Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes

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West Nile virus (WNV) is the most geographically widespread arthropod-borne virus (arbovirus) in the world. Like most arboviruses, WNV is a RNA virus which is highly mutable and exists in nature as genetically diverse mutant swarms. Although many recent studies have investigated the relationship between virus mutation rate and viral fitness, this had not previously been determined for WNV or other flaviviruses. We identified WNV mutations associated with variation in mutation rate using cell culture passage in the presence of a mutagen and engineered these mutations into an infectious WNV clone in order to investigate the causes and consequences of altered fidelity. Our results demonstrate that interactions among proteins which comprise the WNV replication complex can significantly alter both the extent and types of mutations that occur. In addition, we show that both increasing and decreasing WNV fidelity has host-specific effects on replication in cell culture and is associated with nearly complete ablation of WNV infection in mosquito vectors. These results have significant implications for our understanding of arbovirus evolution, replication complex function and arboviral fitness in mosquitoes, and identify important targets to study the determinants and mechanisms of vector competence and arbovirus fidelity.

Vyšlo v časopise: Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005009
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005009

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