The West Nile virus genome harbors essential riboregulatory elements with conserved and host- specific functional roles

• 成果类型: Article
• 署名作者: Huston, Nicholas C.; Tsao, Lucille H.; Brackney, Doug E.; Pyle, Anna Marie
• 署名单位: Yale University; Yale University; Connecticut Agricultural Experiment Station; Yale University; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9758
• DOI: 10.1073/pnas.2312080121
• 发表日期: 2024-07-16
• 关键词: selective 2'-hydroxyl acylation; dengue virus; primer extension; rna; replication; translation; mosquito; region; shape; identification

摘要

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- LNAs as both WNV-- specific and pan-- flaviviral therapeutic agents.