Effect of Wolbachia on Replication of West Nile Virus in a Mosquito Cell Line and Adult Mosquitoes

Abstract

cWolbachia as an endosymbiont is widespread in insects and other arthropods and is best known for reproductive manipulations of the host. Recently, it has been shown that wMelpop and wMel strains of Wolbachia inhibit the replication of several RNA viruses, including dengue virus, and other vector-borne pathogens (e.g., Plasmodium and filarial nematodes) in mosquitoes, providing an alternative approach to limit the transmission of vector-borne pathogens. In this study, we tested the effect of Wolbachia on the replication of West Nile Virus (WNV). Surprisingly, accumulation of the genomic RNA of WNV for all three strains of WNV tested (New York 99, Kunjin, and New South Wales) was enhanced in Wolbachia-infected Aedes aegypti cells (Aag2). However, the amount of secreted virus was significantly reduced in the presence of Wolbachia. Intrathoracic injections showed that replication of WNV in A. aegypti mosquitoes infected with wMel strain of Wolbachia was not inhibited, whereas wMelPop strain of Wolbachia significantly reduced the replication of WNV in mosquitoes. Further, when wMelPop mosquitoes were orally fed with WNV, virus infection, transmission, and dissemination rates were very low in Wolbachia-free mosquitoes and were completely inhibited in the presence of Wolbachia. The results suggest that (i) despite the enhancement of viral genomic RNA replication in the Wolbachia-infected cell line the production of secreted virus was significantly inhibited, (ii) the antiviral effect in intrathoracically infected mosquitoes depends on the strain of Wolbachia, and (iii) replication of the virus in orally fed mosquitoes was completely inhibited in wMelPop strain of Wolbachia.

Wolbachia suppresses cell fusing agent virus in mosquito cells

“…It is worth mentioning that wMelPop strain is known as an over-replicating strain of Wolbachia (McMeniman & O'Neill, 2010;Min & Benzer, 1997) producing a very strong virus blocking effect (Moreira et al, 2009). For example, in our hands, dengue virus was not detectable in aag2.wMelPop-CLA cells infected with the virus when a sensitive method such as RT-qPCR was used (Hussain et al, 2013). While this manuscript was under review, Schnettler et al (2016) also demonstrated that aag2.…”

“…However, some of the major mosquito vectors are devoid of Wolbachia, but when transinfected with Wolbachia from another insect host, virus protection is conferred (Moreira et al, 2009;Xi et al, 2005). For example, in Aedes aegypti mosquitoes stably transinfected with Wobachia, replication of several medically important arboviruses, replication of several medically important arboviruses, such as dengue virus, Zika virus, Chikungunya virus and West Nile virus (WNV), is blocked (Bian et al, 2010;Dutra et al, 2016;Hussain et al, 2013;Moreira et al, 2009). Here, we investigated the effect of Wolbachia on an ISF, cell fusing agent virus (CFAV), in the A. aegypti Aag2 cell line persistently infected with the virus.…”

Mosquito vector‐associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod‐borne diseases

“…In the past decade, studies have shown that certain microbes associated with insect vectors could be used to mediate the transmission of diseases including those transmitted by mosquitoes (Capone et al., 2013; Cirimotich et al., 2011; Dong, Manfredini, & Dimopoulos, 2009; Mourya, Pidiyar, Patole, Gokhale, & Shouche, 2002; Ramirez et al., 2014; Tchioffo et al., 2013; Xi, Ramirez, & Dimopoulos, 2008), tsetse flies (Pais, Lohs, Wu, Wang, & Aksoy, 2008; Wang, Wu, Yang, & Aksoy, 2009; Weiss, Wang, Maltz, Wu, & Aksoy, 2013), sand flies (Sant'Anna et al., 2014), and ticks (Gall et al., 2016; Narasimhan et al., 2014). The most striking example is the inhibition by bacterium Wolbachia pipientis of virus and parasite infection in mosquito vectors (Bian, Xu, Lu, Xie, & Xi, 2010; Blagrove, Arias‐Goeta, Di Genua, Failloux, & Sinkins, 2013; Frentiu et al., 2014; van den Hurk et al., 2012; Hussain et al., 2012; Moreira et al., 2009). Unfortunately, while studies on the application of microbes such as Wolbachia to control human disease have advanced, we still lack basic insight into the natural microbial communities associated with vectors, from viruses to bacteria to single‐celled eukaryotes.…”

Mercadeo Virus: A Novel Mosquito-Specific Flavivirus from Panama

“…The effect of the endosymbiotic bacterium Wolbachia on the vector competence of Aedes aegypti for dengue virus and several other arboviruses has been well documented. [45][46][47] The effect of the midgut microbiota of Ae. aegypti mosquitoes on their vector competence for dengue virus have also been demonstrated.…”