579571355000},"page":"458-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic exposure to arsenite enhances influenza virus infection in cultured cells"],"prefix":"10.1002","volume":"40","author":[{"given":"Eva A.","family":"Amouzougan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy The University of Arizona  Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Ricardo","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy The University of Arizona  Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-874X","authenticated-orcid":false,"given":"Walter T.","family":"Klimecki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy The University of Arizona  Tucson Arizona"},{"name":"College of Veterinary Medicine The University of Arizona  Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2395211"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.04.030"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141365"},{"key":"e_1_2_6_5_1","unstructured":"Centres W. H. O. C. Cc W. H. O. July R. &Rt\u2010pcr C.(2017).WHO information for the molecular detection of influenza viruses (2017 July). In World Health Organization. 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