Viral Genetics Flashcards
types of virus genomes
- DNA or RNA
- RNA pos or neg sense
- ss or ds
- segmented or non-segmented (RNA)
- linear or circular
- from 2-200 genes
- depend on cellular genes
parvo
-2 genes
retro
3 genes
papillomaviruses
8 genes
adeno
10 genes
herpes
70 genes
prokaryotic vs eukaryotic
- enhancer/promotor and operator and multiple open reading frames vs
- enhancer/promotor and cellular TFs, only one open reading frame
- viruses are eukaryotic
virus genomes are efficient
- no space wasted
- reading frames can overlap
- ribosomal frame shifting-gets caught in loop and moves over one and starts again
- alternative splicing of RNA
- cleaving of polyproteins by viral proteases
polyproteins
-targets for drugs
virus mutations
- mutant frequency is high because of high error rate of pol
- lack of proofreading and error correction
- lack of second strand in some viruses
- point, deletions, insertions, recombinations/rearrangements, insertion into host cell genome
- DNA more stable, RNA 1 mutation per generation
virus mutations 2
- allow epidemiological studies
- can allow live vaccines to be made
- can produce new antigens which avoid immunity
- can lead to drug resistance
- integration of viral genome can cause disease
conditional lethal mutations
- only allow a virus to grow under certain conditions
- temp sensitive mutants of flu
- host range mutants of polio, measles
antigenic variants
- produce new strains spontaneously over time
- antigenic drift
drug resistant mutants
- appear in response to some antiviral drugs
- acyclovir resistant herpes
- protease inhibitor resistant HIV
- amantidine resistance of flu
complementation
- one gene works in one virus and the other in the other
- when together, can use genes to make new viruses
- progeny are same as parents and will need complement to grow in new cell
phenotypic mixing of similar viruses
- exchange of capsid proteins
- make pseudotypes-genetic material of one virus with the capsid of another
- progeny still the same as parents
recombination of homologous viruses
- the exchange of genes by crossing over at regions of homology
- progeny are different from parents
- hybrid virus reproduces
reassortment
- rearrangement of parts or a segmented genome to form a new set of segments
- antigenic shift-makes new subtype-flu
interference
- infection of one virus tends to prevent infection by another by:
- blocking receptors
- competition for resources
- production of interferon or other antiviral agents
insertion mutations
-RT viruses insert into genome and cause mutation
gene therapy
- deletion of essential gene and insert that gene into packaging cell
- grow virus in presence of packaging cell-virus isn’t virulent but can still grow
- clone the therapeutic gene into the virus
- test in cells, then animals, then humans
monogenic disorders that may be treated
- hemophiia
- immune deficiencies
- retinal disorders
- liver enzyme deficiencies
- CF
approaches to cancer
tumor suppressor, silence oncogenes, immune response genes, toxic or suicide genes, replicating cytotoxic viruses
problem with replicating in human
-doesn’t spread beyond needle track because its made to grow with essential gene in cell culture doesn’t have essential gene
gene therapy vectors
- retroviruses
- adenoviruses
- herpes
- adeno associated
problems with gene therapy
- short duration of expression
- low efficiency of gene transfer
- inflammation in response to virus
- potential for chromosomal disturbances by virus-leukemia
future research will yield
- mutated viruses that cause less inflammation
- viruses that target a specific tissue
- conditionally replicating viruses
- non-viral methods of transfer of genes
