1. Adenoviruses
Chapter 32

2. Properties of Adenoviruses
Structure
Icosahedral
70-90 nm diameter
Double-stranded DNA, kb
More than 20 proteins
Nonenveloped
Classification
Aviadenovirus (Birds)
Mastadenovirus (mammals)
49 serotypes isolated from humans
Hemagglutination (HA) and inhibition (HI) tests
Six groups (A-F) (Table 32-2)

3. Adenovirus Replication
Attachment and entry
Spike protein fibers mediate cell attachment
Fibers induce toxin-like effects in vitro (cell detachment)
The fibers are responsible for HA activity
Taken into the cell by receptor-mediated endocytosis (endosomes)
Virus escapes the endosome to gain access to the cytoplasm
The acidic pH of the endosome triggers escape, probably by modulating the activity of viral enzyme (endoprotease) that disrupts the endosome membrane
The viral hexon protein delivers the viral DNA to the cell’s nucleus

4. Adenovirus Replication

5. Adenovirus Replication
Replication (cont.)
Early events
Cell is stimulated into S phase
Genes are encoded on both strands of the viral genome
The E genes (“early”) are responsible for seizing control of the cell
The E1A and E1B regions encode several proteins that disable cellular tumor suppressor genes in the cell
By disabling these cellular genes, the cell fails to undergo apoptosis
Some adenoviruses cause cancer
Replication of viral DNA and late events
DNA replication occur in the nucleus
The L genes (“late”) are responsible for DNA replication and synthesis of structural proteins of the virus (e.g., capsid)
One RNA of the L region is transcribed, which is then processed into mRNAs for the polypeptides

6. Adenovirus Replication
Replication (cont.)
Viral assembly and maturation
Morphogenesis occurs in the nucleus
Capsomeres self-assemble into loose, empty capsids
An L protein inserts the DNA into the capsid
The left end of the viral DNA has a cis-element that is recognized by the L protein
The capsid compacts upon itself
It is inefficient
80% of the capsomeres are unused
90% of the DNA is not packaged
But 100,000 viruses can be produced by a single cell

7. Adenovirus Evasion Strategies
E3 region of genome encodes several anti-immunity proteins
gp19 binds to and prevents class I trafficking to the cell surface
It also binds to TAP and inhibits peptide translocation
10.4K and 14.5K proteins interfere with tumor necrosis factor-induced apoptosis

8. Virus Effects on Cells Marked CPE
Crystalization of viral capsid proteins in the nucleus
Useful for diagnostic purposes
Transformation