Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes

PLoS Pathogens
Prasad N ParadkarPeter J Walker

Abstract

Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knock...Continue Reading

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Citations

Sep 22, 2016·Parasitology Research·Mengmeng TianChangliang Zhu
Apr 12, 2017·Journal of Medical Entomology·Juxin GuoChangliang Zhu
Nov 1, 2017·Archives of Insect Biochemistry and Physiology·Wenyun YeChangliang Zhu
Jun 11, 2017·Virology Journal·Jean-Bernard DucheminPrasad Paradkar
Jan 23, 2019·Frontiers in Cellular and Infection Microbiology·Marine J Petit, Priya S Shah
Feb 21, 2019·Archives of Insect Biochemistry and Physiology·Juxin GuoChangliang Zhu
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Sep 6, 2018·Scientific Reports·Julie GaburroJean-Bernard Duchemin
Jun 7, 2017·Virology Journal·Jean-Bernard Duchemin, Prasad N Paradkar
Jan 22, 2021·Developmental and Comparative Immunology·Samara Rosendo MachadoPascal Miesen
May 1, 2021·Viruses·Erika Hay-McCullough, Juliet Morrison
Apr 14, 2018·Chemical Reviews·Nicholas J BarrowsMariano A Garcia-Blanco

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Datasets Mentioned

BETA
GSE60229

Methods Mentioned

BETA
RNA-Seq
transfection
Gene knock-down
electrophoresis
FCS

Software Mentioned

Ingenuity
FastQC

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