Rawdata - Tarsal exposure to atovaquone inhibits chikungunya virus transmission by Aedes aegypti mosquitoes, but not the transmission of Zika virus

The antimalarial drug atovaquone was recently reported to inhibit the in vitro replication of different arboviruses, including chikungunya virus (CHIKV) and Zika virus (ZIKV). Furthermore, atovaquone was shown to block Plasmodium parasite transmission by Anopheles mosquitoes when the mosquitoes were exposed to low concentrations on treated surfaces (i.e. tarsal exposure). Therefore, we evaluated the anti-CHIKV and -ZIKV effects of atovaquone via tarsal exposure in Aedes aegypti mosquitoes. We first confirmed that atovaquone exerted a dose-dependent antiviral effect on CHIKV and ZIKV replication in mosquito-derived cells. The modest antiviral effect could be rescued by adding exogenous uridine. Next, we assessed the effect of tarsal exposure to atovaquone on the fitness of Ae. aegypti. Concentrations up to 100 µmol/m² did not affect the fecundity and egg-hatching rate. No significant effect on mosquito survival was observed when mosquitoes were exposed to concentrations up to 25 µmol/m². To evaluate the antiviral effect of atovaquone against CHIKV, we exposed female mosquitoes to 100 µmol/m² atovaquone for 1 h, after which the mosquitoes were immediately infected with CHIKV or ZIKV via bloodmeal. Atovaquone did not significantly reduce ZIKV or CHIKV infection in Ae. aegypti, but successfully blocked the transmission of CHIKV in saliva. Tarsal exposure to antiviral drugs could therefore be a potential new strategy to reduce virus transmission by mosquitoes.

近期有研究报道，抗疟药阿托喹酮（atovaquone）可在体外抑制包括基孔肯雅病毒（chikungunya virus, CHIKV）与寨卡病毒（Zika virus, ZIKV）在内的多种虫媒病毒的复制。此外，当按蚊经处理表面接触低浓度阿托喹酮（即跗节接触暴露）时，该药物可阻断疟原虫经按蚊的传播。为此，本研究评估了通过跗节接触暴露方式给药的阿托喹酮对埃及伊蚊（Aedes aegypti）的抗基孔肯雅病毒及抗寨卡病毒效应。我们首先验证了阿托喹酮在蚊源细胞中对基孔肯雅病毒与寨卡病毒复制具有剂量依赖性的抗病毒作用，且该温和的抗病毒效应可通过添加外源性尿苷逆转。随后，我们考察了跗节接触暴露阿托喹酮对埃及伊蚊适合度的影响。结果显示，浓度最高达100 µmol/m²的阿托喹酮不会影响埃及伊蚊的繁殖力与卵孵化率；当暴露浓度不超过25 µmol/m²时，未观察到对蚊虫存活率的显著影响。为评估阿托喹酮对基孔肯雅病毒的抗病毒效应，我们将雌性埃及伊蚊以100 µmol/m²的阿托喹酮进行1小时的跗节接触暴露，随后立即通过血餐让蚊虫感染基孔肯雅病毒或寨卡病毒。结果表明，阿托喹酮未显著降低埃及伊蚊体内寨卡病毒或基孔肯雅病毒的感染负荷，但成功阻断了基孔肯雅病毒经唾液的传播。综上，跗节接触暴露给药抗病毒药物或可成为降低蚊虫介导病毒传播的新型潜在策略。