Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management

Joubert, D. Albert; Walker, Thomas; Carrington, Lauren B.; Bruyne, Jyotika Taneja De; Kien, Duong Hue T.; Hoang, Nhat Le Thanh; Châu, Nguyễn Văn Vĩnh; Iturbe‐Ormaetxe, Iñaki; Simmons, Cameron P.; O’Neill, Scott L.

doi:10.1371/journal.ppat.1005434

Cited by 198 publications

(229 citation statements)

References 41 publications

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“…Nonnative Wolbachia strains have been reported to be more effective at pathogen inhibition than native Wolbachia strains in the native host. wAlbB restricts DENV dissemination in its native host, A. albopictus (29,39), albeit to a lesser extent than wAlbB restricts DENV in A. aegypti, a nonnative host (27). Consistent with this hypothesis, transinfection of nonnative wMel into A. albopictus or A. aegypti induces a strong antiviral phenotype (17).…”

Section: Discussionmentioning

confidence: 73%

“…While no investigations have pursued wStri, wAlbB has been shown to inhibit DENV, a relative of ZIKV, in Aedes mosquitoes (27). Group B Wolbachia strains have been shown to have an inhibitory effect on DENV growth in A. albopictus (14,24).…”

Section: Resultsmentioning

confidence: 99%

“…This is due to a loss of maternal transmission and density and a reduced ability to induce cytoplasmic compatibility at tropical cyclic temperatures simulated in laboratory experiments (26). As a result, strategies employing alternative Wolbachia strains, which effectively reduce viral titers without large host fitness costs, have been suggested to improve the efforts of a Wolbachia-mediated suppression strategy (27).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…These are w MelPop‐CLA and w Mel from Drosophila (McMeniman et al., 2009; Walker et al., 2011), w AlbB from Ae. albopictus (Xi, Dean, Khoo, & Dobson, 2005), and w Mel w AlbB (Joubert et al., 2016) that is a superinfection of w Mel and w AlbB. Wolbachia ‐mediated pathogen blocking has now been observed for arboviruses such as WNV (Glaser & Meola, 2010), YFV (van den Hurk et al., 2012), DENV (Bian et al., 2010; Frentiu, Robinson, Young, McGraw, & O'Neill, 2010; Moreira et al., 2009; Walker et al., 2011), ZIKV (Aliota, Peinado, Velez, & Osorio, 2016; Dutra et al., 2016), and Chikungunya virus (van den Hurk et al., 2012; Moreira et al., 2009).…”

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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“…Recently, superinfected Ae. aegypti mosquitoes with two Wolbachia strains (wMel and wAlbB) has been produced, which showed less fitness cost on the mosquitoes and higher viral protection as compared to mosquitoes infected only with wMel (Joubert et al, 2016). The exact mechanism with which Wolbachia produces this antiviral effect is still not well understood.…”

Section: Wolbachia-mosquito Interactionsmentioning

confidence: 99%

Exploring the molecular mechanism(s) involved in Wolbachia-Aedes aegypti-dengue virus interactions

Asad¹

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Dengue is one of the most significant health problems that has magnified its impact globally by affecting about 390 million people annually across 110 countries. The causative agent of this life-threating disease is a positive single stranded RNA arbovirus known as dengue virus (DENV), which uses species of Aedes mosquitoes as vectors. To date, there is no effective available vaccine or cure for dengue, and the control options primarily rely on vector control strategies, mostly through the application of pesticides. However, reports of resistance in Aedes mosquitoes against pesticides has limited this option as well. Therefore, there is an urgent need for alternative approaches to control the spread of DENV. One of the novel options involves the use of the endosymbiotic bacterium Wolbachia, that has successfully limited the ability of Aedes aegypti mosquitoes to transmit a number of life-threatening mosquito-borne viruses such as DENV and Zika virus. Despite its effectiveness to inhibit replication of DENV, very little is known about the mechanism(s) that Wolbachia uses to impart this antiviral effect. In this study, we looked into Ae. aegypti host factors that affect DENV replication and their potential manipulations by Wolbachia to find molecular mechanism(s) that Wolbachia utilizes to limit DENV replication. Knock down studies of AeCHD7 confirmed this assumption as it resulted in significant reductions in DENV replication and virion production. In this study, we have identified AeCHD7 as an Ae. aegypti pro-DENV host factor that is downregulated by Wolbachia which may contribute in limiting DENV replication.Vago is an insect-specific secretory protein that has been identified in Culex quinquefasciatus to play an important role in the crosstalk between the mosquito's immune pathways and reduce West Nile virus (WNV) replication. In Chapter 2, by in-silico identification of Vago characteristic SVWC domain and secretory signal, we identified two potential homologs of the Vago protein in Ae. aegypti and looked at their expression pattern in the case of Wolbachia infection to find that AeVago1 is highly induced in Ae. aegypti upon Wolbachia infection.iii However, we found no induction of AeVago1 expression in Ae. aegypti mosquitoes infected with DENV. Further, AeVago1 knockdown studies demonstrated that there was a significant increase in DENV replication in Wolbachia infected cells in AeVago1 deficient cells. However, there was no effect on Wolbachia density in AeVago1 depleted cells. The outcomes of this study suggest that in the presence of Wolbachia the immune gene AeVago1 is induced, which might also contribute towards inhibition of DENV replication.Pelo has been recently reported as a positive regulator of Drosophila C virus (DCV) replication. However, its role in the case of DENV replication has not been elucidated yet. In Chapter 3, we looked into the possible involvement of pelo in the case of Wolbachia-Ae.aegypti-DENV interactions. We found that the pelo protein levels increase during DENV replicat...

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Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management

Cited by 198 publications

References 41 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

Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes

Exploring the molecular mechanism(s) involved in Wolbachia-Aedes aegypti-dengue virus interactions

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