{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:04:47Z","timestamp":1770329087297,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dengue viruses are the causative agents of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, which are mainly transmitted by\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    and\n                    <jats:italic>Aedes albopictus<\/jats:italic>\n                    mosquitoes, and cost billions of dollars annually in patient treatment and mosquito control. Progress in understanding DENV pathogenesis and developing effective treatments has been hampered by the lack of a suitable small pathological animal model. Until now, the candidate vaccine, antibody, and drug for DENV have not been effectively evaluated. Here, we analyzed the pathogenicity of DENV\u20101 in type \u2160 and type \u2161 interferon receptor\u2010deficient mice (AGB6) by intraperitoneal inoculation. Infected mice showed such neurological symptoms as opisthotonus, hunching, ataxia, and paralysis of one or both hind limbs. Viremia can be detected 3 days after infection. It was found that 6.98\u2009\u00d7\u200910\n                    <jats:sup>3<\/jats:sup>\n                    \u2009PFU or higher dose induce 100% mortality. To determine the cause of lethality in mice, heart, liver, spleen, lung, kidney, intestinal, and brain tissues were collected from AGB6 mice (at an attack dose of 6.98\u2009\u00d7\u200910\n                    <jats:sup>3<\/jats:sup>\n                    \u2009PFU) for RNA quantification, and it was found that the viral load in brain tissues peaked at moribund states (14\u2009dpi) and that the viral loads in the other tissues and organs decreased over time. Significant histopathologic changes were observed in brain tissue (hippocampal region and cerebral cortex). Hematological analysis showed hemorrhage and hemoconcentration in infected mice. DENV\u20101 can be isolated from the brain tissue of infected mice. Subsequently, brain tissue transcriptome sequencing was performed to assess host response characteristics in infected AGB6 mice. Transcriptional patterns in brain tissue suggest that aberrant expression of pro\u2010inflammatory cytokines induces antiviral responses and tissue damage. Screening of hub genes and their characterization by qPCR and ELISA, it was hypothesized that IL\u20106 and IFN\u2010\u03b3 might be the key factors in dengue virus\u2010induced inflammatory response. Therefore, this study provides an opportunity to decipher certain aspects of dengue pathogenesis further and provides a new platform for drug, antibody, and vaccine testing.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29895","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T03:42:21Z","timestamp":1725421341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pathogenicity and transcriptomic resolution in dengue virus serotype 1 infected AGB6 mouse model"],"prefix":"10.1002","volume":"96","author":[{"given":"Ning","family":"Yu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Jilin University  Changchun China"},{"name":"Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences  Changchun 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