Type I IFN Signaling Protects Mice from Lethal SARS-CoV-2 Neuroinvasion

Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael McKelvey, Scott C. Weaver, Keer Sun

Research output: Contribution to journalArticlepeer-review


Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable for efficient viral clearance at the adaptive phase of SARS-CoV-2 infection. Conversely, we found that in the absence of IFN-I receptor signaling, the extreme animal lethality is consistent with heightened infectious virus and prominent pathological manifestations in the brain. Taken together, our results in this study demonstrate that IFN-I receptor signaling is required for restricting virus neuroinvasion, thereby mitigating COVID-19 severity.

Original languageEnglish (US)
Pages (from-to)716-721
Number of pages6
Issue number10
StatePublished - Oct 1 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Type I IFN Signaling Protects Mice from Lethal SARS-CoV-2 Neuroinvasion'. Together they form a unique fingerprint.

Cite this