Adenoviruses Chapter 32

Properties of Adenoviruses Structure Icosahedral 70-90 nm diameter Double-stranded DNA, 26-45 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)

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

Adenovirus Replication

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

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

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

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