Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection
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 h...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00939/full |
| _version_ | 1818337922929131520 |
|---|---|
| author | Heinz Fischer Erwin Tschachler Leopold Eckhart |
| author_facet | Heinz Fischer Erwin Tschachler Leopold Eckhart |
| author_sort | Heinz Fischer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:02:55Z |
| format | Article |
| id | doaj.art-035ccfdbe9034562b0100764d246541f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T15:02:55Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-035ccfdbe9034562b0100764d246541f2022-12-21T23:41:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00939547768Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus InfectionHeinz Fischer0Erwin Tschachler1Leopold Eckhart2Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, Vienna, AustriaZoonotic 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.00939/fullzoonosispangolincoronavirusRNA sensorinnate immunityinflammation |
| spellingShingle | Heinz Fischer Erwin Tschachler Leopold Eckhart Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection Frontiers in Immunology zoonosis pangolin coronavirus RNA sensor innate immunity inflammation |
| title | Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection |
| title_full | Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection |
| title_fullStr | Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection |
| title_full_unstemmed | Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection |
| title_short | Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection |
| title_sort | pangolins lack ifih1 mda5 a cytoplasmic rna sensor that initiates innate immune defense upon coronavirus infection |
| topic | zoonosis pangolin coronavirus RNA sensor innate immunity inflammation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00939/full |
| work_keys_str_mv | AT heinzfischer pangolinslackifih1mda5acytoplasmicrnasensorthatinitiatesinnateimmunedefenseuponcoronavirusinfection AT erwintschachler pangolinslackifih1mda5acytoplasmicrnasensorthatinitiatesinnateimmunedefenseuponcoronavirusinfection AT leopoldeckhart pangolinslackifih1mda5acytoplasmicrnasensorthatinitiatesinnateimmunedefenseuponcoronavirusinfection |