ArticleThe Journal of biological chemistry2022
SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells.Science advances · 2026Article
- Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 ORF8: an accessory protein at the interface of immune evasion and inflammation.Frontiers in immunology · 2026Review
- HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation.Nature communications · 2025Article
- The Recurring Loss of ORF8 Secretion in Dominant SARS-CoV-2 Variants.International journal of molecular sciences · 2025Article
- Yip1 interacting factor homolog B mediates the unconventional secretion of ORF8 during SARS-CoV-2 infection.iScience · 2025Article
- Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.Molecular biology research communications · 2025Article
- Vitamin D-inducible antimicrobial peptide LL-37 binds SARS-CoV-2 Spike and accessory proteins ORF7a and ORF8.Frontiers in cellular and infection microbiology · 2025Article
- Article
- Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model.Virologica Sinica · 2024Article
- Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses.Journal of nanobiotechnology · 2024Review
- Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.Nature communications · 2024Article
- The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm.Journal of molecular cell biology · 2024Article
- SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms.Viruses · 2024Review
- Characterization of antibody response to SARS-CoV-2 Orf8 from three waves of COVID-19 outbreak in Thailand.PloS one · 2024Article
- One for all-human kidney Caki-1 cells are highly susceptible to infection with corona- and other respiratory viruses.Journal of virology · 2023Article
- A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.Nature communications · 2023Article
- Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis.iScience · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ORF8 is an accessory protein encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consensus regarding the biological functions of ORF8 is lacking, largely because the fundamental characteristics of this protein in cells have not been determined. To clarify these features, we herein established an ORF8 expression system in 293T cells. Using this system, approximately 41% of the ORF8 expressed in 293T cells were secreted extracellularly as a glycoprotein homodimer with inter/intramolecular disulfide bonds. Intracellular ORF8 was sensitive to the glycosidase Endo H, whereas the secreted portion was Endo-H-resistant, suggesting that secretion occurs via a conventional pathway. Additionally, immunoblotting analysis showed that the total amounts of the major histocompatibility complex class Ι (MHC-I), angiotensin-converting enzyme 2 (ACE2), and SARS-CoV-2 spike (CoV-2 S) proteins coexpressed in cells were not changed by the increased ORF8 expression, although FACS analysis revealed that the expression of the cell surface MHC-I protein, but not that of ACE2 and CoV-2 S proteins, was reduced by ORF8 expression. Finally, we demonstrate by RNA-seq analysis that ORF8 had no significant stimulatory effects in human primary monocyte-derived macrophages (MDMs). Taken together, our results provide fundamental evidence that the ORF8 glycoprotein acts as a secreted homodimer, and its functions are likely associated with the intracellular transport and/or extracellular signaling in SARS-CoV-2 infection.
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