rnai targeting of west nile virus in mosquito midguts promotes virus diversificationrnai针对西尼罗河病毒的蚊子中肠病毒促进多样化.pdfVIP

RNAi Targeting of West Nile Virus in Mosquito Midguts Promotes Virus Diversification 1 2 1 Doug E. Brackney , Jennifer E. Beane , Gregory D. Ebel * 1 Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America, 2 The Pulmonary Center, Boston University Medical Center, Boston, Massachusetts, United States of America Abstract West Nile virus (WNV) exists in nature as a genetically diverse population of competing genomes. This high genetic diversity and concomitant adaptive plasticity has facilitated the rapid adaptation of WNV to North American transmission cycles and contributed to its explosive spread throughout the New World. WNV is maintained in nature in a transmission cycle between mosquitoes and birds, with intrahost genetic diversity highest in mosquitoes. The mechanistic basis for this increase in genetic diversity in mosquitoes is poorly understood. To determine whether the high mutational diversity of WNV in mosquitoes is driven by RNA interference (RNAi), we characterized the RNAi response to WNV in the midguts of orally exposed Culex pipiens quinquefasciatus using high-throughput, massively parallel sequencing and estimated viral genetic diversity. Our data demonstrate that WNV infection in orally exposed vector mosquitoes induces the RNAi pathway and that regions of the WNV genome that are more intensely targeted by RNAi are more likely to contain point mutations compared to weakly targeted regions. These results suggest that, under natural conditions, positive selection of WNV within mosquitoes is stronger in regions highly targeted by the host RNAi response. Further, they provide a mechanistic basis for the relative importance of mosquitoes in driving WNV divers