Body clock impacts infection rates

22 August 2016

Interview with

Dr Akhilesh Reddy, University of Cambridge

Sleeping on the airportMany people complain that going on holiday causes them to catch a cold, and now we may know why!  The reason, scientists at Cambridge University are suggesting, could be down to the jet lag! They've found that disruption to your body clock makes infecting viruses grow up to ten times more efficiently in your cells. Akhilesh Reddy spoke to Chris Smith about their discovery...

Akh - Well we kind of figured that viruses are unusual in terms of microorganisms that infect the body because they actually need our cells in order to replicate. And, therefore, because every single cell in the body has this biological, or circadian 24 hour clock within it, we thought that there might be a particular time of the day when all of the things that the virus required would be increased, and at other times when they would be decreased. So, if the virus comes along at one time of day it could capitalise on the cell that is making all the stuff that it wants and another time of day it wouldn't be able to replicate as well because all of the stuff that it needs isn't there simply.

Chris - Because the role of that clock is, basically, to prepare or optimise the metabolic activity in your cells to meet the demands of the day ahead. So that the cells are turning on their energy supply in the morning when you need to get up and face the challenges of the day, and they're turning down the thermostat at night when you need to go to sleep because you don't want to have the coal-fired power station running away at a furious pace when you don't need that energy?

Akh - Absolutely. It's a mechanism to essentially ensure your cells run efficiently so you're not wasting energy when you don't require it to be used.

Chris - But, obviously, if the cells are not very active they're not as good a home for a virus as when they're running full pelt. Is that the case then when you put viruses into cells do you see that's what's happening?

Ak - Exactly.  That's exactly what we saw in cells and in live animals as well. And this was done in mouse models but also in free cells which are very similar between mouse and human.

Chris - Do cells in a dish have a clock?

Ak - Yes, exactly, yes. Cells in a dish have a clock and we can synchronise those clocks by doing various things in the lab. And what we did was to synchronise these cells, or infect mice at different time of day and have a look at how quickly that virus then  spreads over a few days. And we found that if you infect in the morning, then you're much more likely to see a higher rate of infection than if you didn't do it before dusk.

Chris - This is mouse morning because mice are nocturnal aren't they? So they're actually going to bed when we're getting up so for them it's nighttime but it's really morning, if you see what I mean.

Akh - Yes, exactly. But the complicated thing in terms of how you look at clocks is that actually, the genes that go up and down in us and mice are, actually, identical in terms of their structure and also, the phasing is the same, so we interpret those clock/gene signals in the opposite way. So we live in the daytime, they live at nighttime. And in the brain in fact, bizarrely, the genes are going up and down exactly the same in both species, but the way that's interpreted by the body is actually opposite. So we don't exactly know what happens in humans.

Chris - So we have this body clock - it's a genetic clock where you've got a gene that ticks on and it turns on another gene, which turns on another gene, and that feeds back and turns of the first gene, and this ticks round - it takes about 24 hours. It changes the activity of cells as it does so. Now I started this interview by saying that this does help us to explain the holiday lurgy syndrome when you catch stuff when you go away. Now a part of that must be when you're sitting on an aircraft for hours doesn't help but, if you get jet lagged, that is going to screw around with your body clock so that, presumably, will make your cells more susceptible to growing viruses more?

Akh - Absolutely, yes. So we did an experiment where we messed up the clock using a genetic trick, and we looked at both cells and animals, and when we infected them they were something like three or four times more affected by the virus than the normal cells, essentially. So that's very similar to what happens in people who have jet lag or people who fly across the world, as you say.

Chris - Does this mean we could use this therapeutically if we understand the importance of the body clock to a range of diseases including virus infections? Could this change the way in which we treat these diseases?

Akh - We believe so. So when we did this experiment we used two different types of viruses, so the clock seems to be important for both of these viruses that replicate by completely different means. So the idea is that instead of having an antiviral that will actively boost your natural immune system at one time of day or another, instead of having one for each individual virus, you might just be able to boost your own immunity to multiple different viruses if you could switch that on or off, and that's exactly what we're trying to target at the moment.

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