ArticleJournal of virology2006
PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons.
Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
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Who cites it
169 citing papers in PubMed, 236 citations in OpenAlex.
- IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection.PLoS pathogens · 2012Trial
- Spatial dynamics of viral replication drive biphasic lymphoid activation and systemic alphavirus immune responses.PLoS pathogens · 2026Article
- Lost in translation: interferon-stimulated genes targeting flavivirus protein synthesis.Journal of virology · 2026Review
- The Impact of Corticosteroid Therapy on Patients With West Nile Virus: A Retrospective Cohort Study.The Journal of infectious diseases · 2026Article
- PRRSV Nsp11 antagonizes host antiviral immune response by reducing OAS1 and RNase L expressions.BMC veterinary research · 2026Article
- Condensation of human OAS proteins initiates diverse antiviral activities in response to West Nile virus.Genes & development · 2025Article
- Article
- Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus.Journal of virology · 2024Article
- Activation of ATF3 via the Integrated Stress Response Pathway Regulates Innate Immune Response to Restrict Zika Virus.bioRxiv : the preprint server for biology · 2024Article
- The significance of mosquito saliva in arbovirus transmission and pathogenesis in the vertebrate host.One health (Amsterdam, Netherlands) · 2023Article
- Peste Des Petits Ruminants Virus Nucleocapsid Protein Interacts with Protein Kinase R-Activating Protein and Induces Stress Granules To Promote Viral Replication.Journal of virology · 2023Article
- Stress granules: potential therapeutic targets for infectious and inflammatory diseases.Frontiers in immunology · 2023Review
- A Novel Approach of Antiviral Drugs Targeting Viral Genomes.Microorganisms · 2022Review
- Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein.Life sciences · 2022Article
- Antiviral response within different cell types of the CNS.Frontiers in immunology · 2022Review
- Expression and mechanisms of interferon-stimulated genes in viral infection of the central nervous system (CNS) and neurological diseases.Frontiers in immunology · 2022Review
- Shiftless inhibits flavivirus replication in vitro and is neuroprotective in a mouse model of Zika virus pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses.Virulence · 2021Review
- Zika virus employs the host antiviral RNase L protein to support replication factory assembly.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- HEPN RNases - an emerging class of functionally distinct RNA processing and degradation enzymes.Critical reviews in biochemistry and molecular biology · 2021Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
West Nile virus (WNV) is a neurotropic, mosquito-borne flavivirus that can cause lethal meningoencephalitis. Type I interferon (IFN) plays a critical role in controlling WNV replication, spread, and tropism. In this study, we begin to examine the effector mechanisms by which type I IFN inhibits WNV infection. Mice lacking both the interferon-induced, double-stranded-RNA-activated protein kinase (PKR) and the endoribonuclease of the 2',5'-oligoadenylate synthetase-RNase L system (PKR(-/-) x RL(-/-)) were highly susceptible to subcutaneous WNV infection, with a 90% mortality rate compared to the 30% mortality rate observed in congenic wild-type mice. PKR(-/-) x RL(-/-) mice had increased viral loads in their draining lymph nodes, sera, and spleens, which led to early viral entry into the central nervous system (CNS) and higher viral burden in neuronal tissues. Although mice lacking RNase L showed a higher CNS viral burden and an increased mortality, they were less susceptible than the PKR(-/-) x RL(-/-) mice; thus, we also infer an antiviral role for PKR in the control of WNV infection. Notably, a deficiency in both PKR and RNase L resulted in a decreased ability of type I IFN to inhibit WNV in primary macrophages and cortical neurons. In contrast, the peripheral neurons of the superior cervical ganglia of PKR(-/-) x RL(-/-) mice showed no deficiency in the IFN-mediated inhibition of WNV. Our data suggest that PKR and RNase L contribute to IFN-mediated protection in a cell-restricted manner and control WNV infection in peripheral tissues and some neuronal subtypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.