The West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles.
| Autor: | Huston NC; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511., Tsao LH; Department of Chemistry, Yale University, New Haven, CT 06511., Brackney DE; Department of Entomology, Connecticut Agricultural Experimental Station, New Haven, CT 06511., Pyle AM; Department of Chemistry, Yale University, New Haven, CT 06511.; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511.; HHMI, Chevy Chase, MD 20815. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 16; Vol. 121 (29), pp. e2312080121. Date of Electronic Publication: 2024 Jul 10. |
| DOI: | 10.1073/pnas.2312080121 |
| Abstrakt: | West Nile virus (WNV) is an arthropod-borne, positive-sense RNA virus that poses an increasing global threat due to warming climates and lack of effective therapeutics. Like other enzootic viruses, little is known about how host context affects the structure of the full-length RNA genome. Here, we report a complete secondary structure of the entire WNV genome within infected mammalian and arthropod cell lines. Our analysis affords structural insights into multiple, conserved aspects of flaviviral biology. We show that the WNV genome folds with minimal host dependence, and we prioritize well-folded regions for functional validation using structural homology between hosts as a guide. Using structure-disrupting, antisense locked nucleic acids, we then demonstrate that the WNV genome contains riboregulatory structures with conserved and host-specific functional roles. These results reveal promising RNA drug targets within flaviviral genomes, and they highlight the therapeutic potential of ASO-LNAs as both WNV-specific and pan-flaviviral therapeutic agents. Competing Interests: Competing interests statement:The authors declare no competing interest. |
| Databáze: | MEDLINE |
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