Cooler Temperatures Destabilize RNA Interference and Increase Susceptibility of Disease Vector Mosquitoes to Viral Infection
Cooler Temperatures Destabilize RNA Interference and Increase Susceptibility of Disease Vector Mosquitoes to Viral Infection
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DOI：
10.1371/journal.pntd.0002239
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发表时间：
2013-05-01
影响因子：
3.8
通讯作者：
Myles, Kevin M.
中科院分区：
文献类型：
--
作者：
Adelman, Zach N.;Anderson, Michelle A. E.;Myles, Kevin M.
背景：全球气候变化对传染病传播动力学的影响是广泛辩论的主题。蚊媒病毒性疾病的传播特别复杂，气候变量直接影响与病媒流行有关的许多参数。虽然有证据表明，较高的温度通常会缩短虫媒病毒（虫媒病毒）的外在潜伏期，但暴露于较低的温度通常会使病媒蚊子的感染率更高。RNA干扰（RNAi）途径是必不可少的蚊子的抗病毒免疫力，然而，很少有实验探讨了温度对RNAi machinery.Methodology/主要发现的影响：我们利用转基因“传感器”的埃及伊蚊菌株检查RNA沉默的温度的作用。这些“传感器”菌株仅在RNAi被抑制时表达EGFP;例如，在敲低效应蛋白Dicer-2（DCR-2）或Argonaute-2（AGO-2）之后。我们观察到，与28 ℃相比，在18 ℃饲养的转基因传感器蚊子中EGFP表达增加。表达的变化取决于与EGFP序列的一部分同源的反向重复序列的存在，因为缺乏该序列的转基因菌株，RNAi的双链RNA（dsRNA）触发剂，在18 ℃下饲养时，EGFP表达没有变化。对低温下饲养的传感器蚊子中的小RNA进行测序，揭示了dsRNA底物的正常加工，表明观察到的RNAi缺陷发生在DCR-2的下游。饲养在较低的温度也易使蚊子感染基孔肯雅热和黄热病viruses.Conclusions/Significance的更高水平：这些数据表明，小气候，如那些存在于蚊子繁殖场所，以及更一般的气候变量可能会影响蚊子传播的病毒性疾病的动态，通过影响疾病媒介的抗病毒免疫力。
Background: The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference (RNAi) pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery.Methodology/Principal Findings: We utilized transgenic "sensor'' strains of Aedes aegypti to examine the role of temperature on RNA silencing. These "sensor'' strains express EGFP only when RNAi is inhibited; for example, after knockdown of the effector proteins Dicer-2 (DCR-2) or Argonaute-2 (AGO-2). We observed an increase in EGFP expression in transgenic sensor mosquitoes reared at 18 degrees C as compared with 28 degrees C. Changes in expression were dependent on the presence of an inverted repeat with homology to a portion of the EGFP sequence, as transgenic strains lacking this sequence, the double stranded RNA (dsRNA) trigger for RNAi, showed no change in EGFP expression when reared at 18 degrees C. Sequencing small RNAs in sensor mosquitoes reared at low temperature revealed normal processing of dsRNA substrates, suggesting the observed deficiency in RNAi occurs downstream of DCR-2. Rearing at cooler temperatures also predisposed mosquitoes to higher levels of infection with both chikungunya and yellow fever viruses.Conclusions/Significance: This data suggest that microclimates, such as those present in mosquito breeding sites, as well as more general climactic variables may influence the dynamics of mosquito-borne viral diseases by affecting the antiviral immunity of disease vectors.