Pluripotency of Wolbachia against Arboviruses: the case of yellow fever

Gates Open Res. 2019 Apr 16:3:161. doi: 10.12688/gatesopenres.12903.2. eCollection 2019.

Abstract

Background: Yellow fever outbreaks have re-emerged in Brazil during 2016-18, with mortality rates up to 30%. Although urban transmission has not been reported since 1942, the risk of re-urbanization of yellow fever is significant, as Aedes aegypti is present in most tropical and sub-tropical cities in the World and still remains the main vector of urban YFV. Although the YFV vaccine is safe and effective, it does not always reach populations at greatest risk of infection and there is an acknowledged global shortage of vaccine supply. The introgression of Wolbachia bacteria into Ae. aegypti mosquito populations is being trialed in several countries ( www.worldmosquito.org) as a biocontrol method against dengue, Zika and chikungunya. Here, we studied the ability of Wolbachia to reduce the transmission potential of Ae. aegypti mosquitoes for Yellow fever virus (YFV). Methods: Two recently isolated YFV (primate and human) were used to challenge field-derived wild-type and Wolbachia-infected ( wMel +) Ae. aegypti mosquitoes. The YFV infection status was followed for 7, 14 and 21 days post-oral feeding (dpf). The YFV transmission potential of mosquitoes was evaluated via nano-injection of saliva into uninfected mosquitoes or by inoculation in mice. Results: We found that Wolbachia was able to significantly reduce the prevalence of mosquitoes with YFV infected heads and thoraces for both viral isolates. Furthermore, analyses of mosquito saliva, through indirect injection into naïve mosquitoes or via interferon-deficient mouse model, indicated Wolbachia was associated with profound reduction in the YFV transmission potential of mosquitoes (14dpf). Conclusions: Our results suggest that Wolbachia introgression could be used as a complementary strategy for prevention of urban yellow fever transmission, along with the human vaccination program.

Keywords: Aedes aegypti; Wolbachia; Yellow fever virus; vector competence.

Grants and funding

Bill Melinda Gates Foundation through Monash University and the Brazilian Ministry of Health (DECIT) [OPP1140230]. This work was partially supported by the National Institute of Science and Technology in Dengue and Host-microorganism Interaction (INCT Dengue), and the Minas Gerais Foundation for Science (FAPEMIG, Brazil). LAM and MMT are fellows from CNPq, Brazil. This work also received support from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação Ezequiel Dias (FUNED). LCJA, FCMI and MG have used sequencing primers and protocols from the ZIBRA2 project funded from CNPq and CAPES (440685/2016-8 and 88887.130716/2016-00).