Year: 2023
Type: article
Abstract: Interferons are a major part of the anti-viral innate defense system. Successful pathogens, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), need to overcome these defenses to establish an infection. Early induction of interferons (IFNs) protects against severe coronavirus disease 2019 (COVID-19). In line with this, SARS-CoV-2 is inhibited by IFNs in vitro , and IFN-based therapies against COVID-19 are investigated in clinical trials. However, SARS-CoV-2 continues to adapt to the human population resulting in the emergence of variants characterized by increased transmission fitness and/or decreased sensitivity to preventive or therapeutic measures. It has been suggested that the efficient spread of these so-called “Variants of Concern” (VOCs) may also involve reduced sensitivity to IFNs. Here, we examined whether the four current VOCs (Alpha, Beta, Gamma and Delta) differ in replication efficiency or IFN sensitivity from an early isolate of SARS-CoV-2. All viruses replicated in a human lung cell line and in iPSC-derived alveolar type II cells (iAT2). The Delta variant showed accelerated replication kinetics and higher infectious virus production compared to the early 2020 isolate. Replication of all SARS-CoV-2 VOCs was reduced in the presence of exogenous type I, II and III IFNs. On average, the Alpha variant was the least susceptible to IFNs and the Alpha, Beta and Gamma variants show increased resistance against type III IFN. Although the Delta variant has outcompeted all other variants in humans it remained as sensitive to IFNs as an early 2020 SARS-CoV-2 isolate. This suggests that increased replication fitness rather than IFN resistance may be a reason for its dominance. Our results may help to understand changes in innate immune susceptibility of VOCs, and inform clinical trials exploring IFN-based COVID-19 therapies.
Source: Life Science Alliance
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,134
Funders: European Commission, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Bundesministerium für Bildung und Forschung, Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg, National Institutes of Health, International Graduate School in Molecular Medicine Ulm, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1085575847, G1195029094, G1262694588, A National iPS Cell Network with Deep Phenotyping for Translational Research, G1636177350, G2109923196, G3504457557, G3637121363, G4353230802, G4774039116, G5068810445, G5189124974, G5243825032, G5514976981, G609277048, G6368729432, SARSCoV2 induzierte Schädigung des Alveolarepithels und dessen Inhibition durch α1antitrypsin., G7294149168, G8076104149, G8320174375, GRK 2203: Mikro und nanoskalige Sensorik für die Lunge
OpenAlex ID: W4361029841