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

Nature Microbiology, Год журнала: 2024, Номер 9(2), С. 451 - 463

Опубликована: Янв. 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.

Язык: Английский

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The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis

The Journal of Cell Biology, Год журнала: 2023, Номер 222(10)

Опубликована: Авг. 8, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses high amounts of the protein Orf9b to target mitochondrial outer membrane Tom70. Tom70 serves as an import receptor for precursors and, independently this function, is critical cellular antiviral response. Previous studies suggested that interferes with Tom70-mediated signaling, but its implication biogenesis unknown. In study, we expressed in human HEK293 cells and observed Orf9b-mediated depletion proteins, particularly respiring cells. To exclude was caused by response, generated a yeast system which function could be recapitulated. Upon expression these cells, again specific decline subset proteins general reduction volume. Thus, SARS-CoV-2 virus able modulate proteome direct effect on Tom70-dependent import.

Язык: Английский

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SARS-CoV-2 evolution during prolonged infection in immunocompromised patients

mBio, Год журнала: 2024, Номер 15(3)

Опубликована: Фев. 16, 2024

ABSTRACT Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate pathways we carried out a study on five experiencing prolonged SARS-CoV-2 (quantitative polymerase chain reaction-positive 79–203 days) who were due treatment lymphoma or solid organ transplantation. For each timepoint analyzed, generated at least two independent genome sequences assess heterogeneity and control sequencing error. Four likely had infection; fifth apparently experienced reinfection. The rates accumulation substitutions per day higher hospitalized than those estimated community background. spike coding region accumulated significantly greater number unique mutations other regions, mutation density was higher. Two treated monoclonal antibodies (bebtelovimab sotrovimab); by next sampled timepoint, virus population showed associated antibody resistance as dominant forms ( K444N E340D). All received remdesivir, but remdesivir-resistant not detected. These data thus help elucidate trends emergence, selection mutational variants within long-term infected individuals. IMPORTANCE is responsible global pandemic, driven part emergence Where do these come from? One model that persistence individuals allows evolution response host pressures, resulting viruses more replicate efficiently humans. In this study, characterize replication several individuals, documenting efficient evolution.

Язык: Английский

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Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses

Cell, Год журнала: 2024, Номер 187(10), С. 2393 - 2410.e14

Опубликована: Апрель 22, 2024

Язык: Английский

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Chasing SARS-CoV-2 XBB.1.16 Recombinant Lineage in India and the Clinical Profile of XBB.1.16 Cases in Maharashtra, India

Cureus, Год журнала: 2023, Номер unknown

Опубликована: Июнь 1, 2023

Background SARS-CoV-2 has evolved rapidly, resulting in the emergence of lineages with a competitive advantage over one another. Co-infections different can give rise to recombinant lineages. To date, XBB lineage is most widespread worldwide, recently named XBB.1.16 causing surge number COVID-19 cases India. Methodology The present study involved retrieval genome sequences from India (between December 1, 2022 and April 8, 2023) through GISAID; were curated, followed by phylogenetic analysis. Demographic clinical data Maharashtra, collected telephonically, recorded Microsoft® Excel, analyzed using IBM® SPSS statistics, version 29.0.0.0 (241). Results A total 2,944 downloaded GISAID database, which 2,856 included following curation. dominated XBB.1.16* (36.17%) XBB.2.3* (12.11%) XBB.1.5* (10.36%). Of cases, 693 Maharashtra; 386 these study. features infection (XBB.1.16* 276 number) showed that 92% those had symptomatic disease, fever (67%), cough (42%), rhinorrhea (33.7%), body ache (14.5%) fatigue (14.1%) being common symptoms. presence comorbidity was found 17.7% cases. Among 91.7% vaccinated at least dose vaccine against COVID-19. While 74.3% home-isolated; 25.7% needed hospitalization/institutional quarantine, these, 33.8% oxygen therapy. Out seven (2.5%) succumbed disease. majority who died belonged an elderly age group (60 years above), underlying comorbid condition/s, supplemental infected other co-circulating Omicron variants similar Conclusion reveals become predominant also shows outcome

Язык: Английский

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Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 17, 2023

Correlates of protection (CoP) are biological parameters that predict a certain level against an infectious disease. Well-established correlates facilitate the development and licensing vaccines by assessing protective efficacy without need to expose clinical trial participants agent which vaccine aims protect. Despite fact viruses have many features in common, can vary considerably amongst same virus family even depending on infection phase is under consideration. Moreover, complex interplay between various immune cell populations interact during high degree genetic variation pathogens, renders identification difficult. Some emerging re-emerging consequence for public health such as SARS-CoV-2, Nipah (NiV) Ebola (EBOV) especially challenging with regards CoP since these pathogens been shown dysregulate response infection. Whereas, neutralising antibodies polyfunctional T-cell responses correlate levels EBOV NiV, other effector mechanisms immunity play important roles shaping turn might serve alternative protection. This review describes different components adaptive innate system activated NiV infections may contribute clearance. Overall, we highlight signatures associated humans could be used CoP.

Язык: Английский

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The rapid emergence of multiple sublineages of Omicron (B.1.1.529) variant: Dynamic profiling via molecular phylogenetics and mutational landscape studies

Journal of Infection and Public Health, Год журнала: 2022, Номер 15(11), С. 1234 - 1258

Опубликована: Окт. 13, 2022

The recent Omicron (B.1.1.529) variant poses a significant threat to global health. This has spread worldwide, and several sublineages have rapidly emerged. Study tried analyze the microevolution of this variant.

Язык: Английский

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Immune Evasion of SARS-CoV-2 Omicron Subvariants

Vaccines, Год журнала: 2022, Номер 10(9), С. 1545 - 1545

Опубликована: Сен. 16, 2022

Since the SARS-CoV-2 Omicron variant (B.1.1.529) was declared a of concern (VOC) by WHO on 24 November 2021, it has caused another global surge cases. With extensive mutations in its spike glycoprotein, gained substantial capabilities to evade antiviral immunity provided vaccination, hybrid immunity, or monoclonal antibodies. The subvariants BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 extended this immune evasion capability having additional unique their respective proteins. ongoing wave emergence new leads concerns regarding efficacy current measurements. To have better understanding subvariants, review summarizes reports BA.4, as well molecular basis evasion.

Язык: Английский

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Global Distribution, Dispersal Patterns, and Trend of Several Omicron Subvariants of SARS-CoV-2 across the Globe

Tropical Medicine and Infectious Disease, Год журнала: 2022, Номер 7(11), С. 373 - 373

Опубликована: Ноя. 12, 2022

Our study aims to describe the global distribution and dispersal patterns of SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, BA.5* variants by geographic region. BA.1* increased in November 2021 South Africa, with a similar increase across all continents early December 2021. did not reach 100% dominance continents. The spread first described differed greatly region, contrast which followed expansion, firstly occurring Asia subsequently Europe, Oceania, North America. BA.4* different pattern, where reached high proportions (maximum 60%) only Africa. is currently, Mid-August 2022, dominant strain, reaching almost continent aside Africa show increasing proportions, Asia, Americas, Oceania are following. emergence new depends mostly on their selective advantage, translated as enhanced transmissibility ability invade people existing immunity. Describing these useful better understanding epidemiology VOCs' transmission generating hypotheses about future emerging variants.

Язык: Английский

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Systematic Exploration of SARS-CoV-2 Adaptation to Vero E6, Vero E6/TMPRSS2, and Calu-3 Cells

Genome Biology and Evolution, Год журнала: 2023, Номер 15(4)

Опубликована: Фев. 28, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, and scientists around the world are currently studying virus intensively in order fight against on-going pandemic of virus. To do so, SARS-CoV-2 is typically grown lab generate viral stocks for various kinds experimental investigations. However, accumulating evidence suggests that such viruses often undergo cell culture adaptation. Here, we systematically explored adaptation two variants, namely B.1.36.16 variant AY.30 variant, a sub lineage B.1.617.2 (Delta) propagated three different lines, including Vero E6, E6/TMPRSS2, Calu-3 cells. Our analyses detected numerous potential changes scattering across entire genome, many which could be found naturally circulating isolates. Notable ones included mutations spike glycoprotein's multibasic cleavage site, Omicron-defining H655Y mutation on glycoprotein, as well nucleocapsid protein's linker region, all were E6-specific. also identified deletion non-structural protein 1 membrane glycoprotein Calu-3-specific changes. S848C 3, located papain-like protease domain, was change, lines. results highlight high adaptability, emphasize need deep-sequence cultured samples when used intricate sensitive biological experiments, illustrate power evolutionary study shedding lights landscape.

Язык: Английский

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