One drug to prevent all forms of 'flu

17 August 2015

Interview with

Dr Jacob Yount, Ohio State University

Worldwide, the flu kills up to half a million people every year. One of the main ways of
Ill woman with tissue preventing the disease is vaccination, but because the influenza virus is constantly changing or mutating, vaccine-makers are always playing catch-up. Now scientists may have a new way to fight the flu using a treatment that can prevent infection with any strain of the virus. Jacob Yount, from Ohio State University, has discovered how to boost the activity of a substance made naturally by our cells, called IFITM3, which has a powerful flu-blocking effect, as he explained to Chris Smith...

Jacob - What we've discovered is a way to enhance a natural antiviral defence mechanism in cells that is active against influenza virus. This involves a protein called IFITM3 (interferon inducible transmembrane 3). What IFITM3 does is it blocks the ability of influenza to enter cells. This is really a very ancient or primitive defence mechanism. It's present in some single-celled organisms and this is completely independent of vaccines or the antibody response that we're associating with vaccines.

Chris - What does that IFITM3 protein normally do on the surface of the cell then to block flu and stop it in its tracks?

Jacob - Exactly how IFITM3 is able to prevent the virus fusing with the cell is not entirely clear, but what we do know is that when cells make a lot of IFITM3, it becomes very difficult for the virus to infect cells.

Chris - Well, that begs the obvious question then, why don't cells make lots of it all the time?

Jacob - It's not entirely obvious why they don't make a lot of it, but what we know is that they don't keep it around until there's a virus present. So, once there is a virus infection then the cells, the body stars making a lot of IFITM3. And so, what that does is it limits the spread of the infection.

Chris - By literally stopping the flu getting into any new victim cells so it can't increase its numbers any further.

Jacob - Yes, exactly. So, we've been looking for at least a few years now for different ways to be able to get cells to express or make a lot of IFITM3 in the beginning before a virus infection is present.

Chris - Right. So the idea would be, it's almost like putting the cells into defensive mode so they're already capable of warding off virus before it even arrives and then when some virus does come on the scene, it just can't get in.

Jacob - Yes, exactly. So, we've known for a long time that if we can get cells to express or make a lot of IFITM3, they're very resistant to flu infection right from the start.

Chris - How does one go about doing that then? How can you boost the amount of this IFITM3 signal?

Jacob - So, what we found is that one of the reasons that IFITM3 levels are so low is that the cells mark IFITM3 to be degraded. This involves another enzyme called NEDD4. Now, when we deplete cells of NEDD4 then we see that IFITM3 is able to accumulate even in the absence of infection.

Chris - So, it's a bit like the cell adds a 'best before date' like supermarkets do, to the IFITM3 and the cell comes along says, "Right. Your time is up" and hoiks it off. What you're doing is effectively removing the shelf stacker who would normally go around in the supermarket removing the stuff that's over its 'best before date' so the protein stays there on the cell surface, doing its job for longer so you get a more pronounced effect.

Jacob - That's exactly right. We found a way to extend the half-life of IFITM3 by eliminating the protein NEDD4.

Chris - What would be the implication then? If you're successful and you can make a drug that will do this in a human being, what would be the implication? Why is this an important discovery?

Jacob - So, what IFITM3 does is it really inhibits all strains of the flu that we've ever tested. So in that way, it would be protective against even new and emerging strains of flu.

Chris - And that means that the eternal search for the next vaccine which the World Health Organisation spends a fortune doing every year, and occasionally gets wrong like it did last year in some respects, that wouldn't matter anymore because we wouldn't need to keep making new flu vaccines. We could just give people this agent that you're going to invent instead.

Jacob - Right. So, I think that this would definitely be a complimentary strategy to vaccination especially if there was a new virus that emerges that we haven't yet developed a vaccine for.

Chris - So we're probably a little bit early for next flu season so we shouldn't hold our breath there, but there's certainly hope. Will it work against other viruses or is this an anti-flu effect exclusively? I'm thinking of, have you actually got the cure for the common cold here too?

Jacob - That's actually a really good question. IFITM3 does inhibit other viruses. It inhibits viruses that enter cells in a similar way to flu. And some of those viruses are things like dengue virus, west Nile virus, and even Ebola virus.

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