Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, Virginia, USA.
Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, Virginia, USA.
J Med Virol. 2024 Nov;96(11):e70032. doi: 10.1002/jmv.70032.
Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are emerging/re-emerging alphaviruses transmitted by Aedes spp. mosquitoes and responsible for recent disease outbreaks in the Americas. The capacity of these viruses to cause epidemics is frequently associated with increased mosquito transmission, which in turn is governed by virus-host-vector interactions. Although many studies have explored virus-vector interactions, significant gaps remain in understanding how vertebrate host factors influence alphavirus transmission by mosquitoes. We previously showed that obesity, a ubiquitous vertebrate host biological factor, reduces alphavirus transmission potential in mosquitoes. We hypothesized that alphavirus-infected obese bloodmeals altered immune genes and/or pathways in mosquitoes, thereby inhibiting virus transmission. To test this, we conducted RNA sequencing (RNA-seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) on midgut RNA from mosquitoes fed on alphavirus-infected lean and obese mice. This approach aimed to identify potential antiviral or proviral genes and pathways altered in mosquitoes after consuming infected obese bloodmeals. We found upregulation of the Toll pathway and downregulation of several metabolic and other genes in mosquitoes fed on alphavirus-infected obese bloodmeals. Through gene knockdown studies, we demonstrated the antiviral role of Toll pathway and proviral roles of AAEL009965 and fatty acid synthase (FASN) in the transmission of alphaviruses by mosquitoes. Therefore, this study utilized obesity to identify factors influencing alphavirus transmission by mosquitoes and this research approach may pave the way for designing broadly effective antiviral measures to combat mosquito-borne viruses, such as releasing transgenic mosquitoes deficient in the identified genes.
基孔肯雅病毒（CHIKV）和马亚罗病毒（MAYV）是通过埃及伊蚊传播的新兴/再现的甲病毒，导致美洲最近的疾病爆发。这些病毒引起流行的能力通常与增加的蚊子传播有关，而蚊子传播又受到病毒-宿主-媒介相互作用的控制。尽管许多研究都探讨了病毒-媒介相互作用，但对于脊椎动物宿主因素如何影响蚊子传播甲病毒，仍存在很大的理解差距。我们之前表明，肥胖是一种普遍存在的脊椎动物宿主生物学因素，会降低蚊子传播甲病毒的能力。我们假设感染了病毒的肥胖血液餐改变了蚊子中的免疫基因和/或途径，从而抑制了病毒的传播。为了验证这一点，我们对感染了病毒的肥胖小鼠和瘦小鼠的血液进行了 RNA 测序（RNA-seq）和逆转录定量聚合酶链反应（RT-qPCR），以检测蚊子中受感染的肥胖血液餐改变的潜在抗病毒或促病毒基因和途径。我们发现，在感染了病毒的肥胖血液餐喂养的蚊子中，Toll 途径上调，而几种代谢和其他基因下调。通过基因敲低研究，我们证明了 Toll 途径的抗病毒作用以及 AAEL009965 和脂肪酸合酶（FASN）在蚊子传播甲病毒中的促病毒作用。因此，本研究利用肥胖来鉴定影响蚊子传播甲病毒的因素，这种研究方法可能为设计广泛有效的抗病毒措施来对抗蚊媒病毒铺平道路，例如释放缺乏鉴定基因的转基因蚊子。
