SO SORRY I missed you for this show! I have just listened! I would have had great fun talking with you all about this RacPyV but I missed my chance. Thankfully you all did a great job. So very sorry I missed you.
Thanks for the feature!
Back at work, and just as a follow up for the conversation about raccoons:
1. Completely agreed about the proof needed for causality.
2. Dr. Imperiale helped us in this story by providing constructive feedback on our paper. He was very interested and it helped me to understand where the viral oncogenesis field stood on this. He was gracious about his doubt, just as he was in his comments about LT expression being scanty. Heavens it is that. But IHC is a pretty blunt tool, and we’re using a Merkel Cell polyclonal antibody that only vaguely maps to the RacPyV genome. Those are some possible reasons for the lack of robust signal. In the meantime-we’ve cloned LT into an expression vector so that we can use more robust antibodies in the future. The CT counts from our realtime PCR assay tell a different story. Numbers like 17-19 when we target LT in the tumors…I’ll get back to asking for his advice when we have an antibody in hand and something to talk about!
3. THE DOGMA. We, of course, thought that we could help ourselves to that end by doing Southerns to prove integration…which has become, since Merkel Cell Virus, somewhat of the dogma for causality. But, as you noted, RacPyV, at least the bulk of it, is unintegrated. There are more sensitive ways to assess integration at low levels, but I think we have to consider persistence in the absence of integration. That’s where we are. For me it’s just plain fun to consider it, and I could use a real virologist’s help (as long as they are not too dogmatic) in this. As a pathologist who is either 1. thinking outside of the box (because she is outside) or 2. unencumbered by facts (which I am) it seems like there are some possibilities here: take mitochondria. They have a circular (like PyV) genome, and regulate their replication, transcription, and translation completely independently of the nucleus. I look at ultrastructure all the time and many viruses are associated with mitochondria. Also, couldn’t we be dealing with low level replication, encumbered by something other than an integration/late gene deficiency deal? You’re the best at questioning dogma, what do you think?
4. The species jumping/end host possibility. We have found this virus in an opossum and a squirrel. We don’t know if it’s replicating there. Given that other PyVs can become replication deficient (and oncogenic) exactly BY jumping hosts, we thought this should be a consideration. We’re on it, and looking at humans and other mesopredators in the mix.
And from your friendly neighborhood veterinary pathologist: So much roadkill, so little time.
Anonymous anonymous writes:
I am a long-time fan of the show and am very grateful for what you do!
Quick question regarding your discussion of the Factor X adenovirus story– If factor X has evolved to combat some adenovirus species, does this mean that adenovirus (or some other virus with similar capsid properties) has exerted pressure on the germ line, such that those organisms that produce Factor X (that binds adenovirus capsid) have a selective advantage? Alternatively, could it not also be possible that some adenoviruses derive a benefit by binding to Factor X? Perhaps binding to Factor X allows entry into a beneficial cell type. Or perhaps binding to Factor X “slows down” the kinetics of infection thereby allowing for long-term advantages by promoting persistence. These alternative possibilities seem equally likely to me, since it seems the virus would have enough “evolution power” to evolve away from Factor X binding before the mammalian genome evolution could catch up. In general, it seems that authors have to “sell” the host defense side of these newly identified interactions that slow down replication, when it is just as likely (more likely?) that persistent viruses derive fitness benefits by allowing for an attenuated infection.
Again, keep up the good work and many thanks for being so selfless with your time!
Hi! Love all your shows.
I have a question regarding Janine Roberts if you have heard of her.
You can take a read at http://www.sparks-of-light.org/polio-cause.html.
I know you’re the king of polio so I’d love to hear your version of it!
Johan from Sweden
Dear TWiV team.
There are many cases of norovirus in the UK this winter, estimated at 100,000 cases over the Christmas period with the number of confirmed cases 72% higher than this time last year.
I have read that following a norovirus infection a person’s immunity only lasts for around 14 weeks.
I wondered if this is solely down to the rapid rate of mutation of the virus or does a person’s immunity to this type of virus decline rapidly over a short time.
Christiane Wobus replies:
Both, viral evolution and inability to raise long-term immunity are to blame. There are old papers from the 70s showing that human volunteers infected with exactly the same strain of virus will be re-infected after 1 year (but not if the interval is 14 weeks or less). So, short term immunity develops but not long-term immunity. Also, noroviruses show antigenic drift akin to what is seen with influenza. If you want, I can pull up those references.
Also, check out this entertaining read about noroviruses (which for a general news article is quite accurate). This might be a fun read for your listeners. 🙂
How not to catch the norovirus
Hope all is well and best wishes for a successful 2013, Christiane
Christiane Wobus, PhD
University of Michigan
Department of Microbiology and Immunology
The question of life seems to keep coming up. The existence of metabolism has been stated as significant difference, however metabolism can be viewed as a dynamic chemical kinetic problem in a system that isn’t in thermodynamic equilibrium. Other pure physical/chemical systems also appear life-like, such as various reaction/diffusion system, mineral growth system, etc.
See: http://www.youtube.com/watch?v=QJB1Jsk_oTE for an example of a very simple system with some interesting behavior.
PS: Still behind on twiv and twim, but slowly catching up.
I can’t thank you enough for the wonderful podcasts.
When I graduated from college I used to think that people who didn’t read the New York Times, the Wall Street Journal, or the like were hopelessly ignorant of the world around them.
Given the explosive growth in high-quality podcasts, such as yours, I now consider people who get their information primarily from the popular press to be the ignorant ones.
I also love Vince’s lectures on iTunes U.
Keep up the good work!
Waterloo, Ontario, Canada
Hi, my name’s Will. I have a question regarding the rabies virus. First of all, I heard that once the rabies virus enters the peripheral nerves it is sequestered from the immune system. is this true? and if so, how? I heard that the rabies virus is intracellular and neurotropic meaning it hides within neurons. Is it that antibodies created by the vaccine are not able to enter into neurons in order to kill the virus within? I’ve heard elsewhere that antibodies can enter cells in order to defeat the viruses within them, but I’ve read so much contradictory stuff elsewhere that I don’t who what is true. This seems like a pretty reputable blog. I was hoping you guys could set the record straight.
I know antibodies can enter neurons where the rabies viruses are hiding, but how do the antibodies know the viruses are in there? Is it just by chance that the antibodies enter the neurons and find the viruses? and also, I know it slows the spread of the virus in the CNS but what about in the peripheral nerves
Voodoo virology – how can Roche withhold its data?