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

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 criti...

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Autores principales:	Dan Wen, Suhua Li, Fangfang Dong, Yanan Zhang, Yongfang Lin, Jumei Wang, Zhen Zou, Aihua Zheng
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	flavivirus glycosylation mosquito transmission Zika Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/68df7d30d5654cb4a353c002b2086176
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spelling	oai:doaj.org-article:68df7d30d5654cb4a353c002b20861762021-11-15T15:53:26ZN-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses10.1128/mBio.00046-182150-7511https://doaj.org/article/68df7d30d5654cb4a353c002b20861762018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00046-18https://doaj.org/toc/2150-7511ABSTRACT 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-glycosylation of flavivirus E protein in its transmission circle, facilitating its survival against the vector immune system during invasion of the mosquito midgut while blood feeding on the host. In spite of the extensive studies of the involvement of N-glycan modification of flavivirus E protein in virus-host interactions, we discovered its critical role in virus-vector interaction and the evolution of flavivirus. Given the deleterious effects of ZIKV on human health, this study might have a significant impact on development of novel transmission-blocking strategies.Dan WenSuhua LiFangfang DongYanan ZhangYongfang LinJumei WangZhen ZouAihua ZhengAmerican Society for MicrobiologyarticleflavivirusglycosylationmosquitotransmissionZikaMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	flavivirus glycosylation mosquito transmission Zika Microbiology QR1-502
spellingShingle	flavivirus glycosylation mosquito transmission Zika Microbiology QR1-502 Dan Wen Suhua Li Fangfang Dong Yanan Zhang Yongfang Lin Jumei Wang Zhen Zou Aihua Zheng N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
description	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-glycosylation of flavivirus E protein in its transmission circle, facilitating its survival against the vector immune system during invasion of the mosquito midgut while blood feeding on the host. In spite of the extensive studies of the involvement of N-glycan modification of flavivirus E protein in virus-host interactions, we discovered its critical role in virus-vector interaction and the evolution of flavivirus. Given the deleterious effects of ZIKV on human health, this study might have a significant impact on development of novel transmission-blocking strategies.
format	article
author	Dan Wen Suhua Li Fangfang Dong Yanan Zhang Yongfang Lin Jumei Wang Zhen Zou Aihua Zheng
author_facet	Dan Wen Suhua Li Fangfang Dong Yanan Zhang Yongfang Lin Jumei Wang Zhen Zou Aihua Zheng
author_sort	Dan Wen
title	N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
title_short	N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
title_full	N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
title_fullStr	N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
title_full_unstemmed	N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses
title_sort	n-glycosylation of viral e protein is the determinant for vector midgut invasion by flaviviruses
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/68df7d30d5654cb4a353c002b2086176
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N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses

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