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SARS-CoV-2 is sensitive to type 1 interferon pretreatment

Kumari G. Lokugamage, Adam Hage, Craig Schindewolf, Ricardo Rajsbaum, Vineet D. Menachery

BioRxiv, Posted March 18, 2020.

Summary

Pre-treatment of Vero E6 cells with IFNa attenuates the replication of a novel SARS-CoV-2 virus but not that of SARS-CoV. SARS-Cov2 is less able to antagonize type I IFN effector functions (STAT1 activation and several ISG induction) compared to a more pathogenic SARS-CoV strain due to sequence changes in ORF3, ORF6 & NSP3, viral genes that inhibit several aspects of type I IFN signalling. Does the study add to current knowledge? Yes Does it challenge existing paradigms? Yes, SARS-CoV was found to be insensitive to IFNa treatment

Research highlights

  1. SARS-CoV2 is sensitive to type I IFN whereas SARS-CoV isn’t
  2. SARS-CoV2 is ineffectively antagonizing IFN-I induced STAT1 phosphorylation and induction of several interferon stimulated genes, such as IFIT2 and TRIM25 in IFN-I pre-treated VERO cells
  3. Big sequences changes in ORF3, ORF6, NSP3 between SARS-CoV & SARS-CoV2 are likely responsible for reduced antagonism of IFN-I effector functions displayed by SARS-CoV2

Research Impact

For serological detection of SARS-COV-2: No

For inhibition of COVID19 transmission: Yes

For treatment of SARS-COV-2 positive individuals: Yes

Methodology

  • Viral sequence comparisons
  • Vero cell infections with virus & viral titer determination
  • Biochemical analysis of anti-viral molecules by immunoblotting after stimulation with SARS-CoV or SARS-CoV2 +/- IFNb

Strengths and weaknesses of the paper

Novelty: Type I IFN establishes an effective anti-viral signalling in SARS-CoV2 infected cells due to sequence changes in several viral genes responsible for antagonizing IFN-I effector functions compared to the previous SARS-CoV.

Reproducibility: Easily reproducible in labs working on viruses as only Vero E6 cells and virus are needed

Appropriate statistics Yes, two-tailed student t-test for comparing infected vs. non-infected

Using model coronavirus and not SARS-COV-2: No, Apart from considering whether the virus is appropriate, one should bear in mind that the appropriateness of the model host is also important; This study has used monkey kidney epithelial cell line despite the wide availability of several human lung epithelial cell lines. In contrast to alveolar epithelium, these cells cannot produce type I interferon so the present study was only able to examine the effector functions of exogenous type I IFN in infected cells. Also, this experimental setup does not allow for the examination of viral antagonism to IFN induction.

Findings easily translated: Yes & No, recombinant IFNa or IFNb treatment could be tested in animal models/ humans as a treatment option