Betaarterivirus (taxid:2499674)

VIRION

Enveloped, spherical, about 45-60 nm in diameter. The virion is comprised of an isometric core of 20-30 nm surrounded by a lipid-containing envelope. The RNA genome associates with the N protein to form the nucleocapsid.

GENOME

Monopartite, linear, ssRNA(+) genome of 14-16kb in size, 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.

Enzymes: EndoU ribonuclease

GENE EXPRESSION

The virion RNA is infectious and serves as both genome and viral messenger RNA. ORF1b is translated by a ribosomal frameshifting. Polyproteins 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. The mRNA2 is bicistronic. PRRSV also expresses a truncated polyprotein 1aTF due to a ribosomal frameshifting in the nsp2 gene.
Protein GP2 and 5a are produced by leaky scanning from the E and gp5 subgenomic mRNA respectively.

ENZYMES

• RNA-directed RNA polymerase [Q04561]
• Nido-type capping (GDP polyribonucleotidyltransferase, N7methyltransferase, 2'O methylase) [Q04561]
• EndoU ribonuclease [Q04561]
• Polyprotein major protease (Peptidase S32) [Q04561]
• Proteases (Peptidase C31, Peptidase C32, Peptidase C33) [Q04561]
• Helicase [Q04561]

REPLICATION

CYTOPLASMIC

1. Attachement to host receptors mediates clathrin-mediated endocytosis of the virus into the host cell.
2. Fusion of virus membrane with the endosomal membrane. ssRNA(+) genome is released into the cytoplasm.
3. Synthesis and proteolysis of replicase polyproteins.
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 ESCRT-independent budding at the membranes of endoplasmic reticulum (ER), intermediate compartments, and/or Golgi complex.
8. Release of new virions by exocytosis.

Host-virus interaction

Apoptosis modulation

PRRSV induces apoptosis via host caspases activation (caspase-8 and mitochondria-dependent caspase-9)

Autophagy modulation

PRRSV induces autophagy to promote virus replication .

Innate immune response inhibition

PRRSV clearly inhibits the type-I IFN response and down-regulates TLR3, TLR7, and TLR8 expression.
At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) play roles in the IFN suppression and NF-κB pathways :

Nsp1α subunit inhibits the IκB phosphorylation in the cytoplasm and therefore the activation of NF-κB.

Nsp1β inhibits phosphorylation of STAT1 and nuclear translocation of ISGF3 complex (composed of STAT1, STAT2 and IRF9). Nsp1β prevents IRF3 activation, thereby interfering with the RIG-I signaling pathway .

Nsp2 inhibits IFN production by blocking the ubiquitinylation of phosphorylated IκB and phosphorylation of IRF3 through the OTU domain. Nsp2 has the potential to deconjugate ISGylation.

Nsp11 suppresses IFN-β production through degradation of IPS-1 mRNA. For the second wave of IFN signaling, PRRSV Nsp1β blocks the phosphorylation of STATs and inhibits the nuclear translocation of ISGF3 complex (composed of STAT1, STAT2 and IRF9).