Orthopoxvirus (taxid:10242)

VIRION

Enveloped, brick-shaped virion, 250nm long and 200nm wide. The surface membrane displays surface tubules or surface filaments. Two distinct infectious virus particles exists: the intracellular mature virus (IMV) and the extracellular enveloped virus (EEV).

GENOME

Linear, dsDNA genome of 170-250kb. The linear genome is flanked by inverted terminal repeat (ITR) sequences which form covalently closed hairpin termini at each extremity.

GENE EXPRESSION

ENZYMES

• DNA-directed DNA polymerase [E9L (OPG071)]
• DNA-directed RNA polymerase [E4L (OPG066)]
• Cell-type capping
  • RNA TPase [D1R (OPG113)]
  • GTase [D1R (OPG113)]
  • N7MTase [D1R (OPG113) + D12L (OPG124)]
  • 2'O methylase [J3R (OPG102)]
• Core protease (Peptidase C57) [I7 (OPG083)]
• Metalloprotease (Peptidase M44) [G1L (OPG085)]
• Phospholipase [F13 (OPG057)]

REPLICATION

CYTOPLASMIC

1. Attachement of the viral proteins to host glycosaminoglycans (GAGs) mediates endocytosis of the virus into the host cell. The virus can be uptaked also by apoptotic mimicry
2. Fusion with the plasma membrane to release the core into the host cytoplasm.
3. Early phase: early genes are transcribed in the cytoplasm by viral RNA polymerase. Early expression begins at 30 minutes post-infection.
4. Core is completely uncoated as early expression ends, viral genome is now free in the cytoplasm.
5. Intermediate phase: Intermediate genes are expressed, triggering genomic DNA replication at approximately 100 minutes post-infection.
6. Late phase: Late genes are expressed from 140 min to 48 hours post-infection, producing all structural proteins.
7. Assembly of progeny virions starts in cytoplasmic viral factories, producing an spherical immature particle. This virus particle matures into brick-shaped intracellular mature virion (IMV).
8. IMV virion can be released upon cell lysis, or can acquire a second double membrane from trans-Golgi and bud as external enveloped virion (EEV).

Host-virus interaction

Adaptive immune response inhibition

The vaccinia virus A35R localizes to host endosomes and inhibits MHC class II antigen presentation .

Apoptosis modulation

Several poxviral proteins are dedicated to the inhibition of host apoptosis. Vaccinia F1L functions both as a suppressor of proapoptotic Bcl-2 family proteins and as an inhibitor of caspase-9 .

Autophagy modulation

Vaccinia virus actively disrupts the cellular autophagy through a mechanism that involves aberrant LC3 lipidation and a direct conjugation between ATG12 and ATG3 .

NF-kappa-B modulation

The B14 protein from vaccinia virus functions by binding to the IKK complex via an interaction with IKK-beta and preventing the phosphorylation of IKK-beta on its activation loop. In turn, IKK-beta is not activated and fails to phosphorylate IkB-beta, leaving IkB-beta able to retain NF-kappa-B in the cytoplasm .

Innate immune response inhibition

Poxviruses inhibit the cascade leading to production of interferon-beta by mainly targeting the host IRF3 protein. For instance, vaccinia virus protein C6 inhibits IRF3 activation downstream of TBK1 .