| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Virus Research, Vol 341, Iss , Pp 199331- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1872-7492 |
| DOI: |
10.1016/j.virusres.2024.199331 |
| Popis: |
Dengue virus infection in humans ranges from asymptomatic infection to severe infection, with ∼2.5 % overall disease fatality rate. Evidence of neurological manifestations is seen in the severe form of the disease, which might be due to the direct invasion of the viruses into the CNS system but is poorly understood. In this study, we demonstrated that the aged AG129 mice are highly susceptible to dengue serotypes 1–4, and following the adaptation, this resulted in the generation of neurovirulent strains that showed enhanced replication, aggravated disease severity, increased neuropathogenesis, and high lethality in both adult and aged AG129 mice. The infected mice had endothelial dysfunction, elicited pro-inflammatory cytokine responses, and exhibited 100 % mortality. Further analysis revealed that aged-adapted DENV strains induced measurable alterations in TLR expression in the aged mice as compared to the adult mice. In addition, metabolomics analysis of the serum samples from the infected adult mice revealed dysregulation of 18 metabolites and upregulation of 6-keto-prostaglandin F1 alpha, phosphocreatine, and taurocholic acid. These metabolites may serve as key biomarkers to decipher and comprehend the severity of dengue-associated severe neuro-pathogenesis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect