Journal article

SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon

M Shemesh, TE Aktepe, JM Deerain, JL McAuley, MD Audsley, CT David, DFJ Purcell, V Urin, R Hartmann, GW Moseley, JM Mackenzie, G Schreiber, D Harari

Plos Pathogens | Published : 2021

Open access

Abstract

Type I Interferons (IFN-Is) are a family of cytokines which play a major role in inhibiting viral infection. Resultantly, many viruses have evolved mechanisms in which to evade the IFN-I response. Here we tested the impact of expression of 27 different SARS-CoV-2 genes in relation to their effect on IFN production and activity using three independent experimental methods. We identified six gene products; NSP6, ORF6, ORF7b, NSP1, NSP5 and NSP15, which strongly (>10-fold) blocked MAVS-induced (but not TRIF-induced) IFNβ production. Expression of the first three of these SARS-CoV-2 genes specifically blocked MAVSinduced IFNβ-promoter activity, whereas all six genes induced a collapse in IFNβ mR..

View full abstract

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

We gratefully acknowledge grant support from the following agencies: For the Weizmann Institute, Israel (Schreiber Lab): The Israel Science Foundation (grant No. 3814/19) within the Kill Corona -Curbing Coronavirus Research Program (GS). The Weizmann Institute further acknowledges a grant provided by the Ben B. and Joyce E. Eisenberg Foundation (GS). For The University of Melbourne, Australia: A grant from the Jack Ma Foundation (DFJP) and grants administered by the State Government of Victoria (JMM) to the Mackenzie and to the Purcell Labs. For Monash University, Australia (Moseley Lab): National Health & Medical Research Council, Australia grants: NHMRC Project #1160838 (GWM) and NHMRC Project #1125704 (GWM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.