Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes

Author summaryMosquito-borne viruses are the etiological agents of severe human diseases and annually lead to a great number of deaths. These viruses have spread widely and raised major public health concerns throughout the world. Although effective vaccines have been developed for a few mosquito-borne viruses, such as JEV and yellow fever virus (YFV), vaccines or antiviral therapeutics against most mosquito-borne viruses are currently unavailable. In this study, we identified two virucidal and entomopathogenic effectors with lipase activity, CbAE-1 and CbAE-2, from a mosquito midgut derived bacterium Chromobacterium sp. Beijing. Both CbAEs showed potent virucidal activity against a variety of mosquito-borne viruses, including DENV, ZIKV, JEV, YFV, and SINV, as well as other enveloped viruses. Since CbAEs inactivate viruses through their lipase activity by directly disrupting the viral envelope structure, they may provide a novel option for genetically engineering microbiota symbiotic with mosquitoes for arboviral control. Overall, the anti-arboviral and entomopathogenic properties of Csp_BJ and CbAEs render them particularly interesting candidates for the development of novel transmission control strategies against vector-borne diseases. Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.