Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV
SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. In this report, we evaluate type-I interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, while SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures (HAEC), we observe the absence of IFN-I stimulation by SARS-CoV-2 alone, but detect failure to counteract STAT1 phosphorylation upon IFN-I pretreatment resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment post infection and found SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame (ORF) 3b and changes to ORF6 suggest the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development.
Errataetall: | |
---|---|
Medienart: |
E-Artikel |
Erscheinungsjahr: |
2020 |
---|---|
Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
---|---|
Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 13. Juli |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Lokugamage, Kumari G [VerfasserIn] |
---|
Links: |
---|
Themen: |
2019-nCoV |
---|
Anmerkungen: |
Date Revised 14.01.2022 published: Electronic UpdateIn: J Virol. 2020 Nov 9;94(23):. - PMID 32938761 Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.1101/2020.03.07.982264 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM310908051 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM310908051 | ||
003 | DE-627 | ||
005 | 20231225141117.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2020 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/2020.03.07.982264 |2 doi | |
028 | 5 | 2 | |a pubmed24n1036.xml |
035 | |a (DE-627)NLM310908051 | ||
035 | |a (NLM)32511335 | ||
035 | |a (PII)2020.03.07.982264 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Lokugamage, Kumari G |e verfasserin |4 aut | |
245 | 1 | 0 | |a Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV |
264 | 1 | |c 2020 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 14.01.2022 | ||
500 | |a published: Electronic | ||
500 | |a UpdateIn: J Virol. 2020 Nov 9;94(23):. - PMID 32938761 | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a SARS-CoV-2, a novel coronavirus (CoV) that causes COVID-19, has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While distinct from SARS-CoV, both group 2B CoVs share similar genome organization, origins to bat CoVs, and an arsenal of immune antagonists. In this report, we evaluate type-I interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication to SARS-CoV, the novel CoV is much more sensitive to IFN-I. In Vero and in Calu3 cells, SARS-CoV-2 is substantially attenuated in the context of IFN-I pretreatment, while SARS-CoV is not. In line with these findings, SARS-CoV-2 fails to counteract phosphorylation of STAT1 and expression of ISG proteins, while SARS-CoV is able to suppress both. Comparing SARS-CoV-2 and influenza A virus in human airway epithelial cultures (HAEC), we observe the absence of IFN-I stimulation by SARS-CoV-2 alone, but detect failure to counteract STAT1 phosphorylation upon IFN-I pretreatment resulting in near ablation of SARS-CoV-2 infection. Next, we evaluated IFN-I treatment post infection and found SARS-CoV-2 was sensitive even after establishing infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonists. The absence of an equivalent open reading frame (ORF) 3b and changes to ORF6 suggest the two key IFN-I antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to IFN-I responses between SARS-CoV and SARS-CoV-2 that may help inform disease progression, treatment options, and animal model development | ||
650 | 4 | |a Preprint | |
650 | 4 | |a 2019-nCoV | |
650 | 4 | |a COVID-19 | |
650 | 4 | |a Coronavirus | |
650 | 4 | |a IFN | |
650 | 4 | |a SARS-CoV | |
650 | 4 | |a SARS-CoV-2 | |
650 | 4 | |a type I interferon | |
700 | 1 | |a Hage, Adam |e verfasserin |4 aut | |
700 | 1 | |a de Vries, Maren |e verfasserin |4 aut | |
700 | 1 | |a Valero-Jimenez, Ana M |e verfasserin |4 aut | |
700 | 1 | |a Schindewolf, Craig |e verfasserin |4 aut | |
700 | 1 | |a Dittmann, Meike |e verfasserin |4 aut | |
700 | 1 | |a Rajsbaum, Ricardo |e verfasserin |4 aut | |
700 | 1 | |a Menachery, Vineet D |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2020) vom: 13. Juli |w (DE-627)NLM31090014X |7 nnns |
773 | 1 | 8 | |g year:2020 |g day:13 |g month:07 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.03.07.982264 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |j 2020 |b 13 |c 07 |