Journal article
Contrasting roles of MERS-CoV and SARS-CoV-2 internal proteins in pathogenesis in mice
mBio, Vol.14(6), e0247623
12/19/2023
DOI: 10.1128/mbio.02476-23
PMCID: PMC10746224
PMID: 37882568
Abstract
Betacoronaviruses encode an internal (I) gene via an alternative reading frame within the nucleocapsid gene, called ORF8b for Middle-East respiratory syndrome coronavirus (MERS-CoV) and ORF9b for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. Previous reports suggested that proteins 8b and 9b are involved in evading multiple innate immune signaling pathways. However, their roles in mediating pathogenesis in infected animals have not been determined. In this study, we abrogated the expression of protein 8b in MERS-CoV and protein 9b in SARS-CoV-2. Using mouse models of MERS-CoV and SARS-CoV-2 infection, we found that MERS-CoV lacking protein 8b expression was more virulent, while SARS-CoV-2 lacking protein 9b expression was attenuated compared with the respective wild-type viruses. Upon further analysis, we detected increased levels of type I interferon and enhanced infiltration of immune cells to the lungs of mice infected with MERS-CoV lacking protein 8b expression. These data suggest that the I protein of MERS-CoV plays a role in limiting pathogenesis while that of SARS-CoV-2 enhances disease severity.
Details
- Title: Subtitle
- Contrasting roles of MERS-CoV and SARS-CoV-2 internal proteins in pathogenesis in mice
- Creators
- Lok-Yin Roy Wong - University of Iowa, Microbiology and ImmunologyAbby Odle - University of Iowa, Microbiology and ImmunologyEmma Luhmann - University of Iowa, Microbiology and ImmunologyDouglas C Wu - University of Illinois Urbana-ChampaignYiquan Wang - University of Illinois Urbana-ChampaignQi Wen Teo - University of Illinois Urbana-ChampaignCeleste Ptak - University of Iowa, Medicine AdministrationAlan Sariol - University of Iowa, Microbiology and ImmunologyShea LoweryMatthias MackDavid K Meyerholz - University of Iowa, PathologyNicholas C Wu - University of Illinois Urbana-ChampaignLilliana Radoshevich - University of Iowa, Molecular Physiology and BiophysicsStanley Perlman - University of Iowa, Iowa Neuroscience Institute
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.14(6), e0247623
- DOI
- 10.1128/mbio.02476-23
- PMID
- 37882568
- PMCID
- PMC10746224
- NLM abbreviation
- mBio
- eISSN
- 2150-7511
- Publisher
- American Society for Microbiology
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: K99 AI170996; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: T32 AI007511; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: P1 AI060699; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI129269; DOI: 10.13039/100000057, name: HHS | NIH | National Institute of General Medical Sciences, award: GM137961; DOI: 10.13039/100014185, name: Searle Scholars Program
- Language
- English
- Electronic publication date
- 10/26/2023
- Date published
- 12/19/2023
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Medicine Administration; Infectious Disease (Pediatrics)
- Record Identifier
- 9984473205502771
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