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Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ). Nevertheless, some viroporins are known to disrupt host cell Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in mammalian cells. The goal of this study was to demonstrate that the NSP4 VPD forms an ion channel and determine whether the channel can conduct Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . Using planar lipid bilayer and liposome patch clamp electrophysiology, we show that a synthetic peptide of the NSP4 VPD has ion channel activity. The NSP4 VPD was selective for cations over anions and channel activity was observed to have both well-defined \u201csquare top\u201d openings as well as fast current fluctuations, similar to other viroporins. Importantly, the NSP4 VPD showed similar conductance of divalent cations (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and Ba\n                    <jats:sup>2+<\/jats:sup>\n                    ) as monovalent cations (K\n                    <jats:sup>+<\/jats:sup>\n                    ), but a viroporin defective mutant lacked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    conductivity. These data demonstrate that the NSP4 VPD is a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -conducting viroporin and establish the mechanism by which NSP4 disturbs host cell Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis.\n                  <\/jats:p>","DOI":"10.1038\/srep43487","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T06:54:55Z","timestamp":1488524095000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel"],"prefix":"10.1038","volume":"7","author":[{"given":"Thieng","family":"Pham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob L.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L.","family":"Dosey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne H.","family":"Delcour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Hyser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"BFsrep43487_CR1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1146\/annurev-virology-100114-054846","volume":"2","author":"JM Hyser","year":"2015","unstructured":"Hyser, J. 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