{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:45:45Z","timestamp":1791945945059,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The coronavirus disease 2019 (COVID\u201019), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), has become a global pandemic with over 778 million confirmed cases and over 7 million deaths. Chronic obstructive pulmonary disease (COPD) mainly developed by cigarette smoke (CS), is considered as a risk factor for COVID\u201019 severe symptoms. However, there is a gap in our knowledge of host\u2010viral interactions for susceptibility to SARS\u2010CoV\u20102 infection and disease severity. Equal numbers (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914) of K18\u2010h (angiotensin\u2010converting enzyme) ACE2 transgenic mice were randomized for sham air (SA) exposure as control group or CS group (2\u2010h CS exposure per day) for 7 days. On Day 8, mice were randomly subdivided into mock infection (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096) and SARS\u2010CoV\u20102 infection (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) for 3 days. Lung tissues were harvested after sacrifice for analysis of viral susceptibility, morphological changes, host immune response, and endoplasmic reticulum (ER) stress. CS exposure increased viral susceptibility by upregulating virus binding receptors ACE2 and binding immunoglobulin protein (BiP), subsequently causing ER stress via activation of activating transcription factor (ATF)6 pathway and protein kinase R (PKR) pathway, resulting in greater immune response and apoptosis. Prior CS exposure caused further deterioration of SARS\u2010CoV\u20102\u2010induced epithelial damage via the loss of epithelial junctions, ciliary dysfunction, mucus hypersecretion, and lung fibrosis. The current findings suggest that ER stress is likely to play a role in the deterioration of SARS\u2010CoV\u20102\u2010induced lung injury prior CS exposure. This study provides a better understanding of the pathogenesis of SARS\u2010CoV\u20102 infection in smokers and possible therapeutic targets for treatment.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70671","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T14:30:47Z","timestamp":1761834647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cigarette Smoke Deteriorates SARS\u2010CoV\u20102 Infection\u2010Induced Lung Injury"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-9053","authenticated-orcid":false,"given":"Rui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"},{"name":"Centre for Immunology and Infection, Hong Kong Science Park Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-0535","authenticated-orcid":false,"given":"Kenrie P. Y.","family":"Hui","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hong Kong Science Park Hong Kong China"},{"name":"School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7217-7444","authenticated-orcid":false,"given":"John M.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8692-6933","authenticated-orcid":false,"given":"Mary S. M.","family":"Ip","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-5995","authenticated-orcid":false,"given":"Malik","family":"Peiris","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hong Kong Science Park Hong Kong China"},{"name":"School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-8405","authenticated-orcid":false,"given":"Michael C. W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hong Kong Science Park Hong Kong China"},{"name":"School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-1313","authenticated-orcid":false,"given":"Judith C. W.","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"},{"name":"Department of Pharmacology &amp; Pharmacy Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"WHO\u201cWHO Coronavirus (COVID\u201019) Dashboard \u201d (2025) https:\/\/covid19.who.int\/ Accessed June 1 2025."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.03.019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02108-2020"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.18332\/tid\/119324"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.51871"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2006.06.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00175"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0732-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0221OC"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00296"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph13060132"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/v8070184"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-023-02008-z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202003-0693LE"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202003-0541OC"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.09.028"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0210ST"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.05.012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02415.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.05.008"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.621441"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.09.018"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104649"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11956"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-213738"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05639.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80330-5"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00108-8"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2359"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-021-01230-4"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00611-0"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03154"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1997.17.503"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2199"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2021-217561"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2021.1883965"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24521-x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110064"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-018-0802-x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201507-427AW"},{"issue":"2","key":"e_1_2_11_43_1","first-page":"233","article-title":"The Management of Pulmonary Fibrosis in COVID\u201019","volume":"53","author":"Rumende C. M.","year":"2021","journal-title":"Acta Medica Indonesiana"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2015.00059"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487320932695"},{"issue":"3","key":"e_1_2_11_46_1","article-title":"Post\u2010COVID\u201019 Pulmonary Fibrosis","volume":"14","author":"Mohammadi A.","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14010051"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6175964"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0778-2"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70671","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.70671","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:20:19Z","timestamp":1791944419000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.70671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":48,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jmv.70671"],"URL":"https:\/\/doi.org\/10.1002\/jmv.70671","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70671"}}