{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:24:52Z","timestamp":1777944292016,"version":"3.51.4"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007123","name":"Stanley Medical Research Institute","doi-asserted-by":"publisher","award":["07-1690"],"award-info":[{"award-number":["07-1690"]}],"id":[{"id":"10.13039\/100007123","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Herpesviruses are recognized as major causes of human diseases. Following initial infection, Herpesviruses can undergo cycles of reactivation controlled largely by the immune system. Cigarette smoking is an important modulator of the immune system particularly in individuals with serious mental illness where smoking is associated with increased rates of cardiopulmonary diseases and mortality. However, the effect of smoking on Herpesviruses has not been extensively studied.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this nested cohort study, cigarette smoking was assessed in 1323 persons with serious mental illness or without a psychiatric disorder ascertained in a psychiatric health care system and the adjacent community. Participants provided a blood sample from which were measured IgG class antibodies to five human Herpesviruses: Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus-Type 1 (HSV-1); Varicella Zoster Virus (VZV); and Human Herpes Virus-Type 6 (HHV-6). The associations between smoking variables and antibody levels to the Herpesviruses were analyzed among diagnostic groups in multiple regression models adjusted for age, sex, and race.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Current smoking was significantly associated with higher levels of antibodies to CMV (coefficient .183, 95% CI .049, .317, p&lt;.001, q&lt;.007) and the three EBV proteins (EBV NA \u2013(coefficient .088, 95% CI .032, .143, p = .002, q&lt;.014; EBV Virion \u2013 coefficient .100, 95% CI .037, .163, p = .002, q&lt;.014; and EBV VCA \u2013 coefficient .119, 95% CI .061, .177, p = .00004, q&lt;.0016). The amount of cigarettes smoked was also correlated with higher levels of antibodies to the three EBV proteins. Interaction analyses indicated that the association between cigarette smoking and levels of antibodies to CMV and EBV was independent of diagnostic group. Cigarette smoking was not significantly associated with the level of antibodies to HSV-1, VZV, or HHV-6.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Individuals who smoke cigarettes have increased levels of IgG antibodies to CMV and EBV. Cigarette smoking may be a contributory factor in the relationship between CMV, EBV and chronic somatic disorders associated with these viruses.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0280443","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T18:43:17Z","timestamp":1674067397000},"page":"e0280443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cigarette smoking is associated with Herpesviruses in persons with and without serious mental 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Idiopathic Pulmonary Fibrosis?","volume":"18","author":"TM Maher","year":"2021","journal-title":"Ann Am Thorac Soc."},{"key":"pone.0280443.ref002","doi-asserted-by":"crossref","first-page":"100117","DOI":"10.1016\/j.jtauto.2021.100117","article-title":"Serologic markers of Epstein-Barr virus reactivation are associated with increased disease activity, inflammation, and interferon pathway activation in patients with systemic lupus erythematosus","volume":"4","author":"RA Wood","year":"2021","journal-title":"J Transl Autoimmun"},{"issue":"2","key":"pone.0280443.ref003","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/infdis\/jiu437","article-title":"Cytomegalovirus infection and risk of Alzheimer disease in older black and white individuals","volume":"211","author":"LL Barnes","year":"2015","journal-title":"J Infect Dis"},{"issue":"1","key":"pone.0280443.ref004","doi-asserted-by":"crossref","first-page":"268","DOI":"10.18632\/oncotarget.13613","article-title":"Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?","volume":"8","author":"F Qiu","year":"2017","journal-title":"Oncotarget"},{"key":"pone.0280443.ref005","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.pharmthera.2018.05.005","article-title":"Autoimmune phenotypes in schizophrenia reveal novel treatment targets","volume":"189","author":"EG Severance","year":"2018","journal-title":"Pharmacol Ther"},{"issue":"2-3","key":"pone.0280443.ref006","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.schres.2008.07.017","article-title":"Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia","volume":"106","author":"BH Shirts","year":"2008","journal-title":"Schizophr Res"},{"issue":"5","key":"pone.0280443.ref007","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1001\/archpsyc.60.5.466","article-title":"Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia","volume":"60","author":"FB Dickerson","year":"2003","journal-title":"Arch Gen Psychiatry"},{"issue":"4","key":"pone.0280443.ref008","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1093\/schbul\/sbt113","article-title":"Mortality in schizophrenia: clinical and serological predictors","volume":"40","author":"F Dickerson","year":"2014","journal-title":"Schizophr Bull"},{"key":"pone.0280443.ref009","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jad.2019.11.150","article-title":"Atypical immune response to Epstein-Barr virus in major depressive disorder","volume":"264","author":"L Jones-Brando","year":"2020","journal-title":"J Affect Disord"},{"issue":"5","key":"pone.0280443.ref010","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/schbul\/sby164","article-title":"Schizophrenia is Associated With an Aberrant Immune Response to Epstein-Barr Virus","volume":"45","author":"F 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Chen","year":"2022","journal-title":"Open Forum Infect Dis"},{"issue":"6578","key":"pone.0280443.ref017","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"K Bjornevik","year":"2022","journal-title":"Science"},{"issue":"2","key":"pone.0280443.ref018","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/msj.20240","article-title":"Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking","volume":"78","author":"DM Wingerchuk","year":"2011","journal-title":"Mt Sinai J Med"},{"issue":"5","key":"pone.0280443.ref019","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/jmv.25389","article-title":"Cytomegalovirus immunoglobulin G titers do not predict reactivation risk in immunocompetent hosts","volume":"91","author":"SA Mansfield","year":"2019","journal-title":"J Med Virol"},{"issue":"3-4","key":"pone.0280443.ref020","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00430-019-00600-1","article-title":"Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades\u2019 r\u00e9sum\u00e9","volume":"208","author":"A Krmpoti\u0107","year":"2019","journal-title":"Med Microbiol Immunol"},{"key":"pone.0280443.ref021","first-page":"6675353","article-title":"Cytomegalovirus Infection and Its Relationship with Leukocyte Telomere Length: A Cross-Sectional Study","volume":"2021","author":"Z Lin","year":"2021","journal-title":"Mediators Inflamm"},{"issue":"12","key":"pone.0280443.ref022","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.bcp.2010.07.001","article-title":"Innate immune response and viral interference strategies developed by human herpesviruses","volume":"80","author":"P Vandevenne","year":"2010","journal-title":"Biochem 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