Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(10), P. 1668 - 1684.e12

Published: Sept. 21, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, roles and contributions of during physiological infection remain unexplored. We assessed role using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. plays key antagonism viral pathogenesis interfering import specifically translocation IRF STAT transcription factors. Additionally, inhibits cellular mRNA export, resulting remodeling cell proteome, regulates protein expression. Interestingly, ORF6:D61L emerged Omicron BA.2 BA.4 variants exhibits reduced Nup98-Rae1 consequently impairs immune evasion. Our findings highlight antagonizing innate immunity emphasize importance studying evasion strategies SARS-CoV-2.

Language: Английский

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Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 617 - 626

Published: July 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Language: Английский

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SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 23, 2023

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial waves were primarily made up sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant mid-2022, several descendants these have since emerged. infections generally caused less disease on average than those by earlier variants concern healthy adult populations, at least, part, due to increased population immunity. Nevertheless, healthcare systems many countries, particularly with low immunity, been overwhelmed unprecedented surges prevalence during waves. Pediatric admissions also higher compared previous concern. All exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against has become challenging a complex background varying coverage, platforms, prior infection rates, hybrid Original messenger RNA booster doses substantially improved VE or BA.2 symptomatic disease. However, protection waned, reductions months after administration. While original CD8 + CD4 T-cell responses cross-recognize sub-lineages, thereby retaining outcomes, variant-adapted vaccines are required expand the breadth B-cell improve durability protection. Variant-adapted rolled out 2022 increase overall antigenically aligned immune mechanisms.

Language: Английский

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SARS-CoV-2 and innate immunity: the good, the bad, and the “goldilocks”

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 171 - 183

Published: Nov. 20, 2023

Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.

Language: Английский

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Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 451 - 463

Published: Jan. 16, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve globally dominant subvariants. Here we compared their replication cell lines and primary airway cultures measured host responses infection. We discovered that subvariants BA.4 BA.5 have improved suppression innate immunity when earlier BA.1 BA.2. Similarly, more recent (BA.2.75 XBB lineages) also triggered reduced immune activation. This correlated increased expression viral antagonists Orf6 nucleocapsid, reminiscent VOCs Alpha Delta. Increased levels suppressed infection by decreasing IRF3 STAT1 signalling transcription factor phosphorylation nuclear translocation. Our data suggest convergent evolution antagonist a common pathway link subvariant dominance evasion.

Language: Английский

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