{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:47Z","timestamp":1787028467569,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL141364"],"award-info":[{"award-number":["HL141364"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL122383"],"award-info":[{"award-number":["HL122383"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL136917"],"award-info":[{"award-number":["HL136917"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL076122"],"award-info":[{"award-number":["HL076122"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Pathology and Laboratory Medicine, The University of Vermont, USA","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Influenza (IAV) neuraminidase (NA) is a glycoprotein required for the viral exit from the cell. NA requires disulfide bonds for proper function. We have recently demonstrated that protein disulfide isomerase (PDI)A3 is required for oxidative folding of IAV hemagglutinin (HA), and viral propagation. However, it not known whether PDIs are required for NA maturation or if these interactions represent a putative target for the treatment of influenza infection. We sought to determine whether PDIA3 is required for disulfide bonds of NA, its activity, and propagation of the virus. Requirement of disulfides for NA oligomerization and activity were determined using biotin switch and redox assays in WT and PDIA3\u2212\/\u2212 in A549 cells. A PDI specific inhibitor (LOC14) was utilized to determine the requirement of PDIs in NA activity, IAV burden, and inflammatory response in A549 and primary mouse tracheal epithelial cells. Mice were treated with the inhibitor LOC14 and subsequently examined for IAV burden, NA activity, cytokine, and immune response. IAV-NA interacts with PDIA3 and this interaction is required for NA activity. PDIA3 ablation or inhibition decreased NA activity, viral burden, and inflammatory response in lung epithelial cells. LOC14 treatment significantly attenuated the influenza-induced inflammatory response in mice including the overall viral burden. These results provide evidence for PDIA3 inhibition suppressing NA activity, potentially providing a novel platform for host-targeted antiviral therapies.<\/jats:p>","DOI":"10.3390\/ijms23031078","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T21:01:51Z","timestamp":1642626111000},"page":"1078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Protein Disulfide Isomerase A3 Regulates Influenza Neuraminidase Activity and Influenza Burden in the Lung"],"prefix":"10.3390","volume":"23","author":[{"given":"Nicolas","family":"Chamberlain","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Ruban","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe F.","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra R.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravishankar","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhemerson","family":"Souza De Lima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Antos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pulmonary Medicine, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Nakada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pulmonary Medicine, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Anathy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jung, H.E., and Lee, H.K. 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