Virus Genetics Flashcards
How many copies of each gene?
Just one, too few for independent survival, depend on cellular genes to supply missing functions
Viral genomes types
DNA or RNA
Single or double stranded
Linear or circular
One segment or multiple segments
Gene expression
Genes are eukaryotic
Expression induced by binding of transcription factors to promoter regions
TFs are tissue specific
Viral genomes are efficient because they compress their functions into minimal space through:
No non coding regions Overlapping reading frames Translational frame shifts (ribosomes) Alternative splicing Poly proteins (cleaved into smaller proteins by specific proteases) *proteases are potential drug targets
DNA vs RNA viruses
Stable and unstable
Mutations can be:
Point mutations Deletions Insertions (rare) Recombination/rearrangement Integrate into host genome
High mutation because…
High error rate of polymerase
Lack of proof reading/error correction
Lack of second strand in some viruses
Mutations allow…
Epidemiological studies (MERS)
Live vaccines to be made (early polio)
Antigenic variants can avoid immunity (influenza)
Drug-resistant mutants
Integration of viral genome can cause disease (HPV)
Virus interactions
Genome not changed, progeny reverts to original phenotype:
Complementation-gene function of one virus replaces a mutated or missing gene of another and allows defective virus to grow
Phenotypic mixing-exchange of capsid proteins (mixture)
*pseudotype-genetic material of one virus in capsid/envelope of another
Genomes change, new strains produced:
Recombination-exchange of genes by crossing over at regions of homology->hybrid virus
Reassortment-rearrangement of parts of a segmented genomes to form new set of segments->rapid antigenic shift
Interference
Infection by one virus tends to prevent infection by another by
Blocking receptors
Competition for resources
Production of interferon or other anti-viral agents
Gene therapy
Aims to correct or prevent disease by transfer of appropriate genes to patient (usually with congenial lack of a single gene)
Delete essential gene from host range mutant virus, grow in complementing cell, clone therapeutic human gene into virus, grow, test virus in different animals and humans
Problems with gene therapy
Short duration of expression of foreign gene
low efficiency of gene transfer (need high dose)
Inflammation response to virus vector
insertions of viruses unto a recipient’s genome leading to malignant disease
Gene therapy for hemophilia
Correction of clotting time via transfer of factor viii in AAV vector