Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
PLoS Pathog. 2022 Jun 9;18(6):e1010552. doi: 10.1371/journal.ppat.1010552. eCollection 2022 Jun.
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.
虫媒病毒是引发各种人类严重疾病的病原体,给全球公共卫生和经济带来了巨大负担;更糟糕的是,大多数虫媒病毒缺乏有效的预防和治疗方法。在此,我们鉴定了一种从埃及伊蚊中分离得到的噬菌 Chromobacterium 细菌分泌的 2 种细菌脂肪酶,Chromobacterium antiviral effector-1 (CbAE-1) 和 CbAE-2,它们对蚊媒病毒具有广谱的抗病毒活性,如登革热病毒 (DENV)、寨卡病毒 (ZIKV)、日本脑炎病毒 (JEV)、黄热病病毒 (YFV) 和辛德毕斯病毒 (SINV)。CbAEs 通过其脂肪酶活性在细胞外环境中有效阻断病毒感染。机制研究表明,这种脂肪酶活性直接破坏了病毒包膜结构,从而使病毒失去感染力。CbAE-1 中脂肪酶基序的突变完全消除了其抗病毒能力。此外,CbAEs 对蚊子还具有脂肪酶依赖性的昆虫病原活性。CbAEs 的抗虫媒病毒和昆虫病原特性使其成为开发针对蚊媒传染病新型传播控制策略的潜在候选药物。