Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions.

ABSTRACT: A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the type I interferon (IFN-I) response and to downregulate major histocompatibility complex I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein, resulting in changes in virus pathogenesis.

SUBMITTER: Timilsina U

PROVIDER: S-EPMC10889720 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions.

Timilsina Uddhav U Ivey Emily B EB Duffy Sean S Plianchaisuk Arnon A The Genotype To Phenotype Japan G P-Japan Consortium Ito Jumpei J Sato Kei K Stavrou Spyridon S

International journal of molecular sciences 20240216 4

A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the type I interferon (IFN-I) resp ...[more]

PMID: 38397027

Similar Datasets

Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b.

Project description:SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is plausible to suggest that ORF7a or ORF7b could be used as biomarkers of progression in this pandemic.

| S-EPMC9597514 | biostudies-literature

Antibody evasion properties of SARS-CoV-2 Omicron sublineages.

Project description:The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 20211 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We2 and others3-6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2,3,5,6). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2-4,6). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).

| S-EPMC9021018 | biostudies-literature

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages.

Project description:SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

| S-EPMC9176643 | biostudies-literature

Zn-Induced Interactions Between SARS-CoV-2 orf7a and BST2/Tetherin.

Project description:We present in this work a first X-ray Absorption Spectroscopy study of the interactions of Zn with human BST2/tetherin and SARS-CoV-2 orf7a proteins as well as with some of their complexes. The analysis of the XANES region of the measured spectra shows that Zn binds to BST2, as well as to orf7a, thus resulting in the formation of BST2-orf7a complexes. This structural information confirms the the conjecture, recently put forward by some of the present Authors, according to which the accessory orf7a (and possibly also orf8) viral protein are capable of interfering with the BST2 antiviral activity. Our explanation for this behavior is that, when BST2 gets in contact with Zn bound to the orf7a Cys15 ligand, it has the ability of displacing the metal owing to the creation of a new disulfide bridge across the two proteins. The formation of this BST2-orf7a complex destabilizes BST2 dimerization, thus impairing the antiviral activity of the latter.

| S-EPMC8600262 | biostudies-literature

Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response.

Project description: Not available

| S-EPMC7815971 | biostudies-literature

Characterization of SARS-CoV-2 recombinants and emerging Omicron sublineages.

Project description:The SARS-CoV-2 Omicron is currently the predominant circulating variant in the COVID-19 pandemic. The dominating Omicron sublineages respond to host immune pressure and develop advantageous mutations or genetic recombination, which result in variants that are more contagious or better at escaping immune responses in response to previous infection or vaccination. Meanwhile, multiple genetic recombination events have been reported in coinfection cases, the majority of which have resulted from the recombination between co-circulating Omicron BA.1 (or BA.1.1) and Delta variant or BA.2. Here, we review the knowledge and characterization of recombination for SARS-CoV-2 at the population level, provide an update on the occurrence of newly circulating Omicron sublineages, and discuss the effectiveness of novel vaccines/therapeutic drugs against the Omicron variant.

| S-EPMC9812801 | biostudies-literature

Long COVID across SARS-CoV-2 variants, lineages, and sublineages.

Project description:This prospective study aimed to determine the prevalence of long COVID in patients hospitalized for SARS-CoV-2 infection from March 2020 to July 2022 and assess the impact of different viral lineages. A total of 2,524 patients were followed up for 12 months, with persistent symptoms reported in 35.2% at one month, decreasing thereafter. Omicron variant patients initially showed higher symptom intensity, but this trend diminished over time. Certain viral lineages, notably Delta lineages AY.126 and AY.43, and Omicron sublineages BA.1.17, BA.2.56, and BA.5.1, consistently correlated with more severe symptoms. Overall, long COVID prevalence and severity were similar across SARS-CoV-2 variants. Specific lineages may influence post-COVID sequelae persistence and severity.

| S-EPMC10995878 | biostudies-literature

SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns.

Project description:SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.

| S-EPMC9260412 | biostudies-literature

Ubiquitination of SARS-CoV-2 NSP6 and ORF7a Facilitates NF-κB Activation.

Project description:Patients with severe coronavirus disease 2019 tend to have high levels of proinflammatory cytokines, which eventually lead to cytokine storm and the development of acute respiratory distress syndrome. However, the detailed molecular mechanisms of proinflammatory cytokine production remain unknown. Here, we screened severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes and found that nonstructural protein 6 (NSP6) and open reading frame 7a (ORF7a) activated the NF-κB pathway. NSP6 and ORF7a interacted with transforming growth factor β-activated kinase 1 (TAK1), and knockout (KO) of TAK1 or NF-κB essential modulator (NEMO) abolished NF-κB activation by NSP6 and ORF7a. Interestingly, K61 of NSP6 was conjugated to K63-linked polyubiquitin chains by the E3 ubiquitin ligase tripartite motif-containing 13, and this polyubiquitination of NSP6 appeared crucial for recruitment of NEMO to the NSP6-TAK1 complex and NF-κB activation. On the other hand, ring finger protein 121 (RNF121) was required for the polyubiquitination of ORF7a. Knockdown of RNF121 significantly decreased ORF7a binding of TAK1 and NEMO, resulting in the suppression of NF-κB activation. Taken together, our results provide novel molecular insights into the pathogenesis of SARS-CoV-2 and the host immune response to SARS-CoV-2 infection. IMPORTANCE The detailed molecular basis of the induction of proinflammatory cytokines and chemokines by SARS-CoV-2 is unclear, although such induction is clearly related to the severity of COVID-19. Here, we show that SARS-CoV-2 NSP6 and ORF7a lead to NF-κB activation through associations with TAK1. K63-linked polyubiquitination of NSP6 and ORF7a by TRIM13 and RNF121, respectively, appears essential for NF-κB activation. These results suggest that inhibition of the NSP6 and ORF7a gene products may reduce the severity of COVID-19 symptoms by decreasing proinflammatory cytokine levels.

| S-EPMC9426613 | biostudies-literature

Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.

Project description:The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e. USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

| S-EPMC9848280 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data