I joined Marc Pelletier on 
episode 56 of Futures in Biotech for a conversation with Stanford University School of Medicine Professor Karla Kirkegaard. We talked about RNA viruses – where they came from, where they are going, and Dr. Kirkegaard’s unique approach to discovering antiviral drugs. Don’t miss this episode: Dr. Kirkegaard is a brilliant and eloquent virologist who makes complicated science easy to understand.
Video courtesy of Team ODTV
Download video (114 MB .mp4)
This was a really cool show. I have a few questions, though these probably reflect my lack of knowledge more than anything else:
If I understood correctly, Dr Kirkegaard wants to use drugs to target bits of the virus' life cycle in which a mutant resistant virus which is inside a cell alongside one or more susceptible viruses won't be able to complete its life cycle. That is, the susceptible viruses will actively interfere with the resistant virus, keeping it from reproducing and replacing the susceptible strains.
Now, she was specifically thinking about the subunits used to construct the capsid. If some drug caused susceptible viruses to produce messed-up subunits, then maybe the resistant virus couldn't manage to ever build a proper capsid and get out to infect other cells. But don't viruses mutate in ways that change their capsids a bit pretty regularly? If the virus isn't enveloped, doesn't it have to do this to adapt to a population of currently-immune hosts with antibody that sticks to the old strain's envelope? (I'm thinking of something like rhinovirus, which has enough strains to keep infecting adults even after we've had 100+ colds in our lives.) That seems like it suggests that mutant viruses can sometimes successfully change their capsids (by a mutation in the subunits, right?) despite the interference of all the other older viruses infecting the same cell.
My second question is about the idea of making proteins that are actively unhelpful, instead of simply ineffective. When I heard you guys talking about this, my first thought was about prions. Are there any prions known to affect viruses? (Maybe that high mutation rate means that all the viruses whose critical proteins have some alternative folding that messes them up have been selected out?)
This was a really cool show. I have a few questions, though these probably reflect my lack of knowledge more than anything else:
If I understood correctly, Dr Kirkegaard wants to use drugs to target bits of the virus' life cycle in which a mutant resistant virus which is inside a cell alongside one or more susceptible viruses won't be able to complete its life cycle. That is, the susceptible viruses will actively interfere with the resistant virus, keeping it from reproducing and replacing the susceptible strains.
Now, she was specifically thinking about the subunits used to construct the capsid. If some drug caused susceptible viruses to produce messed-up subunits, then maybe the resistant virus couldn't manage to ever build a proper capsid and get out to infect other cells. But don't viruses mutate in ways that change their capsids a bit pretty regularly? If the virus isn't enveloped, doesn't it have to do this to adapt to a population of currently-immune hosts with antibody that sticks to the old strain's envelope? (I'm thinking of something like rhinovirus, which has enough strains to keep infecting adults even after we've had 100+ colds in our lives.) That seems like it suggests that mutant viruses can sometimes successfully change their capsids (by a mutation in the subunits, right?) despite the interference of all the other older viruses infecting the same cell.
My second question is about the idea of making proteins that are actively unhelpful, instead of simply ineffective. When I heard you guys talking about this, my first thought was about prions. Are there any prions known to affect viruses? (Maybe that high mutation rate means that all the viruses whose critical proteins have some alternative folding that messes them up have been selected out?)