ArticleFrontiers in immunology2020
Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Genetic reinstatement of RIG-I in chickens reveals insights into avian immune evolution and influenza interaction.Frontiers in immunology · 2025Article
- Pangolin scales as adaptations for innate immunity against pathogens.BMC biology · 2024Article
- Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.Science China. Life sciences · 2024Article
- An RNA-Seq analysis of coronavirus in the skin of the Pangolin.Scientific reports · 2024Article
- IFIH1-mediated post-transcriptional regulation of PTTG1 promotes proliferation and affects PHA-848125 sensitivity and prognosis in oropharyngeal carcinoma.American journal of cancer research · 2024Article
- Preparation for the next pandemic: challenges in strengthening surveillance.Emerging microbes & infections · 2023Article
- SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.PLoS pathogens · 2023Article
- Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease.The Journal of biological chemistry · 2023Review
- Differential Loss of OAS Genes Indicates Diversification of Antiviral Immunity in Mammals.Vaccines · 2023Article
- Animal Models to Test SARS-CoV-2 Vaccines: Which Ones Are in Use and Future Expectations.Pathogens (Basel, Switzerland) · 2022Review
- Article
- Anti-MDA5 dermatomyositis after COVID-19 vaccination: a case-based review.Rheumatology international · 2022Review
- Review
- Resurrection of an ancient inflammatory locus reveals switch to caspase-1 specificity on a caspase-4 scaffold.The Journal of biological chemistry · 2022Article
- NOD2 and reproduction-associated NOD-like receptors have been lost during the evolution of pangolins.Immunogenetics · 2022Article
- From bats to pangolins: new insights into species differences in the structure and function of the immune system.Innate immunity · 2022Review
- Article
- Animal Models of COVID-19 II. Comparative Immunology.ILAR journal · 2021Review
- Revelations About Aging and Disease from Unconventional Vertebrate Model Organisms.Annual review of genetics · 2021Review
- Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19.Free radical biology & medicine · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zoonotic infections are an imminent threat to human health. Pangolins were recently identified as carriers and intermediate hosts of coronaviruses. Previous research has shown that infection with coronaviruses activates an innate immune response upon sensing of viral RNA by interferon-induced with helicase C domain 1 (IFIH1), also known as MDA5. Here, we performed a comparative genomics study of RNA sensor genes in three species of pangolins. DDX58/RIG-I, a sensor of cytoplasmic viral RNA and toll-like receptors (TLR) 3, 7, and 8, which bind RNA in endosomes, are conserved in pangolins. By contrast, IFIH1 a sensor of intracellular double-stranded RNA, has been inactivated by mutations in pangolins. Likewise, Z-DNA-binding protein (ZBP1), which senses both Z-DNA and Z-RNA, has been lost during the evolution of pangolins. These results suggest that the innate immune response to viruses differs significantly between pangolins and other mammals, including humans. We put forward the hypothesis that loss of IFIH1 and ZBP1 provided an evolutionary advantage by reducing inflammation-induced damage to host tissues and thereby contributed to a switch from resistance to tolerance of viral infections in pangolins.
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