Frontiers in Immunology (Nov 2022)

Intranasal inoculation of IFN-λ resolves SARS-CoV-2 lung infection via the rapid reduction of viral burden and improvement of tissue damage

  • Haeun Shin,
  • Sujin Kim,
  • Ara Jo,
  • Jina Won,
  • Chan Hee Gil,
  • So Yeon Yoon,
  • Hyunkyung Cha,
  • Hyun Jik Kim,
  • Hyun Jik Kim,
  • Hyun Jik Kim

DOI
https://doi.org/10.3389/fimmu.2022.1009424
Journal volume & issue
Vol. 13

Abstract

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IntroductionThe innate immune responses of upper airway could further our understanding toward antiviral strategies against SARS-CoV-2. We characterize the potential of interferon (IFN)-λ as an innate immune inducer for the rapid clearance of SARS-CoV-2 in the lung and the therapeutic efficacy of intranasal inoculation of IFN-λ to resolve acute lung infection.MethodsSyrian golden hamsters were infected with SARS-CoV-2 and the dynamics of SARS-CoV-2 infection depending on IFN-λ inoculation were tested.ResultsSARS-CoV-2-infected Syrian golden hamsters exhibited a significant decrease in body weight and high viral mRNA level at 3 days post-infection (dpi). Although viral replication was reduced completely from 7 dpi, the pathologic findings remained prominent until 14 dpi in the lung of hamsters. The transcription of IFN-λ was significantly induced in response to SARS-CoV-2 infection with the increase of IFN-stimulated genes. Intranasal inoculation of IFN-λ restricted SARS-CoV-2 replication in the lungs of infected completely from 3 dpi with markedly reduction of inflammatory cytokines. The transcriptional phenotypes were altered to the direction of damage repair and tissue remodeling in the lungs of SARS-CoV-2-infected hamsters following intranasal inoculation of IFN-λ, which improved SARS-CoV-2-caused lung damage.ConclusionCollectively, our findings suggest that IFN-λ might be a potent innate immune inducer in the lung and intranasal inoculation of IFN-λ resolves SARS-CoV-2 infection with rapid viral clearance and improvement of lung damage.

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