MCM 2-6 Viral Genetics Flashcards
Features that make viral genomes more efficient than eukaryotic or prokaryotic genomes
- genome is 100% coding DNA
- reading frames can overlap on a single strand or between a strand and its complimentary strand (different reading frame = different protein made)
- ribosomal frameshifting/slipping (translational frameshifting) changes the read amino acid sequence
- viral mRNA can be alternatively spliced (these proteases are targets for antivirals)
- expression of polyproteins (one long polypeptide is cut to form different proteins) makes once promoter enough for whole proteome
why is the mutation rate high in viral genomes?
- viral polymerases have high error rates. Very simple, tend to makes mistakes when creating nucleic acids
- no proofreading mechanism
- some viruses lack a complementary strand to pair with (cannot detect incorrect bases)
effects of viral genome mutations
a. Allow for epidemiological studies (MERS) - by counting mutations, can isolate and follow the mutations. See where a virus came from. Viral mutatons happen at predictable frequency, allows us to track that MERS had a common ancestor.
b. Allow for production of new viral antigens which avoid immunity (genetic drift of influenza). Lead to drug resistance (protease of Hep C) - produces new antigens from generation to generation. Old antibodies useless. This is why you need a new flu shot with new strain every year.
c. Inegration of viral genome into human DNA can cause cancer (papilloma virus in cervical cancer)
d. allowed production of early live vaccines - You can make a live vaccine by growing viruses in other animals. Mutations that increased host-range occurred. Use viruses that only infect the other animals. Adapt the virus to one species and use as vaccine in another species.
two viruses can simultaneously infect the same cell. Is this common? why or why not?
This is rare due to viral interference due to blocking of receptors, competition for resources, and stimulation of innate immunity
complementation
When one virus has a defective gene, another virus has a different defective gene, and both defects make the individual viruses unable to produce progeny. The two viruses complement each other by providing the protein that is defective or missing in the other, allowing them to both produce progeny. The progeny are genetically identical to the parents. Viruses need to be very similar to each other to “complement” e/o…like hep B and D
phenotypic mixing
two viruses with distinct proteins on their capsids infect a cell simultaneously. Progeny from both can have either the normal proteins, the proteins of the other virus, or a mixture of both…the mixture of both is called pseudotype (the genetic material of one virus in the capsid or envelope of another). The virions produced by these progeny will have the same protein structure as the initial parent virions and NOT the pseudotype…the “new” virus only lasts one generation….again the 2 viruses that “combine” must be similar to one another to do this
the mixed virus can not create progeny
recombination
When two viruses infect a cell simultaneously, and their nucleic acids undergo recombination. Some progeny will have recombinant genomes as a result. This produces progeny that are genetically different than the parents. This is the same as in any other organism
they will crossover and exchange genetic material
resortment
the most important mechanism
When two segmented genome viruses infect a cell simultaneously. The progeny will have different combinations of nucleic acid segments from both viruses. Only happens in viruses with a segmented genome. This produces progeny that are genetically different than the parents…brand new viruses that are stable…example: influenza
compare/contrast complementation, phenotypic mixing, recombination, and resortment in terms of genome change and progeny
Complementation and Phenotypic Mixing
- genomes of the parents are unchanged
- progeny will have the same phenotype as parental strains…
- A new replicating strain of virus is NOT produced.
Recombination and Reassortment,
genomes are changed
new strains of viruses are produced.
explain how viruses can be used for gene therapy
When viruses are used as vectors, one of their essential genes is removed, and that gene is inserted into a cell (complementation). Then a therapeutic human gene of interest is cloned into the virus, and the virus is grown in the cell. Several gene therapies have been successful in animal models so far; some human trials are now in progress.
problems with viral gene therapy?
§ Transient expression of foreign gene – In humans, even if the viral vector is successful in delivering the gene, the gene will be expressed initially only to fade within hours or days. The reason is unknown.
§ Requirement for very high doses of virus vectors
§ Inflammatory response to virus vector – The viruses are still antigenic, so they elicit an immune response.
These problems have had fatal results in some clinical trials.
viral genomes are ______, bacterial genomes are _____
eukaryotic, prokaryotic
gene expression in viruses is regulated by….
this helps explain the phenomenon of..
cellular transcription factors
tissue specificity - papillomavirus expression is regulated by keratinocyte proteins (has a keratinocyte enhancer site)
-Hep B gene expression is regulated by liver proteins (has a liver enhancer site)
modified viruses that replicate appear by…
mutations, recombinations, and reassortements
viral genomes are (2)
small and efficient
