ArticlePLoS pathogens2015
Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- A non-canonical JAK/STAT pathway promotes viral replication through the lipoprotein receptor-related protein in ticks.PLoS biology · 2026Article
- Multiple Transcriptome Analyses Reveal the Selected lncRNA-mRNA and circRNA-mRNA Networks in HepG2 Cells Expressing Genotype 4 Swine Hepatitis E Virus ORF3.Veterinary sciences · 2025Article
- Generation of Cas9 Knock-InDNA · 2025Article
- Ubiquitination of NS1 Confers Differential Adaptation of Zika Virus in Mammalian Hosts and Mosquito Vectors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Sustained antiviral insulin signaling during West Nile virus infection results in viral mutations.Frontiers in cellular and infection microbiology · 2024Article
- Controlling arbovirus infection: high-throughput transcriptome and proteome insights.Frontiers in microbiology · 2024Review
- Wolbachia-mediated resistance to Zika virus infection in Aedes aegypti is dominated by diverse transcriptional regulation and weak evolutionary pressures.PLoS neglected tropical diseases · 2023Article
- Article
- Shift in dominant genotypes of Japanese encephalitis virus and its impact on current vaccination strategies.Frontiers in microbiology · 2023Review
- An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti.Microbiology spectrum · 2022Article
- Human Herpesvirus 6A U4 Inhibits Proteasomal Degradation of the Amyloid Precursor Protein.Journal of virology · 2022Article
- Review
- Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses.PLoS pathogens · 2021Article
- Review
- Alteration in the Culex pipiens transcriptome reveals diverse mechanisms of the mosquito immune system implicated upon Rift Valley fever phlebovirus exposure.PLoS neglected tropical diseases · 2020Article
- Flavivirus Nonstructural Protein NS5 Dysregulates HSP90 to Broadly Inhibit JAK/STAT Signaling.Cells · 2020Article
- Emerging Mechanisms of Insulin-Mediated Antiviral Immunity inFrontiers in immunology · 2019Review
- Dengue virus infection changes Aedes aegypti oviposition olfactory preferences.Scientific reports · 2018Article
- Biochemistry and Molecular Biology of Flaviviruses.Chemical reviews · 2018Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
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 knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication.
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