{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T08:31:13Z","timestamp":1779006673235,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health, National Institute on Aging (NIH\/NIA)","award":["R56AG079190"],"award-info":[{"award-number":["R56AG079190"]}]},{"name":"John S. Dunn Endowment","award":["R56AG079190"],"award-info":[{"award-number":["R56AG079190"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Neurodegenerative diseases are chronic conditions affecting the central nervous system (CNS). Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta in the limbic and cortical brain regions. AD is presumed to result from genetic abnormalities or environmental factors, including viral infections, which may have deleterious, long-term effects. In this study, we demonstrate that the Venezuelan equine encephalitis virus (VEEV) commonly induces neurodegeneration and long-term neurological or cognitive sequelae. Notably, the effects of VEEV infection can persistently influence gene expression in the mouse brain, suggesting a potential link between the observed neurodegenerative outcomes and long-term alterations in gene expression. Additionally, we show that alphavirus encephalitis exacerbates the neuropathological profile of AD through crosstalk between inflammatory and kynurenine pathways, generating a range of metabolites with potent effects. Using a mouse model for \u03b2-amyloidosis, Tg2576 mice, we found that cognitive deficits and brain pathology were more severe in Tg2576 mice infected with VEEV TC-83 compared to mock-infected controls. Thus, during immune activation, the kynurenine pathway plays a more active role in the VEEV TC-83-infected cells, leading to increases in the abundance of transcripts related to the kynurenine pathway of tryptophan metabolism. This pathway generates several metabolites with potent effects on neurotransmitter systems as well as on inflammation, as observed in VEEV TC-83-infected animals.<\/jats:p>","DOI":"10.3390\/pathogens13050397","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T05:16:45Z","timestamp":1715231805000},"page":"397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["VEEV TC-83 Triggers Dysregulation of the Tryptophan\u2013Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-636X","authenticated-orcid":false,"given":"Chanida","family":"Fongsaran","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Neuroinfectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly T.","family":"Dineley","sequence":"additional","affiliation":[{"name":"Neuroinfectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slobodan","family":"Paessler","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Neuroinfectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8965-0979","authenticated-orcid":false,"given":"Irma E.","family":"Cisneros","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Neuroinfectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The alphaviruses: Gene expression, replication, and evolution","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. 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