Reduced CpG |
|
|
Decreased activity of ZAP and APOBEC3G |
ZAP expressed
in immune cells |
(25) |
ORF1a |
nsp1 |
Mediates RNA replication and processing. Involved in RNA
degradation. |
Modulates calcineurin/ NFAT pathway. Cleaves host RNA.
Inhibits cyclophilins and immunophilins. Blocks ATF2/c-Jun, IRF3 and
IRF7, NFκB, decreases STAT1 phosphorylation. Interferes with RIG-1
pathway. |
Associated with immune pathogenicity and long-term cytokine
dysregulation. Promotes host RNA degradation. |
(34–36) |
|
nsp2 |
Replicase essential for proofreading replication. |
May bind to
prohibitin 1 and 2, involved in apoptosis, mitochondrial biogenesis and
intracellular signalling. Modulates host survival signalling. |
Associated with pathogenicity. Deletion attenuates viral growth and RNA
synthesis. |
(37,38) |
|
nsp3
|
Papain like protease (PLpro). Processes pp1a and pp1ab.
Complexes with nsp4 and nsp6.
|
Deubiquitinates and deISGylates host proteins Blocks IFNa, IFNβ, CXCL10
and CCL5. Inhibits TLR7 signalling by removing Lys63-linked
polyubiquitination of TRAF3 and 6.
Antagonizes IRF3, stabilizes IκBα thereby blocking NFκB signalling.
Interacts with STING-TRAF-TBK1 complex.
|
Forms DMV and replication process evade innate immune recognition.
|
(33,39,40)
|
|
nsp4 |
Complexes with nsp3 and nsp6 to form the DMV. May anchor RTC to
ER. |
Helps replication process evade innate immune recognition. |
|
(39) |
|
nsp5
|
Chymotrypsin
-like protease (3CLpro)
|
Induces apoptosis and growth arrest via caspase-3 and caspase-9.
|
|
(41)
|
|
nsp6 |
Complexes with nsp3 and nsp4 to form DMV. |
Helps replication
process evade innate immune recognition. Activates autophagosome. |
|
(39) |
|
nsp7 |
Complexes with nsp8 and nsp12 for viral replication |
|
Nsp7-nsp8 form the primase complex. |
(42) |
|
nsp8 |
Complexes with nsp7 and nsp 12 for viral replication |
|
Nsp7-nsp8 form the primase complex. |
(42) |
|
nsp9 |
Involved in viral genomic RNA reproduction but exact role
unclear |
|
Interacts with nsp8 |
(43,44) |
|
nsp10
|
Complexes with nsp 1,7 and 14. Multifunctional cofactor in
replication.
|
Interacts with the oxido-reductase system causing cytopathic effect.
Aids RNA capping thus evades RIG-1 and MDA5 recognition.
|
Activator of nsp14 function.
Forms a complex with nsp16.
|
(26,45,
46)
|
|
nsp11 |
Peptide resulting from cleavage of pp1a at nsp10/11 junction |
Not known |
|
|
ORF1b
(nsps in addition to 1-11)
|
nsp12
|
RNA dependent
RNA polymerase (RdRp)
|
Targeting mitochondria limits host cellular responses
|
|
(42)
|
|
nsp13 |
helicase key for efficient replication of viral genome |
Caps
RNA thus evades RIG-I and MDA-5 signalling |
Failure to trigger IFIT1. |
(47) |
|
nsp14
|
exon 3′–5′ exonuclease plays crucial role in viral RNA synthesis and
capping. Complexes with nsp10.
|
Involved in the capping through its function as a guanine-N7
methyltransferase helping nsp16 evade RIG-1 and MDA5 recognition.
|
|
(48)
|
|
nsp15
|
uridylate -specific endoribonuclease
(EndU)
|
Limits exposure of viral dsRNA to the sensors MDA5, PKR, and OAS/RNaseL.
Inhibits poly U thereby evading MDA5 thus antagonizing IFN-a/β
production.
|
|
(28)
|
|
nsp16 |
2’-O-ribose methyl transferase involved in RNA capping.
Complexes with nsp10. |
Caps RNA thus evades RIG-I and MDA-5 signalling |
Failure to trigger IFIT1 |
(26,49) |
ORF2
|
spike
|
Heavily glycosylated with 22 glycans.
ACE/ACE-2 interaction.
Requires priming to expose membrane fusion
|
Masks immunogenic protein epitopes.
Induced misbalanced in RAS that triggers inflammation.
Masks immunogenic protein epitopes.
|
|
(22,23,
50, 51)
|
ORF3a
|
ORF3a
|
Interact with SARS-CoV M, S, E, and 7a proteins
Forms viroporins
|
Activates PERK pathway, triggers apoptosis through expression of ATF4
and CHOP. Downregulates and degrades Type 1 IFNR.
|
Expressed on cell surface. Induces fibrinogen, stress pathways, necrotic
cell death, activates inflammasome.
|
(24,52–54)
|
ORF4 |
Envelope |
Essential for viral assembly and budding. Forms
viroporins. |
Induces ROS and activates inflammasome |
|
(55,56) |
ORF5 |
Membrane |
Important for viral assembly |
Inhibits type I
interferon production by impeding the formation of TRAF3. TANK.
TBK1/IKKepsilon complex |
Induces apoptosis. |
(57–59) |
ORF6
|
ORF6
|
Plays a role in viral pathogenesis, interacts with ORF8. May aid viral
virulence.
|
Inhibits STAT1
nuclear import
|
Promotes RNA polymerase activity
|
(53)
|
ORF7a
|
ORF7a
|
Interacts with S protein and p3a.
Not essential for replication
|
Inhibits BST-2 glycosylation, leading to a loss of BST-2’s function.
SARS-CoV ORF7a induces caspase-dependent apoptosis.
|
BST -2 restricts virion egress by tethering virions to plasma membrane.
Interacts with LFA.
|
(60,61)
|
ORF7b |
ORF7b |
Not essential for viral replication but structural
component of the virion. |
|
It is an integral membrane protein located
in the Golgi compartment. |
(62) |
ORF8 |
ORF8 |
Differs form other HCoVs |
Interact and downregulates
MHC-I |
SARS-CoV encodes p8a and p8b that induce caspase-dependent
apoptosis and activates UPR. |
(63) |
ORF9
|
Nucleo-capsid
|
Stabilises viral RNA.
Interacts with stress granules G3BP1.
|
Targets MAVS -TRAF3-TRAF6 and antagonizes IFN-β
|
|
(53,64,
65)
|
ORF10 |
ORF10 |
Ubiquitin ligase |
unknown |
|
|