Aged AG129 mice support the generation of highly virulent novel mouse-adapted DENV (1-4) viruses exhibiting neuropathogenesis and high lethality

• DOI: 10.1016/j.virusres.2024.199331
• Publication Date: 2024-01-31T04:46:31Z
• Authors: Gazala Siddqui; Preeti Vishwakarma; Shikha Saxena; Varun Kumar; Sneh Bajpai; Amit Kumar; Satish Kumar; Ritika Khatri; Jaskaran Kaur; Sankar Bhattacharya; Shubbir Ahmed; Gulam Hussain Syed; Yashwant Kumar; Sweety Samal
• Keywords: Pathogenesis; Lethality

Dengue virus infection in humans ranges from asymptomatic to severe infection, with ∼2.5 % overall disease fatality rate. Evidence of neurological manifestations is seen the form disease, which might be due direct invasion viruses into CNS system but poorly understood. In this study, we demonstrated that aged AG129 mice are highly susceptible dengue serotypes 1-4, and following adaptation, resulted generation neurovirulent strains showed enhanced replication, aggravated severity, increased neuropathogenesis, high lethality both adult mice. The infected had endothelial dysfunction, elicited pro-inflammatory cytokine responses, exhibited 100 mortality. Further analysis revealed aged-adapted DENV induced measurable alterations TLR expression as compared addition, metabolomics serum samples dysregulation 18 metabolites upregulation 6-keto-prostaglandin F1 alpha, phosphocreatine, taurocholic acid. These may serve key biomarkers decipher comprehend severity dengue-associated neuro-pathogenesis.