is Viruses
What a prophage? A. A phage genome that has integrated into the DNA of a bacterium * B. A phage genome, before it has integrated into the DNA of a bacterium C. a phage that is propelled out of an infected bacterium D. a phage in which the proteins begin with proline, rather than methionine E. a phage with a propensity toward the lysogenic cycle
Foot and mouth virus
Defining life is difficult Viruses straddle the boundary between the quick and the dead
Data: This infectious agent cannot be filtered or cultivated on media Conclusion: It is a new form, not bacterial. How convincing is this?
(Very) generalized life cycle of a virus
Lytic cycle of phage T4
L and lysogenic cycles of phage (lambda)
RNA Animal Viruses
Life cycle of an enveloped RNA virus
Draw the cycles on your own for all 3 virus types. Describe how new RNA and virus protein are made.
IV and V replicate RNA --> RNA Requires RNA-dependent RNA polymerase
RNA --> DNA Requires RNA-dependent DNA polymerase (reverse transcriptase) These are almost never host enzymes
*This reaction requires RNA-dependent RNA polymerase. Where does it come from and at what point is it synthesized? (Not actually shown in the diagram)
*This reaction requires RNA-dependent RNA polymerase. Where does it come from and at what point is it synthesized?
A
A
*B
C D E D C
*B
Since RNA synthesis happens right away, RNAdependent RNA polymerase has to be carried by the virus as it enters the cell. The first point it can be made for the new virus particles is at D. E
HIV reproductive cycle
The HIV virus is 9,800 nucleotides long (9.8 Kb). How many genes does it code for? A. B. C. D. E. 1 9 90 900 30,000
Why is a HIV vaccine so difficult to produce? The HIV virus is 9,800 nucleotides long (9.8 Kb). How many genes does it code for? A. B. C. D. E. 1 9* 90 900 30,000 Reverse transcriptase has limited proofreading function, so the mutation rate is high. Why were we able to get rid of smallpox? It is a dsDNA virus, with proofreading, and it has only one host
The average length of a protein is 300-400 amino acids. Lets say 400. So it needs a gene with 400 X 3 = 1200 nucleotides (since there are no introns in these genes). 9,800 nucleotides could code for about 9 genes.
Inhibiting HIV AZT is a structural analog of thymidine that cannot form the sugar-P backbone. It was developed inhibit to DNA polymerase as an anti-cancer drug but it has little effect However, it is 100X more effective against reverse transcriptase
Inhibiting HIV
Protease inhibitor the virus proteins are made as a long polypeptide and the viral protease clips them prior to virus assembly the protease active site was analyzed and compounds were made to fit (rational drug design) protease inhibitors are peptide mimics with non-peptide bonds cocktails reduce viral load to below detection limit why force the virus down that severely?
Azidothymidine
thymidine
Influenza: ssRNA (sense) H (15 types) and N (9 types) are proteins on surface antigenic drift: small, progressive changes antigenic shift: major reassortment pigs can get bird and humans strains together strains can then reassort in the pig 1918-1919 (H1N1) pandemic killed 20-40 M people around the world (600,000 in US) swept across the US in 7 days disappeared quickly also 1968-69 (H3N2) killed 34,000 in US 1997 (H5N1) Asia first direct bird-human transmission 2004 (H5N1; H7N3, H10N7) in various places 2009 H1N1 has genes from pigs, birds and humans seasonal flu is also circulating (H3N2 and others)
Tulip breaking virus
Virus-free tulip
Still Life, Maria Ossterwijck, 1669 During tulip mania in 17th century Netherlands, these tulips sold for fantastic prices. The virus weakens the plants, so it has been eliminated. Variegated tulips are now obtained by breeding.
Tulip mania Viroids: circular RNA molecules. Few hundred nucleotides The code for no proteins.
This is the first recorded economic bubble. According to popular opinion of the time, the price could not drop because there was an inexhaustible demand. When the bubble burst in 1637 it chilled the economy of the Netherlands. Sound familiar?
At the price peak a single Viceroy tulip bulb cost 3000 to 4200 florins. A skilled craftsman earned about 300 florins/year. Bulbs were bought and sold in a speculative futures market, with few bulbs actually changing hands.
Cadand-Cadang disease of cocunuts Potato Spindle Tuber Viroid
Prions
The End (stay healthy)
Normal prion protein
Mis-folded prion protein
Prions are implicated in mad cow disease and Creutzfeldt-Jakob disease in humans. Fungal prions do not cause disease. They may even be evolutionarily advantageous and carry a mis-folding, protein-based inheritance