29 January 2016

Rabid Alaskan foxes

Karsten Hueffer was on our campus yesterday, giving an interesting talk on the biology of rabies in Alaska. And yes, whenever someone from Alaska comes to Teas, there were a few pointed jokes about the relative size of the two states.

Rabies is one of those diseases that almost everybody knows about, but not very many people actually experience it, either directly or indirectly. (Well, in North America, anyway: about 50,000 people worldwide die of rabies annually.) The pathology of rabies is still not understood: the brains of people who die from rabies are not dramatically different from those of people who don’t have rabies. almost 100% mortality for people who are infected.

Rabies in Alaska is a big problem, and is primarily spread by foxes. Most cases of rabies occur along the Alaskan coast, where arctic foxes predominate. Red fox dominate central Alaska. Hueffer hypothesized that Arctic foxes are main rabies reservoir, and red foxes are just spillover hosts. He tested this by examining the three different strains of rabies, and looking at the population structure of the arctic foxes. It turned out there were three populations of Arctic foxes, and they all lined up very well with the three rabies strains.

Hueffer went on to do some species distribution models of rabies, to answer why is there no significant rabies problems in central Alaska? The models predicted rabies distribution well, but was also good at predicting the occasional outbreaks that occur sporadically in central Alaska. The species distribution models also predicted that the rabies will retract in the future, due to climate change.

Hueffer then switched gears to look at how rabies affects its host mammals. Normally, lethal infections doesn’t spread well, because the hosts are killed before the infection spreads. Rabies is able to beat this problem, in part, by manipulating their hosts into biting other animals. One protein in the rabies virus binds to nicotonic acetylcholine receptors, which are surprisingly similar to snake bungarotoxins.

In collaboration with molecular biologists, Hueffer and colleagues were able to create a toxin that was derived from the rabies protein (basically, a portion of the whole protein, if I understood right). From an experimental point of view, this is convenient because you can study the effects of rabies on nervous systems with none of the normal immune responses, and so on, that are triggered by infections.

They were able to show in a disk that this toxin interacted with acetycholine receptors. They then moved to testing their toxin in Caenorhabditis elegans (a.k.a. “a worm model”), and the rabies-derived peptide blocked normal feeding in their worms.

When this rabies-derived peptide was put in mice, the effect on behaviour was dramatic. The infected mouse kept running around its cage, up to ten times more than control mice. This strongly suggests that the virus is manipulating its host by directly interacting with neuronal receptors. While many viruses bind to cell receptors, usually they are doing do to trick the cell into bringing the some part of the virus into the cell. Rabies does not get into the neurons at all.

The entire rabies virus consists of just five genes. Rabies appear to be a particularly nice, simple model for behavioral manipulation by infectious agents.

External links

Karsten Hueffer’s faculty page
Karsten Hueffer on Google Scholar

Fox photo by Ralf Κλενγελ on Flickr; used under a Creative Commons license.

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