Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response

Shalamova, Lyudmila; Felgenhauer, Ulrike; Wilhelm, Jochen; Schaubmar, Andreas R.; Büttner, Kathrin; Schoen, Andreas; Widera, Marek; Ciesek, Sandra; Weber, Friedemann

doi:10.1093/pnasnexus/pgac067

Cited by 24 publications

(28 citation statements)

References 20 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initially, analyses of the growth of Omicron BA.1 in African green monkey Vero cells that are known to have defective IFN expression or human cell lines defective in innate immune sensors led to the speculation that Omicron BA.1 may be more sensitive to innate defenses than other virus strains ( Bojkova et al, 2022a , 2022b ). However, in agreement with our data, emerging evidence indicates that Omicron BA.1 is highly resistant against exogenous IFN ( Guo et al, 2022 ; Shalamova et al, 2022 ).…”

Section: Discussionsupporting

confidence: 93%

“…Expanding recent reports primarily using A549 or Calu-3 cell lines ( Guo et al, 2022 ; Shalamova et al, 2022 ) our results in primary lung epithelial cell models for SARS-CoV-2 support the notion that humoral immune escape and effective IFN escape rather than increased replication capacity helped Omicron BA.1 to outcompete the Delta variant.…”

Section: Discussionsupporting

confidence: 84%

“…One hallmark of VOCs, especially the Omicron variant, is their enhanced escape from neutralizing antibodies ( Cao et al, 2022 ; Pastorio et al, 2022 ; Planas et al, 2022 ). However, increased resistance towards innate immune defenses may also play a key role in its success and is currently debated ( Bojkova et al, 2022b ; Shalamova et al, 2022 ). To address this in physiologically relevant settings, we determined the IFN susceptibility of an early SARS-CoV-2 isolate from February 2020 (NL-02-2020) and five VOC isolates, including Omicron BA.1, in three different human lung cell models.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1

et al. 2023

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Indeed, there was no notable difference in Omicron RNA titers at 24 h.p.i in adult versus pediatric NECs. These data may provide preliminary evidence that the Omicron variant, at least to some extent, is able to evade aspects of the pediatric innate immune response, as has previously been demonstrated [ 38 ]. Whether this is sufficient to result in an increased number of pediatric infections during the Omicron wave [ 39 , 40 ], or whether other factors are more important, remains to be determined.…”

Section: Discussionsupporting

confidence: 68%

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Zhu

Chew

et al. 2022

PLoS Biol

View full text Add to dashboard Cite

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air–liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.

show abstract

“…As well as reducing the induction of interferon, the Alpha and Omicron VOCs are more resistant to inhibition by its antiviral effects 126 , 133 – 135 , 141 . This has been best described as being related to spike adaptations which reduce sensitivity to interferon-induced transmembrane (IFITM) restriction factors 76 , 134 , 142 .…”

Section: Innate Immunity and Sars-cov-2 Variantsmentioning

confidence: 99%

SARS-CoV-2 variant biology: immune escape, transmission and fitness

et al. 2023

View full text Add to dashboard Cite

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates of transmission relative to previous variants and were termed ‘variants of concern’ (VOCs). Designated Alpha, Beta, Gamma, Delta and Omicron, the VOCs emerged independently from one another, and in turn each rapidly became dominant, regionally or globally, outcompeting previous variants. The success of each VOC relative to the previously dominant variant was enabled by altered intrinsic functional properties of the virus and, to various degrees, changes to virus antigenicity conferring the ability to evade a primed immune response. The increased virus fitness associated with VOCs is the result of a complex interplay of virus biology in the context of changing human immunity due to both vaccination and prior infection. In this Review, we summarize the literature on the relative transmissibility and antigenicity of SARS-CoV-2 variants, the role of mutations at the furin spike cleavage site and of non-spike proteins, the potential importance of recombination to virus success, and SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity. SARS-CoV-2 shows a complicated relationship among virus antigenicity, transmission and virulence, which has unpredictable implications for the future trajectory and disease burden of COVID-19.

show abstract

Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response

Cited by 24 publications

References 20 publications

Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1

Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

SARS-CoV-2 variant biology: immune escape, transmission and fitness

Contact Info

Product

Resources

About