Monday, January 14, 2008

ERVs and Infectious Disease!

One of the fun things about being a graduate student is the presentations by visiting PIs. Someone who is a researcher in California or Maryland flies in to give a presentation on their research. Unfortunately, my department is mostly made up of immunologists and bacteria folk, and I cant say those are the most interesting topics for me.


This semester Bossman was in charge of scheduling speakers, so a ton of them are virologists! YAAAY!! Todays speaker, Jackie Dudley.

If you dont know who she is, the first thing you should know is that she is one of the professors who signed a letter supporting Chris Comer.

The second thing you should know is that shes going to be on the Journal of Virology editorial board in 2009.

Third thing you should know is that she kicks ass!!! Personality wise, shes one of my new role models-- we got into a tiny tiff about the place of viruses in the evolution of life and the tree of life, but it was a FUN tiff! I coulda tiffed for hours! She was a lot of fun in the meeting with graduate students... at least for us virology grad students :)

Shes also done some cool research on the place of ERVs in the pathogenesis of disease. Remember MMTV? Pups get infected with exogenous MMTV when they are pups, and it activates every time a mouse starts lactating. After a few rounds of pregnancy, the female mouse gets mouse breast cancer. The virus doesnt *want* to cause cancer, it just happens.

Dudley wondered what part, if any, endogenous MMTVs played in this game. She made some mice that only expressed endogenous MMTV 6, 8, or 9, and another strain that had no endogenous MMTVs. She found that carrying an endogenous MMTV left the mice more susceptible to exogenous MMTV infection! No endogenous MMTVs? Only 10% of the mice progressed to tumors, as opposed to 90%-100% in the wild type mice. The mice that had one of the other endogenous MMTVs fell in between those percentages.

So having endogenous MMTVs are a detriment to the mouse!

... Or are they?

A colleague down the hall studied cholera, a gram negative bacteria. Now because of the way MMTV works (it codes a protein called 'Super Antigen'), some of the mouses T-cells get knocked out while it is maturing. Non-self MMTV proteins are recognized as 'self', so the T-cells that recognize these 'super antigens' coded by the endogenous MMTVs are killed, just like the T-cells that recognize a protein made by a lung cell or a liver cell. You dont want your immune system attacking you :) So, what happens when branches of T-cells are knocked out because of endogenous MMTV when you infect it with an unrelated organism?

Same thing.

Mice without endogenous MMTVs were not as susceptible to cholera.


Well, dont get too excited-- theyve tried other gram negative bacteria and other organisms, and they dont see this effect. But still! Some of these endogenous MMTVs only encode for the super antigen-- why are these kept, evolutionarily, if everything else is degraded??

Avenues for further research :)


jfatz said...

"I coulda tiffed for hours!"

What, no "wink-wink, nudge-nudge?" ;-)

daedalus2u said...

It might be to protect certain commensal bacteria from attack by the immune system.