期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：48
页码：13863-13868
DOI：10.1073/pnas.1600544113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceUntil it was demonstrated that the Aedes aegypti mosquito transmitted yellow fever, the disease was possibly the most feared pestilence in the western hemisphere. This finding, by Walter Reeds Yellow Fever Commission, is credited with eradication of the disease in many areas, through sanitation programs designed to eliminate the vector. Since this discovery, the mosquito has been widely believed to be complicit in the transmission of viral diseases, earning the enmity of humans everywhere. However, we show here that yellow fever virus encodes a protein that blocks the mosquitos immune response, suggesting the pathogens continued existence in nature depends on staying one step ahead of the vectors antiviral defense. Mosquito-borne flaviviruses, including yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), profoundly affect human health. The successful transmission of these viruses to a human host depends on the pathogens ability to overcome a potentially sterilizing immune response in the vector mosquito. Similar to other invertebrate animals and plants, the mosquitos RNA silencing pathway comprises its primary antiviral defense. Although a diverse range of plant and insect viruses has been found to encode suppressors of RNA silencing, the mechanisms by which flaviviruses antagonize antiviral small RNA pathways in disease vectors are unknown. Here we describe a viral suppressor of RNA silencing (VSR) encoded by the prototype flavivirus, YFV. We show that the YFV capsid (YFC) protein inhibits RNA silencing in the mosquito Aedes aegypti by interfering with Dicer. This VSR activity appears to be broadly conserved in the C proteins of other medically important flaviviruses, including that of ZIKV. These results suggest that a molecular "arms race" between vector and pathogen underlies the continued existence of flaviviruses in nature.
