Wolbachia Enhances West Nile Virus (WNV) Infection in the Mosquito Culex tarsalis

Dodson, Brittany L.; Hughes, Grant L; Paul, Oluwatobi; Matacchiero, Amy C.; Kramer, Laura D.; Rasgon, Jason L.

doi:10.1371/journal.pntd.0002965

Cited by 175 publications

(163 citation statements)

References 52 publications

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“…wAlbB has been reported to have opposing phenotypes for different viruses in different mosquito hosts (28)(29)(30)(31), making it an interesting Wolbachia strain for study. wStri of the leafhopper Laodelphax striatella has also been established in Aedes albopictus culture (32), making it potentially useful for future vector suppression approaches, yet it has never been studied in the context of arboviruses.…”

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confidence: 99%

Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures

Schultz

Isern

Michael

et al. 2017

J Virol

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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 Wolbachia pipientis wMel is a novel strategy to reduce Aedes mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of wMel, potentially weakening the integration of this strain into a mosquito population relative to that of other Wolbachia strains. Consequently, it is important to investigate additional Wolbachia strains. All Zika virus (ZIKV) suppression studies are limited to the wMel Wolbachia strain. Here we show ZIKV inhibition by two different Wolbachia strains: wAlbB (isolated from Aedes albopictus mosquitoes) and wStri (isolated from the planthopper Laodelphax striatellus) in mosquito cells. Wolbachia strain wStri inhibited ZIKV most effectively. Singlecycle infection experiments showed that ZIKV RNA replication and nonstructural protein 5 translation were reduced below the limits of detection in wStri-containing cells, demonstrating early inhibition of virus replication. ZIKV replication was rescued when Wolbachia was inhibited with a bacteriostatic antibiotic. We observed a partial rescue of ZIKV growth when Wolbachia-infected cells were supplemented with cholesterol-lipid concentrate, suggesting competition for nutrients as one of the possible mechanisms of Wolbachia inhibition of ZIKV. Our data show that wAlbB and wStri infection causes inhibition of ZIKV, making them attractive candidates for further in vitro mechanistic and in vivo studies and future vector-centered approaches to limit ZIKV infection and spread.IMPORTANCE 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 Wolbachia that can populate mosquito cells and inhibit ZIKV replication. Here we show that two different strains of Wolbachia, wAlbB and wStri, 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 Wolbachia. Our findings further the understanding of Wolbachia 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.KEYWORDS Wolbachia, Zika virus, arthropod vectors, vector biology

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confidence: 99%

Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures

Schultz

Isern

Michael

et al. 2017

J Virol

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“…Best known for its ability to invade invertebrate populations via modification of host reproductive systems (4), some Wolbachia-infected insects are protected from viruses and other pathogens (5)(6)(7)(8)(9)(10)(11)(12), while others have enhanced infection (13)(14)(15)(16)(17). Due to this ability to disrupt virus infection, there is an increased interest in employing Wolbachia as a means of biological control of arthropod-transmitted infectious diseases, such as dengue virus (18).…”

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confidence: 99%

Oxidative Stress Correlates with Wolbachia-Mediated Antiviral Protection in Wolbachia-Drosophila Associations

Wong

Brownlie

Johnson

2015

Appl Environ Microbiol

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bWolbachia mediates antiviral protection in insect hosts and is being developed as a potential biocontrol agent to reduce the spread of insect-vectored viruses. Definition of the molecular mechanism that generates protection is important for understanding the tripartite interaction between host insect, Wolbachia, and virus. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with Wolbachia, suggesting that oxidative stress is important for Wolbachia-mediated antiviral protection. However, Wolbachia experimentally introduced into mosquitoes impacts a range of host fitness traits, some of which are unrelated to antiviral protection. To explore whether elevated oxidative stress is associated with antiviral protection in Wolbachia-infected insects, we analyzed oxidative stress of five Wolbachia-infected Drosophila lines. In flies infected with protective Wolbachia strains, hydrogen peroxide concentrations were 1.25-to 2-fold higher than those in paired fly lines cured of Wolbachia infection. In contrast, there was no difference in the hydrogen peroxide concentrations in flies infected with nonprotective Wolbachia strains compared to flies cured of Wolbachia infection. Using a Drosophila mutant that produces increased levels of hydrogen peroxide, we investigated whether flies with high levels of endogenous reactive oxygen species had altered responses to virus infection and found that flies with high levels of endogenous hydrogen peroxide were less susceptible to virusinduced mortality. Taken together, these results suggest that elevated oxidative stress correlates with Wolbachia-mediated antiviral protection in natural Drosophila hosts.T he maternally inherited endosymbiont Wolbachia pipientis is an alphaproteobacterium predicted to infect at least 40% of insect species (1-3). Best known for its ability to invade invertebrate populations via modification of host reproductive systems (4), some Wolbachia-infected insects are protected from viruses and other pathogens (5-12), while others have enhanced infection (13-17). Due to this ability to disrupt virus infection, there is an increased interest in employing Wolbachia as a means of biological control of arthropod-transmitted infectious diseases, such as dengue virus (18). Despite this interest, the mechanisms of Wolbachia antiviral protection remain to be fully elucidated.Several studies have provided insight into Wolbachia-mediated antiviral protection. Wolbachia can mediate broad protection against a range of different RNA viruses in both Drosophila species and mosquitoes (5-12). Wolbachia-infected Drosophila flies are concomitantly protected against two diverse viruses, Drosophila C virus (DCV; Dicistroviridae) and Flock House virus (FHV; Nodaviridae), and the protection is strongly genetically correlated (6,11,12,19). These findings suggest that Wolbachia mediates antiviral protection through a mechanism with broad specificity. Interestingly, Wolbachia infection often interferes with virus accumulation, but examples have...

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“…tarsalis and An. gambiae where the presence of Wolbachia increased the infection rate of WNV and P. berghei , respectively (Dodson et al., 2014; Hughes et al., 2012). In addition, Wolbachia has been observed to increase susceptibility of the DNA virus nucleopolyhedrovirus in the African armyworm, S. exempta (Graham et al., 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Although largely consistent, there are some reports of Wolbachia enhancing rather than preventing pathogen co‐infection including Plasmodium and WNV within Anopheles gambiae and Culex tarsalis , respectively (Dodson et al., 2014; Hughes, Vega‐Rodriguez, Xue, & Rasgon, 2012). In both of these instances, however, the mosquitoes were only transiently infected with Wolbachia via artificial micro‐injection and so may not be representative of insects with germline tissue infections (Joubert & O'Neill, 2017).…”

Section: Introductionmentioning

confidence: 99%

Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes

Amuzu

Tsyganov

Koh

et al. 2018

Ecology and Evolution

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Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect‐specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness. Wolbachia is an endosymbiotic bacterium of insects that when present in mosquitoes limits the replication of co‐infecting pathogens, including flaviviruses. Artificially created Wolbachia‐infected Aedes aegypti mosquitoes are being released into the wild in a series of trials around the globe with the hope of interrupting dengue and Zika virus transmission from mosquitoes to humans. Our work investigated the effect of Wolbachia on ISF infection in wild‐caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia‐infected mosquitoes compared to the Wolbachia‐free mosquitoes. Our findings demonstrate that the symbiont is capable of manipulating the mosquito virome and that Wolbachia‐mediated viral inhibition is not universal for flaviviruses. This may have implications for the Wolbachia‐based DENV control strategy if ISFs confer fitness effects or alter mosquito susceptibility to other flaviviruses.

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Wolbachia Enhances West Nile Virus (WNV) Infection in the Mosquito Culex tarsalis

Cited by 175 publications

References 52 publications

Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures

Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures

Oxidative Stress Correlates with Wolbachia-Mediated Antiviral Protection in Wolbachia-Drosophila Associations

Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes

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