Slanted Science

It’s a pandemic, but not – so far – a particularly deadly one. Health officials are still concerned, though, that the H1N1 influenza virus may acquire the right mutations during this initial period of infection to make it a much more formidable foe during the next year.

Which is why scientists are still working feverishly (forgive the pun) on finding out how the human body responds to H1N1 infection, and whether an individual’s chances of surviving it can be improved.

Their latest discovery is that a family of proteins called IFITMs contribute to resistance to H1N1, as well as West Nile and Dengue viruses.

The work was a collaborative effort between scientists from various institutions, lead by Stephen Elledge of Harvard’s Department of Genetics. The paper is available to download for free from the website of the journal Cell.
Here’s how they did it:

The boffins grew (‘cultured‘) human cells in their lab. (Quick note: this is actually surprisingly easy to do: put some cells into germ-free plastic dishes, add a liquid which provides nutrients, and keep at 37^oC. The cells will grow quite happily, just as though they were still in the body.)

They infected samples of these cells with one of three viruses: H1N1; West Nile; or Dengue. At the same time, they also dosed the infected cells with ‘small interfering RNA‘, or siRNA, which is a way of reducing the cellular levels of any single protein the scientists wish to study. After a period of incubation to allow the virus to replicate itself, they counted the percentage of human cells which became infected.

This whole process was repeated using many different siRNAs, allowing the researchers to look at the effects on infectivity of reducing levels of a variety of proteins. They were looking for cases in which knocking down a particular protein caused a decrease in the number of infected cells; this would indicate that influenza virus particles use the protein to propagate itself.

The group found over 120 proteins which seemed to assist the virus in propagation. However, their experiments also unearthed a family of proteins which work in the opposite way: loss of these proteins led to an increase in viral infection, indicating that their role is in defending the body against viruses.

It is not yet clear how this family of proteins (IFTMs 1-3) acts to inhibit viral entry into cells. However, their location (spanning cell membranes) and other data leads Elledge to speculate that the proteins direct virus particles which enter a cell towards an area where they can be safely broken up and disposed of. This would explain why the proteins are not normally expressed at significant levels (they would likely begin directing essential cellular components for destruction), and may limit their future usefulness as therapeutic targets. Elledge notes the unknowns:

Making too much of these proteins might not be good for people in the long run, but we don’t really know yet.

Don’t Hold Your Breath, But This May Lead To: if not a way of boosting the human immune system during pandemics, then perhaps a broad-spectrum antiviral treatment for farmed animals, where diseases are common.

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