Virology Flashcards
WHat are the two Virus theries?
Evidence for the RNA world theory?
Evidence for Reductionist theory?
RNA world theory
–Life arose with viruses
Reductionist theory
–Viruses came after cellular life; they are reduced versions of cellular organisms
RNA world evidence: Ribozyme- self replicating RNA
Reductionist evidence: Viruses have genes related to those of cellular genes, often pick up cellular genes
What are ribozymes?
RNAs that can catalyze specific reactions (similar to enzymes)
-They can even catalyze their own synthesis
Natural funcitons of ribsozymes?
3
- cleave RNA,
- viral replication,
- tRNA biosynthesis
DNA viruses start off how and end how?
3 Steps
Examples? 3
Start as DNA
then
Transcription to
RNA
then
Translation to
Protein
Ex: Herpes, Smallpox, Mimi
RNA viruses start off how and end how?
2 Steps
Examples? 3
Start as RNA
then
Translation
to
Protein
Examples: Rhino, influenza, SARS
Retroviruses start off how and end how?
4 Steps
Examples?1
Start as RNA
then
Reverse Transcription to
DNA
then
Transcription to RNA
then
Translation to
Protein
Examples: HIV
DNA viral genome Pros?
3
- Lower mutation rate
- More stable (can carry more genes)
- No dsRNA phase
DNA viral genome cons?
2
- Lower mutation rate
2. Slower replication
RNA viral genome pros?
2
- Fast replication rate
2. High mutation rate
RNA viral genome cons?
3
- High mutation rate
- Limited sequence space (less stable)
- dsRNA phase
Why is HIV so highly mutated even in one single infected body?
They are a retrovirus which means they have a reverse transcriptase step that is different from the orderof the central dogma. This step is also where all the mutations are occurring (1 mutation per virus).
What can’t HIV be cured by antiviral drugs?
It integrates into the cell (hides in it) so we cant get rid of it/recognize it
Challenges in developing vaccines?
7
- High mutation rate
- Integration into the host genome
- Infects immune privileged region of host
- Targets immune system
- Multiple serotypes
- Costs and time involved in development
- Vaccine safety concerns
When do the earliest synmtpoms of HIV appear?
Earliest symptoms appear at two weeks (if at all)
HIV mutation rate is what?
~1 base change per genome
25-30% in circulating HIV strains diveristy
What are the most dangerous mutations in viruses?
2
- Some allow a competitive advantage
- Some allow escape from antiviral drugs
Which retroviral proteins would you design drugs to target?
4
- integrase,
- reverse transcriptase
- Protease inhibitors
- Fusion entry inhibitors
Describe the nucleotide analong mechanism?
Which drugs are these?
2
nucleoside analog mechanism (prevents adding onto the chain-chain terminator)
-because its so faster for the virus it mostly gets sucked by that instead of our own DNA
NRTI- purine and pyrimidine analogs
3TC (Epivir/lamivudine) drug group?
MOA?
Reverse transcriptase inhibitor
-Nucleoside analog
(NRTI)
Cytidine mimic – acts as a chain terminator
DLV (Rescriptor/delavirdine) drug group?
MOA?
Reverse transcriptase inhibitor (non-nucleoside)
NNRTI
Binds RT catalytic site, blocking polymerase function
DRV (darunavir/Prezista) drug group?
MOA?
2
Protease inhibitor
- binds the active site preventing the processing of viral protein precursors
- Compete with the natural substrate
EVG (Elvitegravir) drug group?
MOA?
Allosteric integrase inhibitor
INTI
Prevents functional multimers from forming (dimer of dimers = tetramer)
MVC (Selzentry/maraviroc) drug group?
MOA?
Entry inhibitor/ CCR5 antagonist
Drug binds receptor (CCR5), preventing HIV from binding
Mutant binds receptor in a different conformation
T20 (Fuzeon/entuvirtide) drug group?
MOA?
HIV fusion inhibitor
Mimics viral protein to displace it in the fusion complex– binds gp41 and prevents formation of the entry pore
(prevents the virus from fusing with healthy T cells)
