Table 14.19 Functions and properties of coronavirus proteins
From: Viruses with Single-Stranded, Positive-Sense RNA Genomes
Reading frame | Protein | Size | Properties | Function |
|---|---|---|---|---|
ORF1a | NSP1 | 180 aa | Virulence factor; activity described only in SARS-CoV, causes degradation of cellular RNA and allows the virus to replicate unimpaired, blocks the synthesis of IFN-α and IFN-β | |
NSP2 | 638 aa | ? | Function unclear; interaction with the cellular proteins prohibitin 1 and prohibitin 2; deletion has no effect on replication | |
PL1pro | ? | Papain-like cysteine protease; autocatalytic cleavage of the N-terminal domain from pp1a and pp1ab (not in SARS-CoV) | ||
NSP3/PL2pro | 1,922 aa | Zinc finger motif, 180–200 kDa | Papain-like cysteine protease; cleaves pp1a and pp1ab between NSP2 and NSP3; causes protein deubiquitylation; ADP phosphatase activity | |
NSP4 | 500 aa | Membrane-associated | Influences formation of intracellular membrane vesicles, active in virus morphogenesis? | |
NSP5/3CLpro | 306 aa | 30 kDa, dimer | Serine protease with homology to 3C protease of picornaviruses; principal protease | |
NSP6 | 290 aa | Hydrophobic, transmembrane domain | ? | |
NSP7 | 83 aa | Forms supercomplexes with NSP8 | ? | |
NSP8 | 198 aa | Forms supercomplexes with NSP7, nucleic acid binding properties | Alternative RNA-dependent RNA polymerase to NSP12; primase activity for primer synthesis in genome replication and translation? | |
NSP9 | 113 aa | Forms homodimers, interaction with NSP8 | ? | |
NSP10 | 139 aa | Zinc finger motif, nucleic acid binding properties | ? | |
NSP11 | 13 aa | ? | ? | |
ORF1b | NSP12/RNA-dependent RNA polymerase | 932 aa | 106 kDa | Synthesis of genomic and subgenomic RNA species |
NSP13/RNA helicase | 601 aa | Zn2+ ion-binding, 67 kDa | ssRNA/dsRNA helicase; NTPase, dNTPase; necessary for genome replication | |
NSP14/3–5′ exoribonuclease (ExoN) | 527 aa | Exoribonuclease, active during RNA synthesis, possibly involved in recombination and repair processes | ||
NSP15/endo-ribonuclease (NendoU) | 346 aa | Uridylate-specific endoribonuclease; active during RNA synthesis | ||
NSP16 | 298 aa | Active during 5′ capping of mRNAs and viral genomes | ||
ORF2a | 2a (mouse hepatitis virus) | 30 kDa | Non-structural protein | Cyclic phosphodiesterase, RNA processing |
ORF2 | S | 180–200 kDa | Glycosylated membrane protein; trimer; located in virus and plasma membrane of infected cells | Viral attachment/receptor binding Induces membrane fusion Induces production of neutralizing antibodies ADCC response |
ORF2.1 | HE | 65–70 kDa | Glycosylated membrane protein, present in most betacoronaviruses (not in SARS-CoV) | Haemagglutinin and esterase responsible for secondary adherence to acetylated neuramic acid residues |
ORF3 | 3a | 274 aa | Membrane protein, O-glycosylated; tetramer; component of virus particles | Ion channel protein; induces production of proinflammatory cytokines in SARS-CoV |
3b | 154 aa | Transport into nucleus | Function unclear; inhibits production of IFN-α and IFN-β? | |
ORF4 | E | 9–12 kDa | Membrane protein | Necessary for particle assembling, ion channel protein (viroporin), in some coronaviruses proapoptotic |
ORF5 | M | 20–30 kDa | Glycosylated membrane protein; localized in ER and viral membranes of infected cells | Interaction with N protein Initiates viral morphogenesis by budding within the ER lumen |
ORF6 | ORF6 | 63 aa | Betacoronaviruses (SARS-CoV): associated with ER membrane and Golgi vesicles, component of the virus particle Alphacoronaviruses and gammacoronaviruses: non-structural protein, function unclear | Function unclear; interaction with karyopherin-α2, whereby there is inhibition of nuclear transport of Stat1? |
ORF7 | 7a | 122 aa | Localized in ER/ERGIC/Golgi, also component of the virus particle, interaction with M/E proteins, and with other ancillary or cellular proteins | Apoptosis induction, activation of cellular kinases, interaction with BiP and proteasome |
7b | 44 aa | Membrane protein (SARS-CoV), detectable in virus particles, in infected cells in Golgi vesicles | Function unclear | |
ORF8 | 8ab 8a 8b | SARS-CoV isolated from animals (civet cats, bats) contain a continuous ORF8 producing a single 8ab protein; in human isolates ORF8 contains a deletion of 29 nucleotides, thus generating ORFa and ORFb | Function unknown | |
ORF9 | N | 60–70 kDa | Phosphorylated, dimeric, strongly basic, localization cell type-specific, also in the nucleus | Binding to the RNA genome forming helical nucleocapsids Interaction with the cytoplasmic domain of M protein Interaction with smad3, interferes with cellular transcription and cell cycle regulation |
9b | Function unclear; morphogenesis? |