RT Journal Article
SR Electronic
T1 Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201745
DO 10.26508/lsa.202201745
VO 6
IS 6
A1 Rayhane Nchioua
A1 Annika Schundner
A1 Susanne Klute
A1 Lennart Koepke
A1 Maximilian Hirschenberger
A1 Sabrina Noettger
A1 Giorgio Fois
A1 Fabian Zech
A1 Alexander Graf
A1 Stefan Krebs
A1 Peter Braubach
A1 Helmut Blum
A1 Steffen Stenger
A1 Dorota Kmiec
A1 Manfred Frick
A1 Frank Kirchhoff
A1 Konstantin MJ Sparrer
YR 2023
UL https://www.life-science-alliance.org/content/6/6/e202201745.abstract
AB The IFN system constitutes a powerful antiviral defense machinery. Consequently, effective IFN responses protect against severe COVID-19 and exogenous IFNs inhibit SARS-CoV-2 in vitro. However, emerging SARS-CoV-2 variants of concern (VOCs) may have evolved reduced IFN sensitivity. Here, we determined differences in replication and IFN susceptibility of an early SARS-CoV-2 isolate (NL-02-2020) and the Alpha, Beta, Gamma, Delta, and Omicron VOCs in Calu-3 cells, iPSC-derived alveolar type-II cells (iAT2) and air–liquid interface (ALI) cultures of primary human airway epithelial cells. Our data show that Alpha, Beta, and Gamma replicated to similar levels as NL-02-2020. In comparison, Delta consistently yielded higher viral RNA levels, whereas Omicron was attenuated. All viruses were inhibited by type-I, -II, and -III IFNs, albeit to varying extend. Overall, Alpha was slightly less sensitive to IFNs than NL-02-2020, whereas Beta, Gamma, and Delta remained fully sensitive. Strikingly, Omicron BA.1 was least restricted by exogenous IFNs in all cell models. Our results suggest that enhanced innate immune evasion rather than higher replication capacity contributed to the effective spread of Omicron BA.1.