W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
PLoS Negl Trop Dis. 2018 Apr 25;12(4):e0006443. doi: 10.1371/journal.pntd.0006443. eCollection 2018 Apr.
Dengue virus (DENV) is the most prevalent and burdensome arbovirus transmitted by Aedes mosquitoes, against which there is only a limited licensed vaccine and no approved drug treatment. A Chromobacterium species, C. sp. Panama, isolated from the midgut of A. aegypti is able to inhibit DENV replication within the mosquito and in vitro. Here we show that C. sp. Panama mediates its anti-DENV activity through secreted factors that are proteinous in nature. The inhibitory effect occurs prior to virus attachment to cells, and is attributed to a factor that destabilizes the virion by promoting the degradation of the viral envelope protein. Bioassay-guided fractionation, coupled with mass spectrometry, allowed for the identification of a C. sp. Panama-secreted neutral protease and an aminopeptidase that are co-expressed and appear to act synergistically to degrade the viral envelope (E) protein and thus prevent viral attachment and subsequent infection of cells. This is the first study characterizing the anti-DENV activity of a common soil and mosquito-associated bacterium, thereby contributing towards understanding how such bacteria may limit disease transmission, and providing new tools for dengue prevention and therapeutics.
登革热病毒（DENV）是由埃及伊蚊传播的最普遍且负担最重的虫媒病毒，目前仅有有限的许可疫苗，且没有批准的药物治疗方法。从埃及伊蚊中分离出的一种噬菌杆菌属（Chromobacterium）物种 C. sp. Panama 能够抑制蚊体内和体外的 DENV 复制。在这里，我们表明 C. sp. Panama 通过分泌的、本质上是蛋白质的因子来介导其抗 DENV 活性。抑制作用发生在病毒附着到细胞之前，归因于一种因子，该因子通过促进病毒包膜蛋白的降解来破坏病毒粒子的稳定性。基于生物测定的分级分离，结合质谱分析，鉴定出一种 C. sp. Panama 分泌的中性蛋白酶和一种氨肽酶，它们共同表达并似乎协同作用以降解病毒包膜（E）蛋白，从而阻止病毒附着和随后的细胞感染。这是首次对一种常见的土壤和蚊子相关细菌的抗 DENV 活性进行特征描述，从而有助于理解此类细菌如何限制疾病传播，并为登革热的预防和治疗提供新的工具。
