ArticleJournal of virology2007
The 29-nucleotide deletion present in human but not in animal severe acute respiratory syndrome coronaviruses disrupts the functional expression of open reading frame 8.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 115 citations in OpenAlex.
- The disappearance of ORF8 in human-adapted coronaviruses: the Cheshire cat paradigm.Virus genes · 2026Article
- Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.Molecular biology research communications · 2025Article
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- Glycosylated, Lipid-Binding, CDR-Like Domains of SARS-CoV-2 ORF8 Indicate Unique Sites of Immune Regulation.Microbiology spectrum · 2023Article
- The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection.BMC genomics · 2023Article
- The relevant information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the five-question approach (when, where, what, why, and how) and its impact on the environment.Environmental science and pollution research international · 2023Review
- Review
- Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes.Microorganisms · 2023Article
- Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.Frontiers in cellular and infection microbiology · 2023Review
- Attenuated Viral Replication of AvianMicrobiology spectrum · 2022Article
- Article
- Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2.The international journal of biochemistry & cell biology · 2022Review
- SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer.The Journal of biological chemistry · 2022Article
- Structural, genomic information and computational analysis of emerging coronavirus (SARS-CoV-2).Bulletin of the National Research Centre · 2022Review
- Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins-A Possible Signature of Adaptive Selection.Frontiers in genetics · 2022Article
- RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers inRNA biology · 2022Article
- Comparative highlights on MERS-CoV, SARS-CoV-1, SARS-CoV-2, and NEO-CoV.EXCLI journal · 2022Review
- Inflammasome activation at the crux of severe COVID-19.Nature reviews. Immunology · 2021Review
- Immunoinformatic analysis of structural and epitope variations in the spike and Orf8 proteins of SARS-CoV-2/B.1.1.7.Journal of medical virology · 2021Article
- Mutational analysis of SARS-CoV-2Gene reports · 2021Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most striking and dramatic genomic changes observed in the severe acute respiratory syndrome coronavirus (SARS-CoV) isolated from humans soon after its zoonotic transmission from palm civets was the acquisition of a characteristic 29-nucleotide deletion. This occurred in open reading frame 8 (ORF8), one of the accessory genes unique to the SARS-CoV. The function of ORF8 and the significance of the deletion are unknown. The intact ORF8 present in animal and some early human isolates encodes a 122-amino-acid polypeptide (8ab(+)), which we expressed in cells using the vaccinia virus T7 expression system. It was found to contain a cleavable signal sequence, which directs the precursor to the endoplasmic reticulum (ER) and mediates its translocation into the lumen. The cleaved protein became N-glycosylated, assembled into disulfide-linked homomultimeric complexes, and remained stably in the ER. The 29-nucleotide deletion splits ORF8 into two ORFs, 8a and 8b, encoding 39- and 84-residue polypeptides. The 8a polypeptide is likely to remain in the cytoplasm, as it is too small for its signal sequence to function and will therefore be directly released from the ribosome. However, we could not confirm this experimentally due to the lack of proper antibodies. ORF8b appeared not to be expressed in SARS-CoV-infected cells or when expressed from mRNA's mimicking mRNA8. This was due to the context of the internal AUG initiation codon, as we demonstrated after placing the ORF8b immediately behind the T7 promoter. A soluble, unmodified and monomeric 8b protein was now expressed in the cytoplasm, which was highly unstable and rapidly degraded. Clearly, the 29-nucleotide deletion disrupts the proper expression of the SARS-CoV ORF8, the implications of which are discussed.
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