Adenovirus Flashcards
What is the structure of the adenovirus?
These are naked DNA viruses that have an icosahedral capsid.
How do they enter cells?
These viruses do not have an envelope and are taken up by receptor mediated endocytosis. They have a penton fibre that engages with the cell adenovirus receptors on the surface (CAR). Once the endosome has been acidified and the penton base is released to burst the endosome, their capsid is released and is able to migrate to the nucleus where the genome is then released.
How do they solve the end-replication problem due to being DNA viruses?
Use of a protein primer. The end problem is solved by these terminal proteins that bind at the 5’ end and the origins of replication are at the ends of the genome. The genome binds this protein and it is packaged into the virion as it is covalently bound at the terminus of the nucleic acid. It recruits the viral polymerase and using the protein as a primer, it assists in replicating a leading strand in either direction to produce new copies of viral DNA (without a lagging strand). Replication is achieved through a pan-handle formation and requires new expression of early viral proteins pTP and Pol and cellular proteins.
What is the structure of their genomes?
Adenovirus has dsDNA, is naked, has terminal proteins and open reading frames. It has many early genes such as EIA, EIB and E3 as well as a series of late genes that are the structural proteins.
Discuss adenovirus replication.
The early genes are transcribed by cell RNA pol II from the DNA sequence and are alternatively spliced. The early proteins, including EIA are translated and then extensively phosphorylated. EIA is imported back into the nucleus where it increases the transcription of viral and cellular genes. EIA then turns on IE (immediate early). The presence of the viral protein (EIA) that is translated from the early transcripts initiates early gene expression (E). The protein E2 assists in driving replication of the DNA and the DNA accumulates at a sufficiently high level to undergo this process of anti-repression relieving promoter occlusion. This turns on the expression of the late structural proteins.
What is the importance of the packaging signals?
This is important for packaging the new viral DNA into new infectious particles and they overlap the enhancer region. The enhancer sequences are those that interact with cellular transcription factors and these promote the expression of the genes.
- Packaging signal is near the left inverted repeat and origin
- The signal is complex as they are a set of repeated sequences that overlap with enhancers that stimulate transcription
- The structure is recognised by the viral protein IV2a (also a transcription factor)
Discuss the assembly of virion structural units from virus proteins.
The Adenovirus monomeric proteins that assemble into the penton units first assemble as homo-multimers (penton base protein III) that are then assembled into a complex unit known as a penton.
The hexon units are made up of trimers of protein II and these are assembled with the assistance of a viral chaperone protein L4. The L4 chaperone protein does not become part of the virion, but new virus particles cannot form without it.
