Lecture 6 - Features of viral genomes Flashcards
What are the features of viral genomes?
- can be DNA or RNA
- can be single or double stranded
- genome smaller than host cell
- range between 5000 and 23, 000 bp
Why are virus genomes so small?
Under a size pressure
- Genomes of viruses that infect prokaryotic cells are compact (have overlapping genes) in achieve maximum genetic capacity - they need to replicate fast to keep up with their hosts
- Genomes of viruses that infect eukaryotic cells are also under pressure, they have to fit into the virion - limit is packagin size
What is the difference in size in RNA and DNA genomes?
RNA viral genomes are typically smaller than DNA viruses because:
- RNA is fragile, so long strands can easily break. The biochemical structure means that it is more sensititvve to hydrolysis and therefore unstable.
- RNA genomes have in general higher mutation rates than DNA genomes
Are viral genome mutations benefitical or detremental?
Mutation is a mixed blessing
- beneficial because mutations may allow an escape from immune system and increased fitness
- but deleterious mutations can limit viral replication and spread
Have to be combined with other features to be a positive feature
What are the typical rates of viral genome mutation?
Range from: 1nt/1000-10,000nt in retroviruses; to 1nt/10,000,000,000nt in herpes virus (similar to eukaryotic DNA replication)
Why do RNA genomes mutate more frequently than DNA genomes?
RNA-dependent RNA polymerases have higher error rates than DNA-dependent DNA polymerases (these can sometimes be from the host)
- How many mutations per genome are there if a HIV genome is 9.7kb and the mutation rate is 1nt/1000-10000nt?
- How can the possibility of deterimental mutations be overcome?
- Everytime have a replication cycle, get between 1-10 mutations.
Very quickly a lot of mutations build up (as many viruses per cell), therefore within an infected person, there are lots of different vairants of HIV (Quasispecies)
- Has to be able to replicate quickly, if is slow, a bad round of replication may wipe out a lot of viruses. Combination of quick repication and high mutation rate = success
What are the different types of viral gene products?
- Structural proteins (formation of the capsid and envelope)
- Enzymes (RNA/DNA polymerases, proteases, integrases)
- Regulators of viral gene expression
- Regulators of host gene expression
Some are more sensitive to mutation than others e.g. mutation in the catalyctic site of an enzyme = bad
When do genetic interactions between viruses occur?
During superinfection (infection of one cell with more than one mutant)
Define viral complementation
Interaction of viral gene products of two viruses that result in increased production of one or both of these viruses (e.g. one virus provides a gene that is defective in the other virus)
Both viruses remain unchanged genetically.
Define viral recombination during superinfection
Physical interaction between enomes resulting in genes that were not present in either parent virus. Joining of parts os the genome from different viruses.
Intramolecular (homologous or non-homologous) recombination or reassortment (viruses with segmented genomes)
Why do herpes viruses exists of a mixture of 4 isotypes?
Herpes virus genomes have a unique long (UL) and unique short sequence (US) region bounded by inverted repeats. These repeats allow rearrangments of the unique regions and Herpesviruses therefore exist as a mix of four isomers (HSV: 150kbp; V2V: 120-130kbp; CMV: 220kbp; EBV: 170 kbp)
What are the features of herpes virus genomes?
- Genomes are tethered (not integrated) to the host chromatin, often in circular episomes
- Genomic clustering of genes expressed in different lifecycle stages (Latent vs. Lytic)
- Major latency genes mediate viral genome tethering (only require genes required during latency)
- Lytic transactivator genes initiate the cycle leading to virion production
- Latency genes often inhibit lytic transactivation
- Frequently encode for cellular homolog genes
How is most dsDNA viral genomes found in the cell? (structure)
- Mostly found circularised. Have clustered genes, genes expressed in one section are all the genes expressed during a particular part of the virus life cycle.
- contain cellular genes stolen from the host cell (cellular homologues): vFLIP, vCYCLIN, vOX2, vGPCR, VIL6, vMIR1/2, vCCL2/3, vIAP, vBCL2
- KSHV episome contains laten cluster (polycistronic) and a lytic activator (ORF50)
What is the lytic transctivator as part of the dsDNA viral genome?
RTA or ORF50
inhibited by LANA(major multifunctional latency protein that tethers the episome)
Why do dsDNA viruses have cellular homologues? (KSHV episome)
Have low mutation rates so must find other ways to interact with the host cell
What are the features of ssDNA genomes?
- Commonly (but not always) circular
- Genome: 2 - 30kb, encoding for 4-15 ORFs (with some exceptions)
e.g. M13 filamentous bacteriophage
Describe the genome organisation of M13 filamentous bacteriophage as an example of a ssDNA virus
Host RNA and DNA polymerases convert the +ve ssDNA viral genome into a covelently closed dsDNA called the replicative form of DNA (RF) [intermediate essential for replication and transcription)
Viral g2p protein nicks RF DNA strand at the origin of replication. +ve strand replication occurs. New +ve ssDNA genomes are converted into new RF molecules and further transcription occurs.
When enough g5p protein is synthesised, conversion into RF dsDNA is inhibited as newly synthesised genomic ssDNA is covered with g5p. g5p is replaced by g8p to trigger the assembly into the viral capsid.
