2-19 Viral Genetics Flashcards
How do viruses encode their genomes?
- DNA or RNA but not both
- Single- or double-stranded
- Linear or circular
- One segment or multiple segments
Viruses have from 2 genes (as in parvoviruses) to 200 genes (as in pox viruses). This is too few for independent survival, and viruses depend on cellular genes to supply the missing functions.
How do viruses express genes?
As with bacteria or humans: genes = enhancer/promoter region + ribosomal entry site + open reading frame.
UNLIKE bacteria:
- No operons
- Expression is not induced by interaction between an operator and a repressor/inducer, but by binding of cellular transcription factors to promoter regions (thus, viruses are eukaryotic)
What kinds of viral genome structures are there?
- Simple genomes: Genes in a linear arrangement on one RNA strand, with only a single promoter (e.g., retroviruses)
- Complex genomes: Genes on both strands of DNA, often overlapping, and each with its own promoter (e.g., adenoviruses, herpesviruses, poxviruses)
How do viruses compress their functions into minimal space for maximal efficiency?
- No non-coding regions
- Overlapping reading frames
- Translational frameshifts
- Splices
- Polyproteins, which are cleaved into individual proteins by specific proteases, which makes 1 promoter enough for an entire virus. (These proteases are unique to viruses and, therefore, potential drug targets, especially for HIV and hepatitis C.)
How common is viral mutation, and why?
Mutation frequency is high:
- High error rate of polymerase
- Lack of proofreading and error correction
- Lack of second strand in some viruses
- Small amount of genetic material, with no “waste”
DNA viruses are fairly stable, while RNA viruses are very unstable (1 mutation per generation).
Why are mutations important in viruses?
- Allow epidemiological studies (e.g., MERS)
- Allow live vaccines to be made (e.g., early polio vaccine; some mutations only allow a virus to grow under certain conditions)
- Can produce new antigens which avoid immunity (e.g. influenza antigenic drift)
- Can lead to drug resistance (e.g., protease of Hepatitis C)
- Integration of viral genome can cause disease (e.g., papillomavirus in cervical cancer)
What can happen if two viruses infect one cell?
The infection of 2 viruses in 1 cell is uncommon, because one will usually preclude the other, but when it happens, 1 of 4 things may follow:
- Complementation of 2 defective viruses: neither can produce progeny virus alone, but together they can produce viable progeny virus A and viable progeny virus B
- Phenotypic mixing of similar viruses: 2 very similar viruses will produce progeny for virus A and B, but also some pseudotypes via exchange of capsid proteins (virus A w/ B characteristics, virus B w/ A characteristics), which only last 1 generation
- Recombination of homologous viruses: 2 homologues enter a cell and cross over during replication, producing progeny different from parents
- Reassortment of segmented viral genomes: 2 segmented viruses mix segments, producing progeny different from parents
Why are most cells/organisms only infected with one virus at a time (i.e., why is viral interaction rare)?
- Blocking of receptors
- Competition for resources
- Stimulation of innate immunity
How would viruses be used in gene therapy?
- Delete an essential gene from virus
- Insert that gene into ‘complementing’ cell
- Clone the therapeutic human gene into virus
- Grow the virus in the complementing cell
- Test virus in cells, animals, humans
Diseases that might be treated by gene therapy are mainly those with a congenital lack of a single gene/protein (e.g., CF, combined immunodeficiency, hemophilia, various liver enzyme-deficiency disorders).
Delivery of gene therapy by viruses involves host-range mutants, which can be made from retroviruses, adenoviruses, herpes simplex virus, and adeno-associated virus.
What are some problems associated with viral gene therapy?
- Short duration of expression
- Very high doses of viral vectors required (low efficiency of gene transfer)
- Severe inflammation in response to the virus
- Insertion of viruses into a recipient’s genome leading to malignant disease
