Aminopeptidase secreted by Chromobacterium sp. Panama inhibits dengue virus infection by degrading the E protein

• Published in: PLoS neglected tropical diseases 2018-04, Vol.12 (4), p.e0006443-e0006443
• Main Authors: Saraiva, Raúl G, Fang, Jingru, Kang, Seokyoung, Angleró-Rodríguez, Yesseinia I, Dong, Yuemei, Dimopoulos, George
• Format: Article
• Language: English
• Subjects: Aedes; Aedes aegypti; Aminopeptidase; Aminopeptidases; Aminopeptidases - pharmacology; Analysis; Antiviral Agents - pharmacology; Aquatic insects; Bacteria; Bacterial Proteins - pharmacology; Bio-assays; Bioassays; Biodegradation; Biology and Life Sciences; Cells; Chromobacterium; Chromobacterium - enzymology; Culicidae; Degradation; Dengue; Dengue - drug therapy; Dengue - virology; Dengue fever; Dengue virus; Dengue Virus - drug effects; Dengue Virus - physiology; Digestive System - virology; Disease; Disease control; Disease transmission; Fractionation; Human diseases; Immunology; Infections; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Midgut; Mosquitoes; People and places; Proteins; Proteolysis; Public access; Public health; Research and Analysis Methods; Risk factors; Soil; Soil microorganisms; Transmission; Tropical diseases; Vaccines; Vector-borne diseases; Viral diseases; Viral envelope proteins; Viral Envelope Proteins - metabolism; Virion - drug effects; Virions; Virus attachment; Virus Attachment - drug effects; Viruses
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006443

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.