ArticleJournal of virology2013
The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 198 citations in OpenAlex.
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- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Sensing of Ebinur Lake virus by distinct pattern recognition receptors dictates cell-type specific innate immunity and pathogenesis.Journal of virology · 2025Article
- West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.PLoS pathogens · 2025Article
- Comparison of innate immune responses against arboviruses in mammalian hosts and mosquito vectors.hLife · 2025Review
- From Antibodies to Immunity: Assessing Correlates of Flavivirus Protection and Cross-Reactivity.Vaccines · 2025Review
- MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exposure of negative-sense viral RNA in the cytoplasm initiates innate immunity to West Nile virus.Molecular cell · 2025Article
- Innate immune sensing and vaccine strategies against West Nile virus: role of Toll-like receptors and viral evasion mechanisms.Frontiers in microbiology · 2025Review
- Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.Immunological reviews · 2025Review
- Intranasal vaccines adjuvanted with Nexavant demonstrate robust protective efficacy by inducing both mucosal and systemic immunity in a murine model.Frontiers in immunology · 2025Article
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Usutu virus NS4A suppresses the host interferon response by disrupting MAVS signaling.Virus research · 2024Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Virus recognition and response by the innate immune system are critical components of host defense against infection. Activation of cell-intrinsic immunity and optimal priming of adaptive immunity against West Nile virus (WNV), an emerging vector-borne virus, depend on recognition by RIG-I and MDA5, two cytosolic pattern recognition receptors (PRRs) of the RIG-I-like receptor (RLR) protein family that recognize viral RNA and activate defense programs that suppress infection. We evaluated the individual functions of RIG-I and MDA5 both in vitro and in vivo in pathogen recognition and control of WNV. Lack of RIG-I or MDA5 alone results in decreased innate immune signaling and virus control in primary cells in vitro and increased mortality in mice. We also generated RIG-I(-/-) × MDA5(-/-) double-knockout mice and found that a lack of both RLRs results in a complete absence of innate immune gene induction in target cells of WNV infection and a severe pathogenesis during infection in vivo, similar to findings for animals lacking MAVS, the central adaptor molecule for RLR signaling. We also found that RNA products from WNV-infected cells but not incoming virion RNA display at least two distinct pathogen-associated molecular patterns (PAMPs) containing 5' triphosphate and double-stranded RNA that are temporally distributed and sensed by RIG-I and MDA5 during infection. Thus, RIG-I and MDA5 are essential PRRs that recognize distinct PAMPs that accumulate during WNV replication. Collectively, these experiments highlight the necessity and function of multiple related, cytoplasmic host sensors in orchestrating an effective immune response against an acute viral infection.
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