{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:52:58Z","timestamp":1781679178437,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007288","name":"Mahasarakham University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Human herpesvirus 6 (HHV-6) establishes lifelong latency after primary infection and may reactivate under conditions of immune modulation. Tumor necrosis factor alpha (TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ) is a key pro-inflammatory cytokine involved in antiviral responses, and functional variation in the\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      promoter (\u2212308G\u202f&amp;gt;\u202fA, rs1800629) may influence host\u2013virus equilibrium. However, population-based data examining host genetic determinants of HHV-6 detection in Southeast Asia remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a community-based cross-sectional study of 852 participants aged 3\u201390\u202fyears in Phayao Province, Thailand. HHV-6 DNA was detected by nested PCR and quantitative PCR. Genotyping of\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      (rs1800629) and additional polymorphisms was performed using high-resolution melt analysis with sequencing validation. Sociodemographic, clinical, and psychological variables were assessed using standardized questionnaires. Multivariable logistic regression was used to evaluate independent predictors of HHV-6 positivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HHV-6 DNA was detected in 12.8% of participants and increased with age (adjusted OR per 10-year increase 1.55, 95% CI 1.35\u20131.78;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). The\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      (\u2212308G\u202f&amp;gt;\u202fA) polymorphism was independently associated with HHV-6 detection (adjusted OR 3.21, 95% CI 1.98\u20135.20;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Lower education level also remained significant (adjusted OR 3.88, 95% CI 1.35\u201311.15;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.012). The\n                      <jats:italic>DAT1<\/jats:italic>\n                      (rs40184) genotype showed a modest association in the full model (adjusted OR 1.84, 95% CI 1.02\u20133.32;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.041) but was borderline in adult-only sensitivity analysis. Psychological measures were not independently associated with HHV-6 positivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this Thai community cohort, the\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      (\u2212308G\u202f&amp;gt;\u202fA) promoter variant was independently associated with HHV-6 DNA detection. These findings support an observational model in which host immunogenetic variation contributes to inter-individual differences in viral DNA detection, although longitudinal studies are required to clarify causal mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1825548","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:55:47Z","timestamp":1781675747000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between TNF-\u03b1 (\u2212308G\u202f&gt;\u202fA) promoter polymorphism and HHV-6 DNA detection in a community-based Thai cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Sureewan","family":"Bumrungthai","sequence":"first","affiliation":[{"name":"Division of Biopharmacy, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University","place":["Ubon Ratchathani, Thailand"]},{"name":"Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao","place":["Phayao, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutida","family":"Pongpukdeesakul","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao","place":["Phayao, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tipaya","family":"Ekalaksananan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Khon Kaen University","place":["Khon Kaen, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureewan","family":"Duangjit","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University","place":["Ubon Ratchathani, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamsai","family":"Pientong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Khon Kaen University","place":["Khon Kaen, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuchsupha","family":"Sunthamala","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Mahasarakham University","place":["Mahasarakham, Thailand"]},{"name":"Epidemic Simulation and Aetiology Nexus for Infectious Diseases, Mahasarakham University","place":["Mahasarakham, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.mgene.2016.06.002","article-title":"TNF-\u03b1 - 308 G > a and IFN-\u03b3 + 874 a > T gene polymorphisms in Egyptian patients with lupus erythematosus","volume":"9","author":"Al-Kholy","year":"2016","journal-title":"Meta Gene"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"CMAMD.S6941","DOI":"10.4137\/CMAMD.S6941","article-title":"TNF-\u03b1 and TNF-\u03b2 gene polymorphism in Saudi rheumatoid arthritis patients","volume":"4","author":"Al-Rayes","year":"2011","journal-title":"Clin. Med. Insights Arthritis Musculoskelet. Disord."},{"key":"ref3","volume-title":"StatPearls [Internet]","author":"Bains","year":"2024"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1093\/clinchem\/46.7.1000","article-title":"Genotyping of HLA-B27 by real-time PCR without hybridization probes","volume":"46","author":"Bon","year":"2000","journal-title":"Clin. Chem."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3892\/br.2024.1869","article-title":"Association of HHV-6 reactivation and SLC6A3 (C>T, rs40184), BDNF (C>T, rs6265), and JARID2 (G>a, rs9383046) single nucleotide polymorphisms in depression","volume":"21","author":"Bumrungthai","year":"2024","journal-title":"Biomed. Rep."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.tem.2012.11.005","article-title":"The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore","volume":"24","author":"Busillo","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune regulation by glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref8","first-page":"2473","article-title":"A novel relationship for schizophrenia, bipolar and major depressive disorder part 5: a hint from chromosome 5 high density association screen","volume":"9","author":"Chen","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1097\/01.inf.0000165397.48153.3f","article-title":"Virological and clinical features of human herpesvirus-6 infection in Korean children","volume":"24","author":"Choi","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e04273","DOI":"10.1016\/j.heliyon.2020.e04273","article-title":"Prevalence of and factors associated with depression among hill tribe individuals aged 30 years and over in Thailand","volume":"6","author":"Chomchoei","year":"2020","journal-title":"Heliyon"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1001\/archinte.159.20.2430","article-title":"Persistent stress as a predictor of genital herpes recurrence","volume":"159","author":"Cohen","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1128\/JCM.40.7.2445-2451","article-title":"Real-time PCR for quantification of human herpesvirus 6 DNA from lymph nodes and saliva","volume":"40","author":"Collot","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12026-014-8517-0","article-title":"Effects of stress on immune function: the good, the bad, and the beautiful","volume":"58","author":"Dhabhar","year":"2014","journal-title":"Immunol. Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.psyneuen.2012.05.008","article-title":"McEwen.Stress-induced redistribution of immune cells-from barracks to boulevards to battlefields: a tale of three hormones","volume":"37","author":"Dhabhar","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"ref16","first-page":"2636","article-title":"Development and validation of high resolution melting assays for high-throughput screening of BDNF rs6265 and DAT1 rs40184","volume":"14","author":"Faris","year":"2018","journal-title":"Malay. J. Med. Health Sci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"433","DOI":"10.31887\/DCNS.2006.8.4\/mising","article-title":"Genetics of stress response and stress-related disorders","volume":"8","author":"Ising","year":"2006","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1007\/s40588-023-00202-9","article-title":"Intimate relationship between stress and human alpha herpes virus 1 (HSV 1) reactivation from latency","volume":"10","author":"Jones","year":"2023","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08259-7","article-title":"Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms","volume":"10","author":"Jones","year":"2019","journal-title":"Nat Commun."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"5441","DOI":"10.4049\/jimmunol.160.11.5441","article-title":"Role of the hypothalmic pituitary adrenal axis and IL-6 in stress-induced reactivation of latent herpes simplex virus type 1","volume":"160","author":"Noisakran","year":"1998","journal-title":"J. Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.jaci.2013.09.007","article-title":"The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease","volume":"132","author":"Oakley","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"7231","DOI":"10.1073\/pnas.95.12.7231","article-title":"Social stress and the reactivation of latent herpes simplex virus type 1","volume":"95","author":"Padgett","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref24","author":"Paramee","year":"2026"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"835","DOI":"10.4238\/vol9-2gmr767","article-title":"Association of C\/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population","volume":"9","author":"Pattarachotanant","year":"2010","journal-title":"Genet. Mol. Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1002\/rmv.715","article-title":"Chromosomally integrated human herpesvirus 6: questions and answers","volume":"22","author":"Pellett","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3390\/w15020323","article-title":"Human oncogenic Epstein\u2013Barr virus in water and human blood infection of communities in Phayao Province, Thailand","volume":"15","author":"Pongpakdeesakul","year":"2023","journal-title":"Water"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1056\/NEJMra050541","article-title":"Antiinflammatory action of glucocorticoids - new mechanisms of old drugs","volume":"353","author":"Rhen","year":"2005","journal-title":"New England J Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-\u03b3: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.3390\/v15091898","article-title":"The association of HHV-6 and the TNF-\u03b1 (\u2212308G\/a) promotor with major depressive disorder patients and healthy controls in Thailand","volume":"15","author":"Sumala","year":"2023","journal-title":"Viruses"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.7600\/jpfsm.11.43","article-title":"Variabilities of salivary human herpesvirus 6\/7 and cortisol levels during a three-day training camp in judo athletes","volume":"11","author":"Tamai","year":"2022","journal-title":"J. Physic. Fitness Sports Med."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s44197-023-00121-4","article-title":"Aetiology of acute undifferentiated fever among children under the age of five in Vietnam: a prospective study","volume":"13","author":"Tran","year":"2023","journal-title":"J Epidemiol Glob Health"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.3390\/cancers11071037","article-title":"AP-1 transcription factors as regulators of immune responses in cancer","volume":"11","author":"Vasileios","year":"2019","journal-title":"Cancer"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1128\/JCM.44.4.1571-1574","article-title":"Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles","volume":"44","author":"Ward","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1093\/infdis\/162.5.1014","article-title":"Seroepidemiological and virological evidence for human herpesvirus-6 infection in infants and children","volume":"162","author":"Yamanishi","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.neulet.2014.07.004","article-title":"No association of SLC6A3 and SLC6A4 gene polymorphisms with schizophrenia in the Han Chinese population","volume":"2014579","author":"Yang","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"494","DOI":"10.2174\/1570159x1304150831150507","article-title":"The effects of psychological stress on depression","volume":"13","author":"Yang","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","article-title":"Cytokines, inflammation and pain","volume":"45","author":"Zhang","year":"2007","journal-title":"Int. Anesthesiol. Clin."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/jmv.10419","article-title":"Prevalence of human herpesvirus-6 and -7 infection in healthy Chinese adults: evidence of viral DNA persistence in peripheral blood","volume":"70","author":"Zhang","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12985-021-01510-6","article-title":"A multiplex real-time PCR quantitation of human herpesvirus-6, 7, 8 viruses: application in blood transfusions","volume":"18","author":"Zheng","year":"2021","journal-title":"Virol. J."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1825548\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:55:49Z","timestamp":1781675749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1825548\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":40,"alternative-id":["10.3389\/fmicb.2026.1825548"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1825548","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"article-number":"1825548"}}