Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 8, 2024

Abstract Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence XBB.1.5, a new Variant Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring S486P spike (S) mutation, subsequent to acquisition nonsense mutation ORF8. Neutralization assays showed similar abilities immune escape between and XBB.1. We determine structural basis for interaction human ACE2 S protein showing overall structures proteins XBB.1.5. provide intrinsic pathogenicity hamsters. Importantly, we find ORF8 impairment MHC suppression. In vivo experiments using recombinant viruses reveal mutations are involved with reduced virulence Together, our study identifies two viral functions defined difference

Язык: Английский

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Characterization of a SARS-CoV-2 EG.5.1 clinical isolate in vitro and in vivo

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113580 - 113580

Опубликована: Дек. 1, 2023

EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that rapidly increasing in prevalence worldwide. However, pathogenicity, transmissibility, and immune evasion properties isolates are largely unknown. Here, we show there no obvious differences growth ability pathogenicity between XBB.1.5 hamsters. We also demonstrate that, like XBB.1.5, transmitted more efficiently hamsters compared to its predecessor, BA.2. In contrast, unlike detect lungs four six exposed hamsters, suggesting virus different from those XBB.1.5. Finally, find neutralizing activity plasma convalescent individuals against was slightly, but significantly, lower than or XBB.1.9.2. Our data suggest after transmission altered antigenicity may be driving over humans.

Язык: Английский

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Virological characteristics of the SARS-CoV-2 XBB.1.5 variant

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 17, 2023

Summary Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence XBB.1.5, a new Variant Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring F486P spike (S) mutation, subsequent to acquisition nonsense mutation ORF8. Neutralization assays showed similar abilities immune escape between and XBB.1. We determined structural basis for interaction human ACE2 S protein showing overall structures proteins XBB.1.5. The intrinsic pathogenicity hamsters is lower than Importantly, we found ORF8 impairment MHC expression. In vivo experiments using recombinant viruses revealed mutations are involved with reduced virulence Together, these data suggest could enhance spreading humans.

Язык: Английский

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

动物学研究, Год журнала: 2024, Номер 45(4), С. 747 - 766

Опубликована: Янв. 1, 2024

The distribution of the immune system throughout body complicates

Язык: Английский

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Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 28, 2025

In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising proteins consisting combinations SARS-CoV-2-derived or peptides antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These are made to increase the immunogenicity and/or enable special targeting immune system. The approach is exemplified solely in a proof concept study by using W-PreS-O, chimeric based single protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 hepatitis B virus (HBV)-derived PreS surface antigen adsorbed aluminum hydroxide. W-PreS-O was evaluated Syrian hamsters which were immunized three times at three-week intervals hydroxide (placebo) before they infected BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, viral loads, as measured RT-PCR upper lower respiratory tracts, determined. addition, infectious titers lungs plaque-forming assay. found that W-PreS-O-vaccinated developed robust nABs against BA.1, showed almost no development pneumonia, had significantly reduced lungs. Importantly, loads nasal cavities close above PCR cycle threshold considered be non-infectious. data our proof-of-concept provides compelling evidence has protective effect hamster vivo infection model thus support promising results obtained also for other

Язык: Английский

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Amino acid substitutions in NSP6 and NSP13 of SARS-CoV-2 contribute to superior virus growth at low temperatures

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

ABSTRACT In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates well at 37°C, which is the temperature of human lower tract, but it poorly 30°C‒32°C, upper tract. The replication efficiency SARS-CoV-2 in tract may directly affect its transmissibility. this study, an XBB.1.5 isolate showed superior replicative ability 32°C and 30°C, whereas most other Omicron sub-variant isolates limited growth. Deep sequencing analysis demonstrated that frequencies viruses possessing NSP6-S163P NSP13-P238S substitutions increased to more than 97% during propagation did not reach 55% 37°C. Reverse genetics revealed these contributed virus growth vitro low temperatures by improving genome replication. Mutant both slightly higher titers hamsters compared parental virus; however, transmissibility between was similar for mutant viruses. Taken together, our findings indicate contribute hamsters. IMPORTANCE Severe efficiently However, airway 30°C–32°C. Therefore, could influence we assessed sub-variants found ability. By deep reverse genetics, amino acid changes NSP6 NSP13 low-temperature growth; improved RNA polymerase activity enhanced Although alone drastically transmissibility, combination with substitutions, they humans. Furthermore, since enhance cultured cells, be used improve production inactivated or live attenuated vaccine virus.

Язык: Английский

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Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters

npj Viruses, Год журнала: 2025, Номер 3(1)

Опубликована: Фев. 24, 2025

Abstract Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529) BA.2 (B.1.1.529.2) viruses. Here, we compared viral replication, pathogenesis, transmissibility these variants. Replication kinetics innate immune response against viruses were tested ex vivo human nasal epithelial cells (HNEC) induced pluripotent stem cell-derived lung organoids (IPSC-LOs), golden hamster model was employed test pathogenicity potential for transmission by respiratory route. Delta, BA.1, replicated more efficiently, outcompeted D614G, Alpha, an HNEC competition assay. viruses, however, poorly IPSC-LOs other Moreover, virus infection significantly increased secretion IFN-λ1, IFN-λ2, IFN-λ3, IL-6, IL-1RA HNECs relative infection, but not IPSC-LOs. The less effectively lungs variants; while reached titers comparable it caused greater pathology. Lastly, transmitted efficiently route efficiently. findings demonstrate ongoing utility experimental risk assessment as continue evolve.

Язык: Английский

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Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4/5, and XBB dominance in Hong Kong: a prospective cohort study

The Lancet Infectious Diseases, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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SARS-CoV-2 Omicron subvariants progressively adapt to human cells with altered host cell entry

mSphere, Год журнала: 2024, Номер 9(9)

Опубликована: Авг. 27, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant exhibits high transmissibility with a strong immune escape ability and causes frequent large-scale global infections by producing predominant subvariants. Here, using human upper/lower airway intestinal cells, we examined the previously dominant BA.1-BA.5 BA.2.75 subvariants, together recently emerged XBB/BQ lineages, in comparison to former Delta variant. We observed tendency for each virus demonstrate higher growth capability than Unlike bronchial nasal epithelial cells accommodated efficient entry of certain similar In contrast Delta's reliance on cell-surface transmembrane protease serine 2, all tested variants depended endosomal cathepsin L. Moreover, S1/S2 cleavage early spikes was less efficient, whereas recent viruses exhibit improved efficacy. Our results show that progressively adapts through continuous endosome-mediated host cell entry.IMPORTANCESARS-CoV-2, causative agent disease 2019, has evolved into number variants/subvariants, which have generated multiple waves infection. order monitor/predict virological features emerging determine appropriate strategies anti-viral development, understanding conserved or altered evolving SARS-CoV-2 is important. this study, addressed subvariants demonstrated gradual adaptation cells. route, from variant, among Collectively, study revealed both changing maintained during evolution.

Язык: Английский

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Omicron breakthrough infections in vaccinated or previously infected hamsters

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(45)

Опубликована: Окт. 30, 2023

The ongoing SARS-CoV-2 epidemic was marked by the repeated emergence and replacement of "variants" with genetic phenotypic distance from ancestral strains, most recent examples being viruses Omicron lineage. Here, we describe a hamster direct contact exposure challenge model to assess protection against reinfection conferred either vaccination or prior infection. We found that two doses self-amplifying RNA vaccine based on Spike ameliorated weight loss following Delta infection decreased viral loads but had minimal effect BA.1 Prior followed breakthrough infections led high degree cross-reactivity all tested variants, suggesting antigenically distinct Spikes, via and/or drives cross-reactive immune response. Alpha variant partially protective infection, whereas animals previously infected exposed became reinfected, although they shed less virus than BA.1-infected naive hamsters. Hamsters reinfected after emitted infectious into air, indicating could be responsible for onwards airborne transmission. further whether protected later sublineages BA.2, BA.4, BA.5. BA.2 not Delta, BA.5 reinfection. These findings suggest cohorts whose only experience COVID-19 is may vulnerable future circulation reemerged Delta-like derivatives, as well emerging sublineages.

Язык: Английский

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