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Chronic exposure to arsenite enhances influenza virus infection in cultured cells
Author(s) -
Amouzougan Eva A.,
Lira Ricardo,
Klimecki Walter T.
Publication year - 2020
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3918
Subject(s) - arsenite , sodium arsenite , influenza a virus , cell culture , virology , virus , biology , immunology , toxicity , sialic acid , cytotoxicity , arsenic , microbiology and biotechnology , chemistry , medicine , biochemistry , in vitro , organic chemistry , genetics
Abstract Arsenic is a ubiquitous environmental toxicant that has been associated with human respiratory diseases. In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well‐established 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‐Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3‐fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35‐fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite‐exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment‐positive cells (2 hours p.i.) and 224% increase in α‐2,3 sialic acid‐positive 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‐fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A/Udorn/72 (H3N2) infected BEAS‐2B 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‐influenza drug, oseltamivir, in arsenite‐exposed cells raises substantial public health concerns if this effect translates to arsenic‐exposed, influenza‐infected people.

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