Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti.

Heather A Flores,Scott L O’Neill,Huynh Thi Thuy Van,Duong Thi Hue Kien,Jyotika Taneja De Bruyne,Vu Tuyet Nhu,Lauren B Carrington,Huynh Thi Le Duyen,Cameron P Simmons,Le Thi Dui,Nguyen Thi Van Thuy,Huynh Thi Xuan Trang,Nguyen Thi Giang,Bridget Wills,Vo Thi Long,Huynh Le Anh Huy,Nguyễn Thanh Phong ,Trần Thi Thúy ,Tanya B O'donnell ,Nguyễn Văn Vĩnh Châu

doi:10.1371/journal.ppat.1008433

Abstract

The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes. All Wolbachia-infected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbB-infected mosquitoes were more susceptible to whole body infection than wMel and wMelCS. We extended these findings via mosquito oral feeding experiments, using viremic blood from 36 acute, hospitalised dengue cases in Vietnam, additionally including wMel and wildtype mosquitoes on a Vietnamese nuclear genetic background. As above, wAlbB was less effective at blocking DENV replication in the abdomen compared to wMel and wMelCS. The transmission potential of all Wolbachia-infected mosquito lines (measured by the presence/absence of infectious DENV in mosquito saliva) after 14 days, was significantly reduced compared to their wildtype counterparts, and lowest for wMelCS and wAlbB. These data support the use of wAlbB and wMelCS strains for introgression field trials and the biocontrol of DENV transmission. Furthermore, despite observing significant differences in transmission potential between wildtype mosquitoes from Australia and Vietnam, no difference was observed between wMel-infected mosquitoes from each background suggesting that Wolbachia may override any underlying variation in DENV transmission potential.

Highlights

Aedes aegypti transmit a number of medically important arboviruses, including dengue, Zika, chikungunya, Mayaro and yellow fever viruses
Using two different methods to measure viral replication and transmission potential, we show that both strains provide improved viral protection over wMel in the lab supporting further examination in field trials
We further compare the transmission potential of wMel in two different genetic backgrounds and find that wMel provides equivalent levels of viral blocking despite differences observed in wildtype mosquitoes, suggesting that viral blocking induced by wMel may override any underlying variation for dengue virus (DENV) transmission potential

Summary

Introduction

Aedes aegypti can transmit a number of medically important arboviruses, including dengue, Zika, chikungunya, Mayaro and yellow fever viruses [1,2,3,4,5]. Together, these viruses cause significant morbidity and mortality across the world, with an estimated 100 million people experiencing a symptomatic dengue virus (DENV) infection each year [6]. WMel has been well-characterised for its capacity to block DENV infection and replication in Ae. aegypti using different challenge methods [1,13,14,15,16,17,18]. WMel almost completely reduces the transmission potential of mosquitoes orally challenged with cultured DENV spiked into animal blood [13,15,16,20]

Results

Discussion

Conclusion