Exploring immune evasion of SARS-CoV-2 variants using a pseudotyped system DOI Creative Commons
Haixiao Duan,

Ershuai Zhang,

Ge Ren

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(8), P. e29939 - e29939

Published: April 1, 2024

In the United States, coronavirus disease 2019 (COVID-19) cases have consistently been linked to prevailing variant XBB.1.5 of SARS-CoV-2 since late 2022. A system has developed for producing and infecting cells with a pseudovirus (PsV) investigate infection in Biosafety Level 2 (BSL-2) laboratory. This utilizes lentiviral vector carrying ZsGreen1 Firefly luciferase (Fluc) dual reporter genes, facilitating analysis experimental results. addition, we created panel PsV variants that depict both previous presently circulating mutations found strains. series PsVs includes prototype SARS-CoV-2, Delta B.1.617.2, BA.5, XBB.1, XBB.1.5. To facilitate study infections caused by different PsV, HEK-293T cell line expressing mCherry human angiotensin converting enzyme (ACE2). validate whether can be used neutralization assays, employed serum from rats immunized PF-D-Trimer protein vaccine its inhibitory effect on infectivity various variants. According our observations, XBB variant, particularly XBB.1.5, exhibits stronger immune evasion capabilities than BA.5 Hence, utilizing test, this capability forecast effectiveness preventing future infections.

Language: Английский

Virological characteristics of the SARS‐CoV‐2 Omicron EG.5.1 variant DOI Creative Commons
Shuhei Tsujino, Sayaka Deguchi, Tomo Nomai

et al.

Microbiology and Immunology, Journal Year: 2024, Volume and Issue: 68(9), P. 305 - 330

Published: July 4, 2024

Abstract In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron XBB, EG.5.1 (a progeny XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures experimental animals, use human sera antiviral compounds, reveal virological features newly emerging variant. Our analysis modeling suggested that two hallmark substitutions EG.5.1, S:F456L ORF9b:I5T are critical its increased viral fitness. Experimental investigations on growth kinetics, sensitivity clinically available antivirals, fusogenicity, pathogenicity comparable those XBB.1.5. However, cryo‐electron microscopy revealed structural differences between spike proteins further assessed impact features, but it was almost negligible our setup. provide knowledge for understanding evolutionary traits pathogenic viruses, population.

Language: Английский

Citations

15
Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19 DOI Creative Commons
Zhouyi Rong, Hongcheng Mai, Gregor Ebert

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(12), P. 2112 - 2130.e10

Published: Nov. 29, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways neurodegeneration-associated changes. Similar distribution patterns SARS-CoV-2-infected mice. Injection alone was sufficient to induce neuroinflammation, proteome changes axis, anxiety-like behavior, exacerbated outcomes mouse models stroke traumatic injury. Vaccination reduced but did not eliminate Our findings suggest persistent at borders may contribute lasting sequelae COVID-19.

Language: Английский

Citations

10
Severity of SARS-CoV-2 Omicron XBB subvariants in Singapore DOI Creative Commons
Rachael Pung,

Xin Peng Kong,

Lin Cui

et al.

The Lancet Regional Health - Western Pacific, Journal Year: 2023, Volume and Issue: 37, P. 100849 - 100849

Published: July 25, 2023

Language: Английский

Citations

15
Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission DOI Creative Commons
Mehdi Benlarbi,

Shilei Ding,

Étienne Bélanger

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: July 2, 2024

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring its subvariants. Omicron subvariants are responsible for the vast majority SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% circulating strains as January 2024. To better understand parameters involved in viral transmission, we characterized functional properties Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, JN.1. We tested their capacity to evade plasma-mediated recognition neutralization, binding angiotensin-converting enzyme (ACE2), susceptibility cold inactivation, processing, well impact temperature on Spike-ACE2 interaction. found that compared early wild-type (D614G) strain, most subvariants' evolved escape neutralization by plasma individuals who received a fifth dose bivalent (BA.1 or BA.4/5) mRNA vaccine improve ACE2 binding, particularly at low temperatures. Moreover, had best affinity all temperatures tested. processing is associated inactivation. Intriguingly, was significantly growth rates humans. Overall, report Spikes newly emerged relatively stable resistant present improved which associated, temperatures, rates.IMPORTANCEThe gave rise wide range variants harboring new mutations glycoproteins. Several factors have been transmission fitness such plasma-neutralization whether additional could be importance variants' characterize several glycoprotein presents an further temperature. interaction strongly rate, such, represent another parameter affecting transmission.

Language: Английский

Citations

5
Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins DOI Creative Commons
Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(8), P. 887 - 887

Published: Aug. 5, 2024

Beginning in 2022, following widespread infection and vaccination among the global population, SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines past infections. This review covers convergent evolution of structural, nonstructural, accessory proteins SARS-CoV-2, with a specific look at common mutations found long-lasting infections that hint potentially reverting an enteric sarbecovirus type.

Language: Английский

Citations

5
Immune Evasion of SARS-CoV-2 Omicron Subvariants XBB.1.5, XBB.1.16 and EG.5.1 in a Cohort of Older Adults after ChAdOx1-S Vaccination and BA.4/5 Bivalent Booster DOI Creative Commons
Rafael Rahal Guaragna Machado, Erika Donizette Candido,

Andressa Simões Aguiar

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 144 - 144

Published: Jan. 30, 2024

The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report neutralizing activities 177 sera samples from 59 older adults, aged 62–97 years, 1 4 months after vaccination with a 4th dose ChAdOx1-S (Oxford/AstraZeneca) 3 5th Comirnaty Bivalent Original/Omicron BA.4/BA.5 (Pfizer-BioNTech). vaccination-induced antibodies neutralized efficiently ancestral D614G BA.4/5 variants, but to much lesser extent XBB.1.5, XBB.1.16, variants. results showed similar neutralization titers between were lower compared XBB.1.5. Sera same individuals boosted bivalent mRNA contained higher antibody titers, providing better cross-protection against Previous history infection during epidemiological waves BA.1/BA.2 BA.4/BA.5, poorly enhanced activity serum XBBs Our data highlight continued evasion recent subvariants support booster administration vaccine, as continuous strategy updating future doses match newly

Language: Английский

Citations

4
Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models DOI Open Access

Hong‐Yi Zheng,

Tian‐Zhang Song,

Yong‐Tang Zheng

et al.

动物学研究, Journal Year: 2024, Volume and Issue: 45(4), P. 747 - 766

Published: Jan. 1, 2024

The distribution of the immune system throughout body complicates

Language: Английский

Citations

4
Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants DOI Creative Commons

Hisano Yajima,

Tomo Nomai, Kaho Okumura

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(10)

Published: Sept. 16, 2024

ABSTRACT Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in human population, controlling COVID-19 pandemic has been challenging. Understanding how virus enhances its during a could offer valuable insights for more effective control viral epidemics. In this manuscript, we review evolution from early 2022 end 2023—from Omicron BA.2 XBB descendants. Focusing on period, provide concrete examples that increased by enhancing several functions spike (S) protein, including binding affinity ACE2 receptor and ability evade humoral immunity. Furthermore, explore specific mutations modify these S protein through structural alterations. This provides evolutionary, molecular, into repeatedly caused epidemic surges pandemic.

Language: Английский

Citations

4
Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1 DOI Creative Commons

Hisano Yajima,

Yuki Anraku,

Yu Kaku

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 7, 2024

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts up-conformation. However, whether also interacts with RBD down-conformation facilitate conformational shift RBD-up remains unclear. Herein, we present structures of BA.2.86 JN.1 proteins bound ACE2. Notably, successfully observed ACE2-bound down-RBD, indicating an intermediate structure before conformation. wider mobile angle RBDs up-state provides space interact facilitating transition state. K356T, but not N354-linked glycan, contributes both infectivity neutralizing-antibody evasion BA.2.86. These structural insights spike-protein dynamics would help understand mechanisms underlying infection neutralization.

Language: Английский

Citations

4
Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology DOI Creative Commons
Arthur Wickenhagen, Meaghan Flagg, Julia R. Port

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 11, 2025

Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion pre-existing immunity and decreased disease severity. Continuous evolution within raised concerns potential increased transmissibility and/or To address this, we evaluate fitness pathogenesis contemporary variants XBB.1.5, XBB.1.16, EG.5.1, JN.1 upper (URT) lower respiratory tract (LRT). We compare vivo infection Syrian hamsters primary human nasal lung epithelium cells assess differences transmissibility, antigenicity, innate immune activation. replicate efficiently URT but display limited pathology lungs compared to previous fail organoids. is attenuated both LRT other fails transmit male hamster model. Our data demonstrate that has favored URT.

Language: Английский

Citations

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