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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Alphavirus-derived Small Rnas Modulate Pathogenesis In Disease Vector Mosquitoes
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Alphavirus-derived Small Rnas Modulate Pathogenesis In Disease Vector Mosquitoes

机译：甲病毒衍生的小鼻腔调节病媒蚊子的发病机理。

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摘要

Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.
机译：蚊媒病毒在人类和家养动物中引起很高的发病率和死亡率。在自然界中维持蚊媒病毒需要一个生物传播周期，该周期涉及病毒在易感脊椎动物和蚊子宿主中交替复制。尽管脊椎动物感染是急性感染，通常与疾病有关，但这些病毒在自然界的持续传播取决于在蚊媒中建立持续的，非致病性的感染。已经显示出抗病毒RNAi反应会限制果蝇中RNA病毒的复制。但是，尚不清楚RNAi途径作为哺乳动物抗病毒防御的重要性。哺乳动物和蚊子的免疫反应差异可能解释了为什么这些病毒通常与无脊椎动物宿主的病理学无关。我们在感染了蚊媒病毒辛德比斯（SINV）的埃及伊蚊中鉴定出了病毒来源的小干扰RNA（viRNA），其长度为21 nt。 viRNA具有跨越SINV基因组长度的不对称分布。为了确定viRNA在控制致病潜力中的作用，蚊子被表达RNA沉默抑制子的重组α病毒感染。在蚊子中观察到存活率降低，其中抑制了viRNA的积累。这些结果表明，外源性siRNA途径对于被甲病毒感染的蚊子的生存至关重要，因此对于自然界中这些病毒的维持也至关重要。

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