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

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 Wolbachiainfected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbBinfected 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.

Novel phenotype of Wolbachia strain wPip in Aedes aegypti challenges assumptions on mechanisms of Wolbachia-mediated dengue virus inhibition

“…This conclusion is supported by a recent publication from Flores et al . who determined that w Mel inhibits DENV replication in mosquito abdomens better than w AlbB, despite w AlbB residing at higher density than w Mel in the midgut and abdomen as shown here [ 37 ]. Furthermore, it is consistent with reports that w AlbA resides at substantially higher levels than w AlbB and w Mel in the midgut and the salivary glands of Ae .…”

“…Mosquitoes were blood fed on the arms of human volunteers (Monash University human ethics permit CF11/0766-2011000387). The Wolbachia -infected w Mel, w AlbB and w Pip lines as well as matched Tet-control lines ( Wolbachia infected lines that have been cured of their infection by tetracycline treatment) used in these experiments have been described previously [ 15 , 32 , 37 , 56 ]. Tet-control lines were backcrossed to their matched Wolbachia -carrying lines for a minimum of three generations to homogenise their genetic backgrounds.…”

“… DENV-2 (isolated from a patient in Vietnam in 2010) [ 37 ] was injected into the thorax of 7-day old female mosquitoes at 2.4 x10 5 TCID 50 /ml. RNA was extracted from whole mosquito bodies 7-days post infection and virus replication was quantified by qRT-PCR.…”

Large-scale deployment and establishment ofWolbachiainto theAedes aegyptipopulation in Rio de Janeiro, Brazil

“…Wolbachia-harboring Ae. aegypti lines have shown refractoriness to infection by DENV, ZIKV, CHIKV and other medically relevant arboviruses (Moreira et al 2009;Ferguson et al 2015;Dutra et al 2016;Aliota, Peinado, et al 2016;Aliota, Walker, et al 2016;Carrington et al 2018;Flores et al 2020). Levels of refractoriness, nonetheless, seem to vary between strains, with a putative tradeoff with fitness costs (Joubert et al 2016).…”

Comprehensive characterization of internal and cuticle surface microbiota of laboratory-reared F1Anopheles albimanusoriginating from different sites

“…These advances in mosquito microbiota research have led to field applications of mosquito symbionts for mosquito control. For Aedes aegypti, the principal vector of dengue, Zika, chikungunya and yellow fever viruses, mosquitoderived symbionts are now being used to suppress mosquito populations [14] and also being considered to control the spread of pathogens [15]. However, studies exploring mosquito symbionts for malaria control have largely remained at the laboratory stage [16,17].…”