Alphavirus

VIRION

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Enveloped, spherical, icosahedral, 65-70nm in diameter, capsid with a T=4 icosahedral symmetry made of 240 monomers. The envelope contains 80 spikes, each spike are trimer of E1/E2 proteins.
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GENOME

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Monopartite, linear, ssRNA(+) genome of 11-12 kb. The genome is capped and polyadenylated.

GENE EXPRESSION

The virion RNA is infectious and serves as both genome and viral messenger RNA. The whole genome is translated into a non-structural polyprotein which is processed by host and viral proteases. RdRp is expressed by suppression of termination at the end of 10% of nsP polyproteins. In late phase of infection, structural polyprotein is expressed through a subgenomic mRNA. The mRNA contains a Downstream Hairpin Loop (DLP)to avoid the translation shutoff induced by the host PKR in the late phase of infection. A truncated version of the structural polyprotein is produced by ribosomal frameshifting in the 6K region, the frameshift induces the translation of the TF protein .

REPLICATION

CYTOPLASMIC

  1. Attachement of the viral E glycoprotein to host receptors mediates clathrin-mediated endocytosis of virus into the host cell.
  2. Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.
  3. The positive-sense genomic ssRNA is translated into a polyprotein, which is cleaved into non-structural proteins necessary for RNA synthesis (replication and transcription).
  4. Replication takes place in cytoplasmic viral factories at the surface of endosomes. A dsRNA genome is synthesized from the genomic ssRNA(+).
  5. The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
  6. Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
  7. Capsid assembly occurs in cytoplasm.
  8. The capsid is envelopped by budding at the plasma membrane where the virion exits the cell .

Host-virus interaction

Chikungunya probably activates an autophagic process which promotes viral replication .

Host gene expression shutoff by virus

Togaviruses mediate host translation shutoff.
Alphaviruses induce strong PKR activation leading to leading to the almost complete phosphorylation of eIF2alpha and host translation arrest .

Alphaviruses perform host transcription shutoff by inhibiting host RNA polymerase II. Host RNA-pol II catalytic subunit is targeted for degradation as early as 4-6h p.i. .