TY - JOUR
T1 - Aminopeptidase secreted by Chromobacterium sp. Panama inhibits dengue virus infection by degrading the E protein
AU - Saraiva, Raúl G.
AU - Fang, Jingru
AU - Kang, Seokyoung
AU - Angleró-Rodríguez, Yesseinia I.
AU - Dong, Yuemei
AU - Dimopoulos, George
N1 - Funding Information:
This work was supported by National Institutes of Health grant R01AI101431, and the Boehringer Ingelheim Fonds (to RGS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank the Johns Hopkins Malaria Research Institute Parasitology core facility.
Publisher Copyright:
© 2018 Saraiva et al.
PY - 2018/4/25
Y1 - 2018/4/25
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pntd.0006443
DO - 10.1371/journal.pntd.0006443
M3 - Article
C2 - 29694346
AN - SCOPUS:85046414202
SN - 1935-2727
VL - 12
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 4
M1 - e0006443
ER -