Coronaviridae (taxid:11118)

VIRION

Enveloped, spherical, about 120 nm in diameter. The RNA genome is associated with the N protein to form the nucleocapsid (helical for the genus coronavirus, and tubular for the genus torovirus) see Neuman BW et al. for virion cryo-electron microscopy analysis.

GENOME

Monopartite, linear ssRNA(+) genome of 27-32kb in size (the largest of all RNA virus genomes). Capped, and polyadenylated. The leader RNA (65-89 bp) at the 5' end of the genome is also present at the end of each subgenomic RNAs.

GENE EXPRESSION

The virion RNA is infectious and serves as both the genome and viral messenger RNA.

Genomic RNA encodes for ORF1a, as for ORF1b, it is translated by ribosomal frameshifting. Resulting proteins pp1a and pp1ab are processed into the viral polymerase (RdRp) and other non-structural proteins involved in RNA synthesis. Structural proteins are expressed as subgenomic RNAs. Each RNA (genomic and subgenomic) is translated to yield only the protein encoded by the 5'-most ORF.

ENZYMES

• RNA-dependent RNA polymerase [P0DTD1]
• Proofreading exoribonuclease (ExoN) [P0DTD1]
• Nido-type capping (GDP polyribonucleotidyltransferase, N7methyltransferase, 2'O methylase) [P0DTD1]
• Protein-primed initiation of RNA synthesis [on nsp9 by nsp12]
• EndoU ribonuclease [P0DTD1]
• Papain-like protease (Peptidase C16) [P0DTD1]
• 3C-like proteinase (Peptidase C30) [P0DTD1]
• Helicase [P0DTD1]
• ADP-Ribosylhydrolase [P0DTD1]

REPLICATION

CYTOPLASMIC

1. Attachment of the viral S protein (maybe also HE if present) to host receptors mediates endocytosis of the virus into the host cell.
2. Fusion of virus membrane with the endosomal membrane (probably mediated by S2), ssRNA(+) genome is released into the cytoplasm.
3. Synthesis and proteolytic cleavage of the replicase polyprotein.
4. Replication occurs in viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+).
5. The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
6. Synthesis of structural proteins encoded by subgenomic mRNAs.
7. Assembly and budding at membranes of the endoplasmic reticulum (ER), the intermediate compartments, and/or the Golgi complex.
8. Release of new virions by exocytosis.

Host-virus interaction

Host gene expression shutoff

SARS-CoV nsp1 protein mediates host mRNA decay .

Apoptosis modulation

Human coronavirus induces neuronal apoptosis via mitochondrial apoptosis-inducing factor and cyclophilin D .

IBV also seems to induce apoptosis at late stages of the infection cycle .

Autophagy modulation

Infectious bronchitis virus (IBV), SARS-CoV and MHV nsp6 proteins induce autophagy to promote virus replication .

Cell-cycle modulation

SARS-CoV Nsp15 has a retinoblastoma protein-binding motif (LXCXE/D) and seems to interact with host retinoblastoma protein resulting in an increased proportion of cells in the S phase of the cell cycle. This probably involves G1/S host cell cycle checkpoint dysregulation by the virus .

IBV induces a both S-phase and G(2)/M-phase arrest in infected cells to promote favorable conditions for viral replication .

Murine coronavirus and SARS-CoV may also induce G0/G1 checkpoint dysregulation .

Innate immune response inhibition

SARS-CoV Protein 3a, which has a viral channel activity, may cause endoplasmic reticulum stress and inhibition of the type 1 interferon receptor .

SARS-CoV PL-Pro mediates ISG15 inhibition and inhibition of host IRF3 .

SARS-CoV M protein mediates the inhibition of host TRAF3 .

TGEV protein 7 may counteract host antiviral response .