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Opinion: How your body clock helps determine whether you’ll get ill or not

Anonymous — Wed, 17 Aug 2016 10:55:31 +0000

From vitamin C and echinacea to warm clothes and antibacterial soap, there’s no shortage of ideas about how to prevent and manage colds and flu. Unfortunately, many of these are not based on solid scientific evidence. In fact, medical researchers are only starting to unravel the range of factors that affect our susceptibility to getting an infection. Now we have discovered that our body clock plays an important role – making us more prone to get infected at certain times of the day.

It is perhaps easy to forget that we have co-evolved on this planet with micro-organisms, including bacteria, which may be either beneficial or harmful to us. Similarly, viruses cannot copy themselves without help from our cells. Without us, they simply wouldn’t exist.

So what happens when a virus encounters a cell? First, it has to get in through a protective barrier called the cell membrane. Then it has to hijack the interior of the “host” cell to subvert it and divert all resources to copy itself millions of times. Once an army of identical clones is formed, it breaks out of the cell, usually destroying it in the process. Imagine millions of these new viruses then being able to do exactly the same to other cells nearby. ̽��ֱ��cycle goes on, with often rapid amplification of the virus through a tissue, and then through the body.

That’s if the virus had it all its own way … But there is always a battle in play between invading organisms and our bodies. Our immune system counteracts the invading organisms and will invoke mechanisms to stop the virus entering, replicating and spreading. This defence system works at the level of individual cells in the body, but also in specialised tissues of the body that are designed to mount a response to such invasions.

It now turns out that our body clock is also an important gatekeeper of virus infections. ̽��ֱ��body clock is an amazing piece of evolutionary biology. It’s thought that most organisms on our planet have a biological clock that keeps track of the 24-hour day. It can do this by orchestrating chemical reactions and genetic switches that rhythmically control thousands of genes in cells in the cell – turning about 15% of all genes on and off across the day and night.

Timely experiment

So why might viruses care about our body clock? Since our cells are miniature factories, making things that the virus must have to copy itself, the virus is less likely to succeed when the production line is shut down. This is what we tested in the laboratory, by infecting cells and mice at different times of the day. We found that viruses are less able to infect in the late afternoon. In contrast, in the early morning, our cells are hives of biosynthetic activity, at least from the virus’s viewpoint. So, if a virus tries to take over a cell in the early day, it is far more likely to succeed, and spread faster, than if it encounters a rather less favourable climate in the evening.

Perhaps even more interestingly, when the clockwork is disrupted, viruses are more prolific at taking over cells and tissues. Such “clock misalignment” can happen when we do shift work, get jet lagged, or experience the phenomenon of “social jet lag”, which is caused by changes in our sleep schedule on our days off. Therefore, it’s important to know about these interactions because it will undoubtedly help us to find ways to ensure better health for ourselves. For example, since we know shift workers are more likely to get infections, it might be a good idea to give them flu vaccinations.

Perhaps nightclub germs aren’t so threatening after all. *sax/Flickr, CC BY-SA

Knowing about the clock and viruses could also help us to design better public health measures to combat virus spread. You could imagine that during a pandemic limiting exposure during the early daytime could be a small but important intervention to try to prevent viral infection from taking hold. Indeed, a recent study by a team at the ̽��ֱ�� of Birmingham showed that vaccinating people against flu in the morning is more effective than in the evening. This principle could be the same for many unrelated viruses.

̽��ֱ��research could also help us crack a longstanding enigma – why do virus infections like flu happen more commonly in the winter months? It turns out that the very same molecular switch – called Bmal1 – that goes up and down in the day and night also changes according to the seasons, going up in the summer and down in the winter. When we artificially lower Bmal1 levels in mice and cells, the virus is able to infect more. As occurs on a daily basis, the waxing and waning of Bmal1 in our bodies could be a reason why we’re less likely to cope with viruses like flu in the winter.

So, if you’re desperate to avoid catching a flu virus that’s been going around the office, rather than trying to boost your immune system with various vitamins, you may want to try to simply work from home in the mornings.

Akhilesh Reddy, Wellcome Trust Senior Fellow in Clinical Sciences at the Department of Clinical Neurosciences, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Akhilesh Reddy (Department of Clinical Neurosciences) discusses how circadian rhythms can affect whether you get the flu.

Claus Rebler

Sick

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Time of day influences our susceptibility to infection, study finds

cjb250 — Mon, 15 Aug 2016 19:00:21 +0000

When a virus enters our body, it hijacks the machinery and resources in our cells to help it replicate and spread throughout the body. However, the resources on offer fluctuate throughout the day, partly in response to our circadian rhythms – in effect, our body clock. Circadian rhythms control many aspects of our physiology and bodily functions – from our sleep patterns to body temperature, and from our immune systems to the release of hormones. These cycles are controlled by a number of genes, including Bmal1 and Clock.

To test whether our circadian rhythms affect susceptibility to, or progression of, infection, researchers at the Wellcome Trust-Medical Research Council Institute of Metabolic Science, ̽��ֱ�� of Cambridge, compared normal ‘wild type’ mice infected with herpes virus at different times of the day, measuring levels of virus infection and spread. ̽��ֱ��mice lived in a controlled environment where 12 hours were in daylight and 12 hours were dark.

̽��ֱ��researchers found that virus replication in those mice infected at the very start of the day – equivalent to sunrise, when these nocturnal animals start their resting phase – was ten times greater than in mice infected ten hours into the day, when they are transitioning to their active phase. When the researchers repeated the experiment in mice lacking Bmal1, they found high levels of virus replication regardless of the time of infection.

“ ̽��ֱ��time of day of infection can have a major influence on how susceptible we are to the disease, or at least on the viral replication, meaning that infection at the wrong time of day could cause a much more severe acute infection,” explains Professor Akhilesh Reddy, the study’s senior author. “This is consistent with recent studies which have shown that the time of day that the influenza vaccine is administered can influence how effectively it works.”

In addition, the researchers found similar time-of-day variation in virus replication in individual cell cultures, without influence from our immune system. Abolishing cellular circadian rhythms increased both herpes and influenza A virus infection, a dissimilar type of virus – known as an RNA virus – that infects and replicates in a very different way to herpes.

Dr Rachel Edgar, the first author, adds: “Each cell in the body has a biological clock that allows them to keep track of time and anticipate daily changes in our environment. Our results suggest that the clock in every cell determines how successfully a virus replicates. When we disrupted the body clock in either cells or mice, we found that the timing of infection no longer mattered – viral replication was always high. This indicates that shift workers, who work some nights and rest some nights and so have a disrupted body clock, will be more susceptible to viral diseases. If so, then they could be prime candidates for receiving the annual flu vaccines.”

As well as its daily cycle of activity, Bmal1 also undergoes seasonal variation, being less active in the winter months and increasing in summer. ̽��ֱ��researchers speculate that this may help explain why diseases such as influenza are more likely to spread through populations during winter.

Using cell cultures, the researchers also found that herpes viruses manipulate the molecular ‘clockwork’ that controls our circadian rhythms, helping the viruses to progress. This is not the first time that pathogens have been seen to ‘game’ our body clocks: the malaria parasite, for example, is known to synchronise its replication cycle with the host’s circadian rhythm, producing a more successful infection.

“Given that our body clocks appear to play a role in defending us from invading pathogens, their molecular machinery may offer a new, universal drug target to help fight infection,” adds Professor Reddy.

̽��ֱ��research was mostly funded by the Wellcome Trust and the European Research Council.

Reference
Edgar, RS et al. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock. PNAS; e-pub 15 Aug 2016; DOI: 10.1073/pnas.1601895113

We are more susceptible to infection at certain times of the day as our body clock affects the ability of viruses to replicate and spread between cells, suggests new research from the ̽��ֱ�� of Cambridge. ̽��ֱ��findings, published today in the Proceedings of the National Academy of Sciences, may help explain why shift workers, whose body clocks are routinely disrupted, are more prone to health problems, including infections and chronic disease.

̽��ֱ��time of day of infection can have a major influence on how susceptible we are to the disease, or at least on the viral replication, meaning that infection at the wrong time of day could cause a much more severe acute infection

Akhilesh Reddy

Alexandra Bilham

Clock

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