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Interferon-induced transmembrane protein 3 (IFITM3) limits lethality of SARS-CoV-2 in mice.
Kenney, Adam D; Zani, Ashley; Kawahara, Jeffrey; Eddy, Adrian C; Wang, Xiao-Liang; Mahesh, K C; Lu, Mijia; Thomas, Jeronay; Kohlmeier, Jacob E; Suthar, Mehul S; Hemann, Emily A; Li, Jianrong; Peeples, Mark E; Hall-Stoodley, Luanne; Forero, Adriana; Cai, Chuanxi; Ma, Jianjie; Yount, Jacob S.
  • Kenney AD; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
  • Zani A; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Kawahara J; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
  • Eddy AC; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Wang XL; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
  • Mahesh KC; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Lu M; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
  • Thomas J; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Kohlmeier JE; Department of Surgery, The Ohio State University, Columbus, OH, USA.
  • Suthar MS; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Hemann EA; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Li J; Infectious Diseases Institute, The Ohio State University, Columbus, OH, USA.
  • Peeples ME; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
  • Hall-Stoodley L; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
  • Forero A; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
  • Cai C; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
  • Ma J; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
  • Yount JS; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
EMBO Rep ; 24(4): e56660, 2023 04 05.
Article in English | MEDLINE | ID: covidwho-2265979
ABSTRACT
Interferon-induced transmembrane protein 3 (IFITM3) is an antiviral protein that alters cell membranes to block fusion of viruses. Conflicting reports identified opposing effects of IFITM3 on SARS-CoV-2 infection of cells, and its impact on viral pathogenesis in vivo remains unclear. Here, we show that IFITM3 knockout (KO) mice infected with SARS-CoV-2 experience extreme weight loss and lethality compared to mild infection in wild-type (WT) mice. KO mice have higher lung viral titers and increases in inflammatory cytokine levels, immune cell infiltration, and histopathology. Mechanistically, we observe disseminated viral antigen staining throughout the lung and pulmonary vasculature in KO mice, as well as increased heart infection, indicating that IFITM3 constrains dissemination of SARS-CoV-2. Global transcriptomic analysis of infected lungs shows upregulation of gene signatures associated with interferons, inflammation, and angiogenesis in KO versus WT animals, highlighting changes in lung gene expression programs that precede severe lung pathology and fatality. Our results establish IFITM3 KO mice as a new animal model for studying severe SARS-CoV-2 infection and overall demonstrate that IFITM3 is protective in SARS-CoV-2 infections in vivo.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2023 Document Type: Article Affiliation country: Embr.202256660

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2023 Document Type: Article Affiliation country: Embr.202256660