It's been quite some time since I've written any posts here (not exactly true, I have about a dozen unfinished drafts of posts that I may get around to finishing eventually), so I thought I'd break the silence with the details of some interesting research on viruses recently published in Science1.
How viruses spread and infect new cells within the body is just as important as learning how viruses are spread from person to person (or from other animals to humans, as the case may be). There are lots of ways viruses can spread to new cells once a host has become infected, and some of them are pretty interesting. Some viruses churn out massive amounts of viral particles and cause the host cell to rupture, and the swarms of progeny will infect nearby healthy cells. A team of researchers in the UK, however, have discovered a new method of viral cell to cell transmission that's a bit...different: viral catapults.
The team from Imperial College London, lead by Geoffery Smith, fluorescently tagged vaccinia poxvirus and using live-imaging techniques, were able to visualize how vaccinia is able to move from cell to cell. What they found is pretty interesting.
Once a cell has been infected by vaccinia, the virus hijacks the cell's replication machinery and uses it to rapidly produce massive amounts of two particular viral proteins called A33 and A36. These two proteins are then transported to the cell's membrane and are expressed on the outer surface, forming a sort of mesh around the cell. This mesh acts kind of like a tag that tags the cell as having been infected. When another vaccinia virus comes along and contacts the cell, it isn't able to get inside because of the A33/A36 complex. Instead, the virus gets lodged in the mesh.
Now for the really cool part. Once the virus has become lodged in the protein complex, this triggers a cascade within the host cell that rearranges its actin microfillaments (microfillaments, composed of action, are a part of the cell's cytoskeleton, the network of fibers that allows cells to maintain their shape and structure, as well as playing a role in cellular locomotion, division and intracellular transportation). The fillaments are rearranged into one long fillament that protrudes out at the site of viral attachment and sends the virus flying off into the intercellular medium, hopefully to find an uninfected host cell far away from the site of infection. Think of it kinda like hitting a billiard ball with a cue and knocking it to the other end of the pool table.
Totally cool.
This explains some observations made by Smith and colleagues about the rate of infection of the vaccinia virus. Vaccinia is seemingly able to move through populations of cells at a faster rate than would be predicted by viral reproduction rates alone (they were able to film a short video of the virus spreading quickly through a culture of cells, too! It certainly does move fast.) This ability of vaccinia to catapult itself to new potential hosts provides an adequate explanation.
Smith and co. went even further with their research. They knocked out the genes for A33 and A36 from the virus and found that these mutant viruses had significantly increased infection times. Furthermore, they inserted the A33 and A36 genes into healthy human cells, and found that it was sufficient to induce the virus-flinging reaction. This suggests that the whole mechanism - reception of the viral docking into the complex, signaling to trigger the rearrangement of the actin filaments and recruitment of the filaments to the proper location - is mediated by only two proteins! The team is not sure how the two proteins are able to pull off this task, but I'll be keeping my eye out for more research from their lab to find out.
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1. Doceul, V., Hollinshead, M., van der Linden, L. & Smith, G. L. Science advance online publication doi:10.1126/science.1183173 (2010).
