Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes

被引：109

作者：

Chotiwan, Nunya ^{[1
]}

Andre, Barbara G. ^{[1
]}

Sanchez-Vargas, Irma ^{[1
]}

Islam, M. Nurul ^{[1
]}

Grabowskia, Jeffrey M. ^{[2
,3
,7
]}

Hopf-Jannasch, Amber ^{[4
]}

Gough, Erik ^{[5
]}

Nakayasu, Ernesto ^{[4
,8
]}

Blair, Carol D. ^{[1
]}

Belisle, John T. ^{[1
]}

Hill, Catherine A. ^{[3
,6
]}

Kuhn, Richard J. ^{[2
,6
]}

Perera, Rushika ^{[1
]}

机构：

[1] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

[2] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA

[3] Purdue Univ, Dept Entomol, W Lafayette, IN 47907 USA

[4] Purdue Univ, Bindley Biosci Ctr, MPF, W Lafayette, IN 47907 USA

[5] Purdue Univ, Bindley Biosci Ctr, Computat Life Sci Core, W Lafayette, IN 47907 USA

[6] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA

[7] NIAID, NIH, Rocky Mt Labs, Lab Virol,Biol Vector Borne Viruses Sect, Hamilton, MT USA

[8] Pacific Northwest Natl Lab, Div Biol Sci, Richland, WA USA

来源：

PLOS PATHOGENS | 2018年 / 14卷 / 02期

关键词：

YELLOW-FEVER MOSQUITO; INSECT FAT-BODY; MASS-SPECTROMETRY; WEST NILE; 3-DIMENSIONAL ARCHITECTURE; SPHINGOLIPID METABOLISM; QUANTITATIVE-ANALYSIS; MEMBRANE-LIPIDS; AMINO-ACIDS; ACYL-COA;

D O I：

10.1371/journal.ppat.1006853

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several flaviviruses transmitted by this vector, our results highlight biochemical choke points that could be targeted to disrupt transmission of multiple pathogens by these mosquitoes.

引用

页数：35

共 122 条

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