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Interferon-induced transmembrane protein 3 (IFITM3) limits lethality of SARS-CoV-2 in mice

Adam D Kenney1,2, Ashley Zani1,2, Jeffrey Kawahara1,2

  • 1Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.

EMBO Reports
|March 7, 2023
PubMed

Insights

Interferon-induced transmembrane protein 3 (IFITM3) protects against severe SARS-CoV-2 infection. IFITM3 knockout mice showed increased lethality and viral spread, highlighting IFITM3's protective role in vivo.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is an antiviral protein.
  • Previous studies showed conflicting roles for IFITM3 in SARS-CoV-2 infection.
  • The in vivo role of IFITM3 in SARS-CoV-2 pathogenesis was unclear.

Purpose of the Study:

  • To investigate the role of IFITM3 in SARS-CoV-2 infection in vivo.
  • To establish a mouse model for studying severe SARS-CoV-2 infection.

Main Methods:

  • Generation and use of IFITM3 knockout (KO) mice.
  • Infection of wild-type (WT) and KO mice with SARS-CoV-2.
  • Analysis of weight loss, lethality, viral titers, cytokine levels, immune cell infiltration, histopathology, viral antigen distribution, and lung transcriptomics.

Main Results:

  • IFITM3 KO mice exhibited severe weight loss and lethality post-SARS-CoV-2 infection compared to WT mice.
  • KO mice showed higher lung viral loads, increased inflammation, immune cell infiltration, and lung pathology.
  • IFITM3 deficiency led to viral dissemination in the lungs, vasculature, and heart.
  • Transcriptomic analysis revealed upregulated interferon, inflammation, and angiogenesis pathways in KO mice lungs.

Conclusions:

  • IFITM3 constrains SARS-CoV-2 dissemination in vivo.
  • IFITM3 knockout mice serve as a valuable model for severe SARS-CoV-2 infection research.
  • IFITM3 plays a protective role against SARS-CoV-2 pathogenesis.
Keywords:
COVID-19IFITMIFITM3SARS-CoV-2interferon

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