{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:44:07Z","timestamp":1767865447450,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Plan of China","award":["2021YFC2300700"],"award-info":[{"award-number":["2021YFC2300700"]}]},{"name":"National Key Research and Development Plan of China","award":["2022YFC2303300"],"award-info":[{"award-number":["2022YFC2303300"]}]},{"name":"National Key Research and Development Plan of China","award":["XDB0490000"],"award-info":[{"award-number":["XDB0490000"]}]},{"name":"National Key Research and Development Plan of China","award":["31970165"],"award-info":[{"award-number":["31970165"]}]},{"name":"National Key Research and Development Plan of China","award":["31701207"],"award-info":[{"award-number":["31701207"]}]},{"name":"National Key Research and Development Plan of China","award":["2022BCA044"],"award-info":[{"award-number":["2022BCA044"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["2021YFC2300700"],"award-info":[{"award-number":["2021YFC2300700"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["2022YFC2303300"],"award-info":[{"award-number":["2022YFC2303300"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDB0490000"],"award-info":[{"award-number":["XDB0490000"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["31970165"],"award-info":[{"award-number":["31970165"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["31701207"],"award-info":[{"award-number":["31701207"]}]},{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["2022BCA044"],"award-info":[{"award-number":["2022BCA044"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2300700"],"award-info":[{"award-number":["2021YFC2300700"]}],"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":["2022YFC2303300"],"award-info":[{"award-number":["2022YFC2303300"]}],"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":["XDB0490000"],"award-info":[{"award-number":["XDB0490000"]}],"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":["31970165"],"award-info":[{"award-number":["31970165"]}],"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":["31701207"],"award-info":[{"award-number":["31701207"]}],"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":["2022BCA044"],"award-info":[{"award-number":["2022BCA044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key research and development program by Hubei province of China","award":["2021YFC2300700"],"award-info":[{"award-number":["2021YFC2300700"]}]},{"name":"Key research and development program by Hubei province of China","award":["2022YFC2303300"],"award-info":[{"award-number":["2022YFC2303300"]}]},{"name":"Key research and development program by Hubei province of China","award":["XDB0490000"],"award-info":[{"award-number":["XDB0490000"]}]},{"name":"Key research and development program by Hubei province of China","award":["31970165"],"award-info":[{"award-number":["31970165"]}]},{"name":"Key research and development program by Hubei province of China","award":["31701207"],"award-info":[{"award-number":["31701207"]}]},{"name":"Key research and development program by Hubei province of China","award":["2022BCA044"],"award-info":[{"award-number":["2022BCA044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Mammalian arenaviruses are rodent-borne zoonotic viruses, some of which can cause fatal hemorrhagic diseases in humans. The first discovered arenavirus, lymphocytic choriomeningitis virus (LCMV), has a worldwide distribution and can be fatal for transplant recipients. However, no FDA-approved drugs or vaccines are currently available. In this study, using a quantitative proteomic analysis, we identified a variety of host factors that could be needed for LCMV infection, among which we found that protein disulfide isomerase A4 (PDIA4), a downstream factor of endoplasmic reticulum stress (ERS), is important for LCMV infection. Biochemical analysis revealed that LCMV glycoprotein was the main viral component accounting for PDIA4 upregulation. The inhibition of ATF6-mediated ERS could prevent the upregulation of PDIA4 that was stimulated by LCMV infection. We further found that PDIA4 can affect the LCMV viral RNA synthesis processes and release. In summary, we conclude that PDIA4 could be a new target for antiviral drugs against LCMV.<\/jats:p>","DOI":"10.3390\/v15122343","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:48:24Z","timestamp":1701229704000},"page":"2343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Mengwei","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqin","family":"Jian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runming","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gengfu","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-2571","authenticated-orcid":false,"given":"Leike","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100000, China"},{"name":"Hubei Jiangxia Laboratory, Wuhan 430200, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-7277","authenticated-orcid":false,"given":"Hongbo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.3201\/eid2812.220980","article-title":"Highly Diverse Arenaviruses in Neotropical Bats, Brazil","volume":"28","author":"Fischer","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.81.2105.439.b","article-title":"Meningitis in man caused by a filterable virus","volume":"81","author":"Rivers","year":"1935","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.3390\/v4102031","article-title":"Pathogenesis of Lassa fever","volume":"4","author":"Yun","year":"2012","journal-title":"Viruses"},{"key":"ref_4","unstructured":"Centers for Disease Control and Prevention (2006). Survey of lymphocytic choriomeningitis virus diagnosis and testing\u2013Connecticut, 2005. MMWR Morb. Mortal. Wkly. Rep., 55, 398\u2013399."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Sobrido, L., and de la Torre, J.C. (2016). Reporter-Expressing, Replicating-Competent Recombinant Arenaviruses. Viruses, 8.","DOI":"10.3390\/v8070197"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1128\/JVI.01782-10","article-title":"Role of the host cell\u2019s unfolded protein response in arenavirus infection","volume":"85","author":"Pasqual","year":"2011","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12241","DOI":"10.1128\/JVI.75.24.12241-12251.2001","article-title":"Transcription and RNA replication of tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes","volume":"75","year":"2001","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1111\/j.1742-4658.2010.07793.x","article-title":"A structural overview of the PDI family of proteins","volume":"277","author":"Kozlov","year":"2010","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fcell.2015.00030","article-title":"Novel roles for protein disulphide isomerase in disease states: A double edged sword?","volume":"3","author":"Parakh","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41573-021-00320-3","article-title":"Pharmacological targeting of endoplasmic reticulum stress in disease","volume":"21","author":"Marciniak","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s12035-014-9029-6","article-title":"Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries","volume":"53","author":"Nakka","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1161\/CIRCRESAHA.116.310266","article-title":"ATF6 Decreases Myocardial Ischemia\/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart","volume":"120","author":"Jin","year":"2017","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1006892","DOI":"10.1371\/journal.ppat.1006892","article-title":"Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+\/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses","volume":"14","author":"Iwasaki","year":"2018","journal-title":"PLoS Pathog."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e11668","DOI":"10.15252\/emmm.201911668","article-title":"Pdia4 regulates \u03b2-cell pathogenesis in diabetes: Molecular mechanism and targeted therapy","volume":"13","author":"Kuo","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.tibs.2018.06.005","article-title":"Quality Control in the Endoplasmic Reticulum: Crosstalk between ERAD and UPR pathways","volume":"43","author":"Hwang","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.virusres.2018.01.010","article-title":"Protein disulfide isomerases as potential therapeutic targets for influenza A and B viruses","volume":"247","author":"Kim","year":"2018","journal-title":"Virus Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1080\/15548627.2022.2031381","article-title":"Protein disulfide isomerases (PDIs) negatively regulate ebolavirus structural glycoprotein expression in the endoplasmic reticulum (ER) via the autophagy-lysosomal pathway","volume":"18","author":"Wang","year":"2022","journal-title":"Autophagy"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aguilar-Hern\u00e1ndez, N., Meyer, L., L\u00f3pez, S., DuBois, R.M., and Arias, C.F. (2020). Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry. Viruses, 13.","DOI":"10.3390\/v13010053"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1038\/onc.2017.156","article-title":"Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway","volume":"36","author":"Kuo","year":"2017","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/cas.15290","article-title":"Suppression of non-small-cell lung cancer A549 tumor growth by an mtDNA mutation-targeting pyrrole-imidazole polyamide-triphenylphosphonium and a senolytic drug","volume":"113","author":"Tsuji","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105090","DOI":"10.1016\/j.isci.2022.105090","article-title":"Visualizing lymphocytic choriomeningitis virus infection in cells and living mice","volume":"25","author":"Wen","year":"2022","journal-title":"iScience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1021\/acsinfecdis.0c00486","article-title":"High-Throughput Screening of an FDA-Approved Drug Library Identifies Inhibitors against Arenaviruses and SARS-CoV-2","volume":"7","author":"Wan","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2119676119","DOI":"10.1073\/pnas.2119676119","article-title":"CD164 is a host factor for lymphocytic choriomeningitis virus entry","volume":"119","author":"Bakkers","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1146\/annurev-virology-091919-104458","article-title":"Quantitative Temporal Viromics","volume":"8","author":"Weekes","year":"2021","journal-title":"Annu. Rev. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Di Conza, G., and Ho, P.-C. (2020). ER Stress Responses: An Emerging Modulator for Innate Immunity. Cells, 9.","DOI":"10.3390\/cells9030695"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109688","DOI":"10.1016\/j.biopha.2019.109688","article-title":"PDIA4: The basic characteristics, functions and its potential connection with cancer","volume":"122","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bbrc.2022.01.115","article-title":"PDIA4 promotes glioblastoma progression via the PI3K\/AKT\/m-TOR pathway","volume":"597","author":"Wang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2343\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:12Z","timestamp":1760131992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["v15122343"],"URL":"https:\/\/doi.org\/10.3390\/v15122343","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,29]]}}}