{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T19:45:12Z","timestamp":1771875912324,"version":"3.50.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["Grant No. MRG 6080260"],"award-info":[{"award-number":["Grant No. MRG 6080260"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Dengue infection is a leading global public health problem, and the virus (DENV) is transmitted by\n                    <jats:italic>Aedes<\/jats:italic>\n                    mosquitoes and causes a wide spectrum of clinical manifestations in humans. Previous studies have shown that wild macaques in Thailand have been exposed to the dengue virus. Accordingly, this study aims to characterize the serum proteomic profiles of wild macaques with (seropositive) and without (naive) dengue virus-neutralizing antibodies, to improve our understanding of differential protein expression and identify candidate biomarkers. We analyzed thirty-two serum samples obtained from wild macaques in Thailand. Out of the 32 samples, 16 macaques (50%) were seropositive for DENV. A total of 9,532 proteins were identified, out of which 582 were differentially expressed (DEPs) and used to generate a proteomic profile. Among the nine identified proteins of interest, three were associated with the nervous system, while the remaining six have been reported to play roles in anti-dengue antiviral mechanisms. These include the induction of interferon responses triggered by cellular stress, degradation of viral RNA, and activation of dendritic cells and Th1-mediated immune responses via IFN-\u03b3 and TNF-\u03b1. Although these proteins have been implicated in the nervous system and are involved in anti-DENV in several reports, in this study, it was shown that these proteins remain up-regulated even after infection, which requires further study into the dynamics after long-term infection in the future. These findings highlight the need for further longitudinal studies to validate the functional relevance of these proteins.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0341312","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T18:33:51Z","timestamp":1771871631000},"page":"e0341312","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum proteomic characterization of stump-tailed macaques (Macaca arctoides) with neutralizing antibodies against Dengue virus in Thailand"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4977-9135","authenticated-orcid":true,"given":"Pakorn","family":"Ruengket","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":true,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daraka","family":"Tongthainan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kobporn","family":"Boonnak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanokwan","family":"Taruyanon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bencharong","family":"Sangkharak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6689-2804","authenticated-orcid":true,"given":"Wirasak","family":"Fungfuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"pone.0341312.ref001","doi-asserted-by":"crossref","first-page":"574067","DOI":"10.3389\/fcimb.2021.574067","article-title":"Dengue virus non-structural protein 5 as a versatile, multi-functional effector in host-pathogen interactions","volume":"11","author":"P Bhatnagar","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"pone.0341312.ref002","first-page":"1078","article-title":"Global dengue importation: a systematic review","volume":"21","author":"XWS Gwee","year":"2021","journal-title":"BMC Infect Dis"},{"issue":"7","key":"pone.0341312.ref003","article-title":"Prediction of dengue incidents using hospitalized patients, metrological and socio-economic data in Bangladesh: A machine learning approach","volume":"17","author":"SK Dey","year":"2022","journal-title":"PLoS One"},{"issue":"1","key":"pone.0341312.ref004","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/ajp.22213","article-title":"Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand","volume":"76","author":"K Nakgoi","year":"2014","journal-title":"Am J Primatol"},{"key":"pone.0341312.ref005","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.virusres.2007.10.012","article-title":"Phylogenetic analysis of the NS5 gene of dengue viruses isolated in Ecuador","volume":"132","author":"M Regato","year":"2008","journal-title":"Virus Res"},{"issue":"1","key":"pone.0341312.ref006","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00705-021-05298-2","article-title":"Mammalian animal models for dengue virus infection: a recent overview","volume":"167","author":"MEH Kayesh","year":"2022","journal-title":"Arch Virol"},{"issue":"1","key":"pone.0341312.ref007","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7861\/clinmed.2021-0791","article-title":"Dengue infection: Global importance, immunopathology and management","volume":"22","author":"SA Kularatne","year":"2022","journal-title":"Clin Med (Lond)"},{"issue":"1","key":"pone.0341312.ref008","doi-asserted-by":"crossref","DOI":"10.52225\/narra.v4i1.309","article-title":"Cytokine profiles in dengue fever and dengue hemorrhagic fever: A study from Indonesia","volume":"4","author":"S Masyeni","year":"2024","journal-title":"Narra J"},{"issue":"9","key":"pone.0341312.ref009","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1016\/j.sjbs.2021.05.023","article-title":"Dengue and human health: A global scenario of its occurrence, diagnosis and therapeutics","volume":"28","author":"MJ Sabir","year":"2021","journal-title":"Saudi J Biol Sci"},{"key":"pone.0341312.ref010","volume-title":"Dengue - 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Johansson","year":"2006","journal-title":"Proteomics"},{"issue":"5","key":"pone.0341312.ref035","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/rcm.2898","article-title":"Evaluation of sample fractionation using micro-scale liquid-phase isoelectric focusing on mass spectrometric identification and quantitation of proteins in a SILAC experiment","volume":"21","author":"A Thorsell","year":"2007","journal-title":"Rapid Commun Mass Spectrom"},{"key":"pone.0341312.ref036","volume-title":"Machine learning guide for oil and gas using Python: a step-by-step breakdown with data, algorithms, codes, and applications","author":"HHA Belyadi","year":"2021"},{"key":"pone.0341312.ref037","doi-asserted-by":"crossref","first-page":"26773","DOI":"10.1038\/srep26773","article-title":"Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria","volume":"6","author":"GI Bertin","year":"2016","journal-title":"Sci 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