Lecture 6 2/6/24 Flashcards
What is virus evolution?
-genomic changes in hereditary genomes that may result in phenotypic changes
-occurs within a viral population
Why is it important for mutation rate to be balanced?
-too high of a rate results in defective progeny
-too low of a rate does not allow progeny to adapt to changing environment
Why do RNA viruses tend to have more mutations than DNA viruses?
-higher error rates and lower stability
-viral polymerases lack proof-reading mechanisms
What are “hot spots”?
certain positions in viral genomes that have higher mutation rates
What are the characteristics of selection pressure?
-does not cause mutations
-selects for already existing mutants
What is a mutation?
change in the base sequence of a nucleic acid resulting in the alteration of the resulting protein
What happens when mutations occur in less tolerant proteins?
results in a non-infectious virus
What are the three types of drift/point mutations?
-silent
-substitution
-nonsense
What is a silent mutation?
mutation within a codon that produces the same viral protein sequence
What is a substitution mutation?
mutation within a codon that produces a different viral protein sequence
What is a nonsense mutation?
mutation within a codon that leads to the cessation of the viral protein sequence
What is a conservative substitution?
when a different amino acid is substituted, but it has similar properties to the original amino acid
What is a non-conservative substitution?
when a different amino acid is substituted that does not have similar properties to the original amino acid
What is a deletion mutation?
-deletion of nucleotides
-causes a frameshift mutation
-changes amino acid sequence downstream of mutation
What is an insertion mutation?
insertion of multiples of 3nt bases to a viral gene, resulting in the addition of amino acids
Which type of mutation is easy to revert back to wildtype?
point mutations
What is reassortment?
gene segments are mixed and matched when two different viruses strains end up in same host cell
What is recombination?
portions of gene segments are interchanged when two different virus strains are in the same host cell
What is antigenic drift?
-accumulation of small point mutations
-leads to minor antigenic changes with epidemic/seasonal potential
What is antigenic shift?
-viral reassortment of gene segments
-leads to major antigenic changes with pandemic potential
What are the characteristics of canine-parvovirus-2 evolving from feline panleukopenia virus?
-only 5 amino acid differences between the structural proteins
-these mutations provided CPV-2 with the ability to bind to the canine transferring receptor and infect dogs
What are the characteristics of feline enteric coronavirus and FIP?
-FECV is ubiquitous and causes mild enteric disease
-FIPV, a mutation of FECV, occurs in 10% of FECV cases and causes fatal systemic disease
-FIPV cannot be transmitted to other cats, but FIPV-infected cats can shed FECV
-FIPV is likely a mutant that undergoes autonomous infection
During which period of gestation can BVDV lead to a persistently infected fetus?
50-125 days of gestation
How does recombination play a role in BVDV?
-PI calves typically have non-cytopathic BVDV strains
-exposure of the PI calf to a cytopathic BVDV strain can lead to recombination between the two strains
-viral genome recombines with host mRNA, leading to expression of proteins that can be toxic
What is cancer?
when a cell becomes biologically abnormal due to a disruption in cellular transformation and growth
How do viruses subvert the cell cycle to their advantage?
-target specific steps in cycle to improve viral replication
-induce a G1-S phase transition to replicate their genome during cellular DNA synthesis
-induce a G2/M arrest to provide optimized environment for maximum viral replication levels
Which types of mutations from oncogenic viruses can cause cancer?
-gain of function mutations in proto-oncogenes
-loss of function mutations in tumor-suppressor genes
Which RNA tumor viruses are most important in vet med?
retroviruses
Which DNA tumor viruses are most important in vet med?
herpes and papilloma viruses
What are the three standard genes in a model retrovirus?
-Gag: structural proteins
-Pol: reverse transcriptase
-Env: envelope protein
What are the three main classes of transforming retroviruses?
-acute transducing viruses
-non-transducing viruses - chronic
-non-transducing viruses - long latency
What is an example of acutely transducing retroviruses?
feline sarcoma virus
What are the characteristics of acutely transducing retroviruses?
-highly oncogenic
-genome contains viral oncogene in place of one of the core genes
-oncogene is replication deficient and requires a helper retrovirus to provide missing core gene
-oncogene expression is controlled by the virus
-oncogenes originate via transduction of cellular proto-oncogenes when they insert proviral DNA during replication
What is an example of chronic non-transducing retroviruses?
feline leukemia virus
What are the characteristics of chronic non-transducing retroviruses?
-RNA genome of virus is reverse transcribed into DNA and integrated into host genome (provirus)
-when provirus integrates near a host cell’s oncogene, it can inappropriately activate the gene and cause transformation into cancer
-integration occurs at random spots
What is an example of long-latent non-transducing retroviruses?
bovine leukemia virus
What are the characteristics of long-latent non-transducing retroviruses?
-retroviral protein is responsible for cell transformation
-proteins do not appear to affect retroviral replication life cycle
-retroviral protein likely causes uncontrolled transcription of a host cell’s genes
What are the characteristics of DNA virus transformation?
-genes from DNA virus responsible for transformation are viral in origin
-transforming proteins interact with proto-oncogenes or inactivate tumor suppressors to induce transformation
What are the characteristics of Marek’s disease virus?
-transforms T cells into other cell types when undergoing latency, leading to uncontrolled proliferation
-disease is contagious
-preventable by vaccination
What are the characteristics of papillomaviridae and cancer?
-viruses cause benign, superficial tumors
-warts generally regress with age
-in some cases, warts can progress to malignancy
-UV light thought to act as a co-carcinogen
-autologous vaccines possible
