Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect
many species, including humans, other mammals, and birds. After infection, the
host may develop respiratory, bowel, liver, and neurological diseases.
Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus,
γcoronavirus, and Deltacoronavirus. The ideal hosts of αCoV and
βCoV are mammals, and γCoV primarily infects birds, while DeltaCoV has
been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and
Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the
Sarbecovirus subgenus of βCoV [E1].
All coronaviruses have a similar genomic structure. At the 5' end, two-thirds
of the genome comprises two large open reading frames (ORFs) (ORF1a and ORF1b)
encoding the coronavirus replicase, which is highly conserved among genera. At
the 3' end, the genome encodes four structural proteins (S, E, M and N) and a
variable number of accessory proteins. Accessory proteins play an important
role in virus–host interactions, especially in antagonizing or regulating host
immunity and virus adaptation to the host. There are large variations in the
number of accessory proteins (1–10) among coronaviruses. The number of
accessory proteins of the αCoVs is relatively lower, between 1 and 5,
while βCoVs have 3–5 accessory proteins, except for SARS-CoV and
SARS-CoV-2, which possess the largest number of accessory proteins among all
coronaviruses (10 and 9, respectively). ORF8 is the most variable accessory
protein among those encoded by SARS related coronaviruses (SARSr-CoVs) and is
not shared by all members of subgenus Sarbecovirus. SARSr ORF8 accessory
proteins are characterized by the presence of an N-terminal hydrophobic signal
peptide, a conserved N-glycosylation site, and enough cysteine residues with
the potential to form disulfide bonds, drawing their picture as structurally
stable potential ER-resident proteins. There is functional overlap between
these proteins with involvement in immune modulation, which is probably
accomplished through involvement in protein quality control. When ORF8 is
exogenously overexpressed in cells, it disrupts IFN-I signaling. Unlike
ORF8a/b of SARS-CoV, the SARS-CoV-2 ORF8 downregulates MHC-I in cells. The
SARSr ORF8 contains an immunoglobulin (Ig)-like domain (see <PDB:7JTL>)
[1,2,3,4,5].
The profile we developed covers the entire SARS ORF8 accessory protein Ig-like
domain.
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