دورية أكاديمية
أعرض في EDS

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion.

التفاصيل البيبلوغرافية
العنوان: Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion.
المؤلفون: Neches RY; DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley California, USA., Kyrpides NC; DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley California, USA., Ouzounis CA; Biological Computation and Process Laboratory, Chemical Process and Energy Resources Institute, Centre for Research and Technology Hellas, Thessalonica, Greece ouzounis@certh.gr.
المصدر: MBio [mBio] 2021 Jan 19; Vol. 12 (1). Date of Electronic Publication: 2021 Jan 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Immune Evasion*, COVID-19/*immunology , SARS-CoV-2/*genetics , SARS-CoV-2/*immunology , Viral Proteins/*immunology, Animals ; COVID-19/virology ; Databases, Genetic ; Evolution, Molecular ; Genome, Viral ; Humans ; Phylogeny ; Sequence Alignment ; Viral Proteins/genetics
مستخلص: Orf8, one of the most puzzling genes in the SARS lineage of coronaviruses, marks a unique and striking difference in genome organization between SARS-CoV-2 and SARS-CoV-1. Here, using sequence comparisons, we unequivocally reveal the distant sequence similarities between SARS-CoV-2 Orf8 with its SARS-CoV-1 counterparts and the X4-like genes of coronaviruses, including its highly divergent "paralog" gene Orf7a, whose product is a potential immune antagonist of known structure. Supervised sequence space walks unravel identity levels that drop below 10% and yet exhibit subtle conservation patterns in this novel superfamily, characterized by an immunoglobulin-like beta sandwich topology. We document the high accuracy of the sequence space walk process in detail and characterize the subgroups of the superfamily in sequence space by systematic annotation of gene and taxon groups. While SARS-CoV-1 Orf7a and Orf8 genes are most similar to bat virus sequences, their SARS-CoV-2 counterparts are closer to pangolin virus homologs, reflecting the fine structure of conservation patterns within the SARS-CoV-2 genomes. The divergence between Orf7a and Orf8 is exceptionally idiosyncratic, since Orf7a is more constrained, whereas Orf8 is subject to rampant change, a peculiar feature that may be related to hitherto-unknown viral infection strategies. Despite their common origin, the Orf7a and Orf8 protein families exhibit different modes of evolutionary trajectories within the coronavirus lineage, which might be partly attributable to their complex interactions with the mammalian host cell, reflected by a multitude of functional associations of Orf8 in SARS-CoV-2 compared to a very small number of interactions discovered for Orf7a. IMPORTANCE Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8. Orf7a is a potential immune antagonist of known structure, while a deletion of Orf8 was shown to decrease the severity of the infection in a cohort study. The subtle sequence similarities imply that Orf8 has the same immunoglobulin-like fold as Orf7a, confirmed by structure determination. We characterize the subgroups of this superfamily and demonstrate the highly idiosyncratic divergence patterns during the evolution of the virus.
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فهرسة مساهمة: Keywords: Orf7a; Orf8; SARS-CoV-2; X4-like; coronavirus; protein superfamily; structure prediction; virus evolution
المشرفين على المادة: 0 (ORF7a protein, SARS-CoV-2)
0 (ORF8 protein, SARS-CoV-2)
0 (Viral Proteins)
تواريخ الأحداث: Date Created: 20210120 Date Completed: 20210303 Latest Revision: 20240806
رمز التحديث: 20240806
مُعرف محوري في PubMed: PMC7845636
DOI: 10.1128/mBio.03014-20
PMID: 33468697
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mBio.03014-20