Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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