N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses

MBio
Dan WenAihua Zheng

Abstract

Transmission of flaviviruses by hematophagous insects such as mosquitoes requires acquisition of the virus during blood feeding on the host, with midgut as the primary infection site. Here, we report that N-glycosylation of the E protein, which is conserved among most flaviviruses, is critical for the Zika virus (ZIKV) to invade the vector midgut by inhibiting the reactive oxygen species (ROS) pathway of the mosquito immune system. Our data further show that removal of the ZIKV E glycosylation site prevents mosquito infection by flaviviruses via the oral route, whereas there is no effect on infection by intrathoracic microinjection, which bypasses the midgut. Interestingly, the defect in infection of the mosquito midgut by the mutant virus through blood feeding is rescued by reduction of the ROS level by application of vitamin C, a well-known antioxidant. Therefore, our data demonstrate that ZIKV utilizes the glycosylation on the envelope to antagonize the vector immune defense during infection.IMPORTANCE Most flaviviruses, including Zika virus (ZIKV), are transmitted between hosts by arthropod vectors, such as mosquitoes, which acquire the virus during a blood meal. Here, by mutagenesis, we found a major role of the N-glycosyl...Continue Reading

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Citations

Apr 16, 2019·PLoS Neglected Tropical Diseases·Ju-Mei WangZhen Zou
Aug 15, 2019·PLoS Neglected Tropical Diseases·Lucie DanetNolwenn Jouvenet
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Jun 26, 2021·Current Opinion in Virology·Carlos Daniel Cordero-RiveraRosa María Del Ángel
Jan 18, 2019·Chemosphere·Kenner Morais FernandesGustavo Ferreira Martins

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Datasets Mentioned

BETA
U88535
EF571853
HQ234498
KU527068

Methods Mentioned

BETA
glycosylation
transfection
PCR
Hi-Fi
confocal microscopy

Software Mentioned

ImageJ
Genewiz

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