Jamestown Canyon virus is transmissible by Aedes aegypti and is only moderately blocked by Wolbachia co-infection.
Jamestown Canyon virus is transmissible by Aedes aegypti and is only moderately blocked by Wolbachia co-infection.
复制标题
Jamestown Canyon病毒是由埃及埃及传播的，只有Wolbachia的共同感染将中度阻塞。
DOI：
10.1371/journal.pntd.0011616
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发表时间：
2023-09
影响因子：
3.8
通讯作者：
McGraw, Elizabeth A
中科院分区：
文献类型：
--
作者：
Lau, Meng-Jia;Dutra, Heverton L C;Jones, Matthew J;McNulty, Brianna P;Diaz, Anastacia M;Ware-Gilmore, Fhallon;McGraw, Elizabeth A
詹姆斯敦峡谷峡谷病毒（JCV）是一种负义虫媒病毒，在美国中西部北部越来越常见。通过一系列蚊子属传播，JCV的主要扩增宿主是白尾鹿。埃及伊蚊负责在全球传播各种正义病毒，包括登革热（DENV），寨卡病毒，基孔肯雅病毒和黄热病。AE.埃及的分布范围一度局限于热带地区，但现在正在扩大，部分原因是气候变化。Wolbachia是一种昆虫内共生体，限制了昆虫内共感染病毒的复制。共生体的释放和传播到Ae。埃及人群体在减少DENV向人类的传播方面是有效的，尽管沃尔巴克氏体介导的病毒阻断机制仍然知之甚少。在这里，我们探讨了JCV感染Ae的潜力。埃及伊蚊，载体的免疫反应的性质，以及与沃尔巴克氏体感染的相互作用。我们证明了这一点。埃及伊蚊对JCV具有高度的竞争力，JCV生长到高负荷并在感染性血液餐后迅速到达唾液。蚊子免疫系统以RNAi和JAK/STAT的强烈诱导应答。无论是病毒感染的直接影响，还是对免疫力的积极投入，似乎都不会影响蚊子的寿命。Wolbachia感染仅在感染的早期阶段阻断JCV。与JCV相比，Wolbachia诱导的免疫力很小，这表明先天免疫启动不太可能解释阻断。我们提出了两个模型来解释为什么沃尔巴克氏体对JCV等负义病毒的阻断可能小于正义病毒，这与宿主蛋白质合成的减缓和Vago等干扰素样因子的触发有关。总之，我们强调了人类疾病增加的风险与预测的未来重叠的Ae。埃及和JCV范围。我们认为，与温和的沃尔巴克氏体介导的阻断和独特的生物学，负义病毒代表了一个富有成效的比较模型，以了解其他病毒在蚊子的阻断机制。詹姆斯敦峡谷病毒（Jamestown Canyon virus，JCV）是一种在北美地区新发现的病毒，可通过蚊虫叮咬从野生哺乳动物传播到人类。我们表明，埃及伊蚊，已知的许多病毒病原体传播给人类全球，其分布是向北蔓延，在美国的地区，JCV存在，很可能能够传播病毒。沃尔巴克氏体是一种在野生蚊子种群中释放的内共生细菌，因为它限制了人类病毒在蚊子体内的复制，限制了它们传播给人类。我们表明，沃尔巴克氏体控制JCV复制的能力有限，这可能是因为沃尔巴克氏体诱导的抗病毒反应相当弱，并且负义病毒生物学的独特方面使它们不太容易被阻断。我们的研究结果表明，JCV可以作为一个比较模型，以正义病毒，如登革热在解剖沃尔巴克氏体介导的病毒阻断机制。它还警告说，在气候变化的情况下，蚊子分布的变化可能会使JCV和伊蚊接触更多，从而可能增加人类JCV的发病率。
Jamestown Canyon virus (JCV), a negative-sense arbovirus, is increasingly common in the upper Midwest of the USA. Transmitted by a range of mosquito genera, JCV’s primary amplifying host is white-tailed deer. Aedes aegypti is responsible for transmitting various positive-sense viruses globally including dengue (DENV), Zika, chikungunya, and Yellow Fever. Ae. aegypti’s distribution, once confined to the tropics, is expanding, in part due to climate change. Wolbachia, an insect endosymbiont, limits the replication of co-infecting viruses inside insects. The release and spread of the symbiont into Ae. aegypti populations have been effective in reducing transmission of DENV to humans, although the mechanism of Wolbachia-mediated viral blocking is still poorly understood. Here we explored JCV infection potential in Ae. aegypti, the nature of the vector’s immune response, and interactions with Wolbachia infection. We show that Ae. aegypti is highly competent for JCV, which grows to high loads and rapidly reaches the saliva after an infectious blood meal. The mosquito immune system responds with strong induction of RNAi and JAK/STAT. Neither the direct effect of viral infection nor the energetic investment in immunity appears to affect mosquito longevity. Wolbachia infection blocked JCV only in the early stages of infection. Wolbachia-induced immunity was small compared to that of JCV, suggesting innate immune priming does not likely explain blocking. We propose two models to explain why Wolbachia’s blocking of negative-sense viruses like JCV may be less than that of positive-sense viruses, relating to the slowdown of host protein synthesis and the triggering of interferon-like factors like Vago. In conclusion, we highlight the risk for increased human disease with the predicted future overlap of Ae. aegypti and JCV ranges. We suggest that with moderate Wolbachia-mediated blocking and distinct biology, negative-sense viruses represent a fruitful comparator model to other viruses for understanding blocking mechanisms in mosquitoes. Jamestown Canyon virus (JCV), a newly emerging virus in North America, can result in disease spillover from wild mammals into human populations via the bite of infected mosquitoes. We show that the mosquito Aedes aegypti, known for transmitting many viral pathogens to humans globally, and whose distribution is creeping northward in the USA toward regions where JCV is present, is likely able to transmit the virus. Wolbachia is an endosymbiotic bacterium being released in wild mosquito populations of because it limits the replication of human viruses inside the mosquito, limiting their transmission to humans. We show that Wolbachia has a limited ability to control the replication of JCV, which is likely because Wolbachia-induced antiviral response is quite weak, and unique aspects of negative-sense virus biology make them less susceptible to blocking. Our findings suggest that JCV may serve as a comparative model to positive-sense viruses like dengue in dissecting the mechanism of Wolbachia-mediated virus blocking. It also warns that shifting mosquito distributions, as expected under a changing climate, could bring JCV and Aedes mosquitoes into greater contact, potentially increasing the incidence of JCV in humans.