Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes

PLoS Pathog. 2022 Jun 9;18(6):e1010552. doi: 10.1371/journal.ppat.1010552. eCollection 2022 Jun.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes*
  • Animals
  • Arboviruses* / genetics
  • Dengue Virus*
  • Humans
  • Lipase
  • Mosquito Vectors
  • Zika Virus Infection*
  • Zika Virus*

Substances

  • Lipase

Grants and funding

This work was funded by grants from the National Key Research and Development Plan of China (2021YFC2300200-4, 2020YFC1200104, 2018YFA0507202, and 2019YFC1200201) (to G.C. and Y.Z.), the Natural Science Foundation of China (81730063, 31825001, 32188101, 82102389 and 81961160737) (to G.C. and Y.Z.), Tsinghua University Spring Breeze Fund (2020Z99CFG017) (to G.C.), the Open Foundation of NHC Key Laboratory of Tropical Disease Control, Hainan Medical University (2021NHCTDCKFKT22013) (to Y.Z.), the Shenzhen San-Ming Project for prevention and research on vector-borne diseases (SZSM201611064) (to G.C.), the Yunnan Chenggong expert workstation (202005AF150034) (to G.C.), G.C. Innovation Team Project of Yunnan Science and Technology Department (202105AE160020) (to G.C.) and the Young Elite Scientists Sponsorship Program (2021QNRC001) (to Y.Z.).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.