Mastadenovirus (taxid:10509)

VIRION

Non-enveloped capsid with a pseudo T=25 icosahedral symmetry . The capsid diameter is about 90 nm. The capsid shell consists of 720 hexon subunits arranged as 240 trimers and 12 vertex penton capsomers each with a fiber protruding from the surface.

• Double jelly roll-fold major capsid protein [Hexon]
• Single jelly roll-fold penton capsid protein [Penton]

GENOME

Monopartite, linear double-stranded DNA of 35-36kb encoding about 40 proteins. The genome has terminally redundant sequences which have inverted terminal repetitions (ITR). The terminal protein (TP) is covalently attached to each end of the genome.

GENE EXPRESSION

Transcription is nuclear, in three phases; early, intermediate (replication), and late (virion assembly). All genes are transcribed by host RNA pol II except virus-associated (VA) gene(s) of some primate adenoviruses transcribed by RNA pol III. Genes transcribed by RNA pol II give rise to multiple mRNA that are produced by alternative splicing and use of different poly(A) sites.

ENZYMES

• DNA-directed DNA polymerase B [POL]
• Protein-primed terminal transferase [POL on TP]
• Adenain (Peptidase C5) [Protease]

REPLICATION

NUCLEUS

1. Attachment of the viral fibers to the host CAR adhesion receptor. Subsequent binding of the penton protein to host integrin entry receptors mediates internalization into the host cell by clathrin-mediated endocytosis of the virus and fiber shedding. Some serotypes also seem to use macropinocytosis.
2. Disruption of host endosomal membrane by lytic protein VI releases the viral capsid in the cytosol.
3. Microtubular transport toward nucleus of the viral genome still protected by the core protein VII and a partial capsid mainly composed of hexons and protein IX.
4. Docking at the NPC and capsid disruption.
5. Import of the viral genome into host nucleus mediated by core protein VII.
6. Transcription of early genes (E genes) by host RNA pol II: these proteins optimize the cellular milieu for viral replication, and counteract a variety of antiviral defenses.
7. Intermediate genes activate replication of the DNA genome by DNA strand displacement in the nucleus.
8. Expression of L4-22K and L4-33K causes early to late switch. Transcription of late genes (L genes) by host RNA pol II, mostly encoding structural proteins.
9. Host translation shutoff performed by the viral 100K protein.
10. Assembly of new virions in the nucleus.
11. Virions are released by lysis of the cell.
12. Virion maturation by the viral protease.