Schultz Michaela J, Isern Sharon, Michael Scott F, Corley Ronald B, Connor John H, Frydman Horacio M
Department of Biology, Boston University, Boston, Massachusetts, USA.
National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA.
J Virol. 2017 Jun 26;91(14). doi: 10.1128/JVI.00339-17. Print 2017 Jul 15.
Mosquito-borne arboviruses are a major source of human disease. One strategy to reduce arbovirus disease is to reduce the mosquito's ability to transmit virus. Mosquito infection with the bacterial endosymbiont Mel is a novel strategy to reduce mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of Mel, potentially weakening the integration of this strain into a mosquito population relative to that of other strains. Consequently, it is important to investigate additional strains. All Zika virus (ZIKV) suppression studies are limited to the Mel strain. Here we show ZIKV inhibition by two different strains: AlbB (isolated from mosquitoes) and Stri (isolated from the planthopper ) in mosquito cells. strain Stri inhibited ZIKV most effectively. Single-cycle infection experiments showed that ZIKV RNA replication and nonstructural protein 5 translation were reduced below the limits of detection in Stri-containing cells, demonstrating early inhibition of virus replication. ZIKV replication was rescued when was inhibited with a bacteriostatic antibiotic. We observed a partial rescue of ZIKV growth when -infected cells were supplemented with cholesterol-lipid concentrate, suggesting competition for nutrients as one of the possible mechanisms of inhibition of ZIKV. Our data show that AlbB and Stri infection causes inhibition of ZIKV, making them attractive candidates for further mechanistic and studies and future vector-centered approaches to limit ZIKV infection and spread. Zika virus (ZIKV) has swiftly spread throughout most of the Western Hemisphere. This is due in large part to its replication in and spread by a mosquito vector host. There is an urgent need for approaches that limit ZIKV replication in mosquitoes. One exciting approach for this is to use a bacterial endosymbiont called that can populate mosquito cells and inhibit ZIKV replication. Here we show that two different strains of , AlbB and Stri, are effective at repressing ZIKV in mosquito cell lines. Repression of virus growth is through the inhibition of an early stage of infection and requires actively replicating Our findings further the understanding of viral inhibition and provide novel tools that can be used in an effort to limit ZIKV replication in the mosquito vector, thereby interrupting the transmission and spread of the virus.
蚊媒虫媒病毒是人类疾病的主要来源。减少虫媒病毒疾病的一种策略是降低蚊子传播病毒的能力。用细菌内共生体Mel感染蚊子是一种降低蚊子感染黄病毒能力的新策略。然而,研究周期性环境温度的实验表明,Mel的母系传播减少,相对于其他菌株,这可能会削弱该菌株融入蚊子种群的能力。因此,研究其他菌株很重要。所有寨卡病毒(ZIKV)抑制研究都仅限于Mel菌株。在这里,我们展示了两种不同菌株(从蚊子中分离出的AlbB和从稻飞虱中分离出的Stri)在蚊子细胞中对ZIKV的抑制作用。Stri菌株对ZIKV的抑制最为有效。单周期感染实验表明,在含有Stri的细胞中,ZIKV RNA复制和非结构蛋白5翻译减少到检测限以下,表明病毒复制受到早期抑制。当用抑菌抗生素抑制时,ZIKV复制得以恢复。当用胆固醇脂质浓缩物补充感染的细胞时,我们观察到ZIKV生长的部分恢复,这表明营养竞争是抑制ZIKV的可能机制之一。我们的数据表明,AlbB和Stri感染会导致ZIKV受到抑制,这使得它们成为进一步进行机制和研究以及未来以载体为中心的限制ZIKV感染和传播方法的有吸引力的候选对象。寨卡病毒(ZIKV)已迅速传播到西半球的大部分地区。这在很大程度上归因于其在蚊媒宿主中的复制和传播。迫切需要限制ZIKV在蚊子中复制的方法。一种令人兴奋的方法是使用一种名为的细菌内共生体,它可以在蚊子细胞中繁殖并抑制ZIKV复制。在这里,我们表明,AlbB和Stri这两种不同的菌株在蚊子细胞系中有效抑制ZIKV。病毒生长的抑制是通过抑制感染的早期阶段实现的,并且需要活跃复制的。我们的发现进一步加深了对病毒抑制的理解,并提供了可用于限制ZIKV在蚊媒中复制的新工具,从而中断病毒的传播和扩散。