Hitchhiking through the nervous system

I while ago I wrote a post about how virus's get from the outside of the cell to the interior of the nucleus and found that virus particles are able to hitchhike on the cells internal transport systems. I was quite interested therefore to find a paper in Nature Reviews (reference below) that revealed that not only do virus's latch on to host proteins to travel around inside the cell, they also use host extracellular processes for travelling around the body. And outside the cell it's not just virus's either, bacterial toxins need transport systems too, unlike whole bacteria they can't move around under their own power.

One place that the body wants to protect particularly well against infection is the central nervous system. It provides this protection by surrounding it with a wall of tightly sealed endothelial cells known as the blood-brain barrier. However despite this the body itself still need to get some things into the CNS; small molecules such as glucose and oxygen as well as larger cells of the immune system. These immune system cells provide the first sneaky point of entry; virus's such as HIV can hitch a ride inside these cells and get into the central nervous system that way. This is the equivalent of hiding in a truck to avoid border patrols.

However some virus's and toxins use an even more sneaky method, dressing up as a border-patrol guard and simply walking in. Throughout the blood brain barrier there are long neuronal projections that connect the central nervous system to peripheral organs. A picture of one of these cells is shown below:

Like all cells, this contains the transport molecules Kinesin and Dynein, which virus's can latch onto in order to transport themselves through the cell (see earlier post here). Once they get inside the cell, the cell's own proteins will carry the virus particles all the way through it, and into the central nervous system. However first it has to get inside the cell, through the little blue blob at the bottom (in the diagram above it's highlighted with a little dotted square).

As well as receiving chemical signals for electrical impulses (that make the neuron function as a nerve) the blue blob also contains various different receptors capable of engulfing and uptaking small molecules, including those used to signal some neural impulses. This means that there are a range of chemical receptors on that blue blob which allow the uptake of molecules, and you can probably tell where this is headed...
The diagram above is the intramolecular equivalent of Han Solo dressed as a Stormtrooper wandering into the Death Star. By changing its outer coat enough to mimic the proteins that are usually taken up by the cell the Herpesvirus can attach to the outer membrane and then be absorbed into the cell. Once inside, it can latch onto the dynein and get a free pass all the way into the nucleus (and neurons are pretty long so it is a bit of a journey). Poliovirus and rabies can also carry out this trick (at the neuromuscular junction for anyone interested) along with the bacterial botulinum toxin, which gets taken up by synaptic vesicles and essentially kills the end of the nerve, which can either lead to instant death or a scarily smooth robot-plastic forehead, depending what context you take it.

I always find it quite spooky to think of my body in that way, as a huge maze of intracellular processes, being negotiated, infected and protected by tiny substances outside of my conscious control. I think that's another reason I find cellular biology so fascinating, by studying it we gain control (or if not control at least an understanding) of these detailed processes that we would not normally be able to influence.

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Salinas S, Schiavo G, & Kremer EJ (2010). A hitchhiker's guide to the nervous system: the complex journey of viruses and toxins. Nature reviews. Microbiology, 8 (9), 645-55 PMID: 20706281