̽��ֱ�� of Cambridge - influenza

System to auto-detect new variants will inform better response to future infectious disease outbreaks

jg533 — Wed, 01 Jan 2025 16:00:35 +0000

̽��ֱ��new approach uses samples from infected humans to allow real-time monitoring of pathogens circulating in human populations, and enable vaccine-evading bugs to be quickly and automatically identified. This could inform the development of vaccines that are more effective in preventing disease.

̽��ֱ��approach can also quickly detect emerging variants with resistance to antibiotics. This could inform the choice of treatment for people who become infected – and try to limit the spread of the disease.

It uses genetic sequencing data to provide information on the genetic changes underlying the emergence of new variants. This is important to help understand why different variants spread differently in human populations.

There are very few systems in place to keep watch for emerging variants of infectious diseases, apart from the established COVID and influenza surveillance programmes. ̽��ֱ��technique is a major advance on the existing approach to these diseases, which has relied on groups of experts to decide when a circulating bacteria or virus has changed enough to be designated a new variant.

By creating ‘family trees’, the new approach identifies new variants automatically based on how much a pathogen has changed genetically, and how easily it spreads in the human population – removing the need to convene experts to do this.

It can be used for a broad range of viruses and bacteria and only a small number of samples, taken from infected people, are needed to reveal the variants circulating in a population. This makes it particularly valuable for resource-poor settings.

̽��ֱ��report was published in the journal Nature.

“Our new method provides a way to show, surprisingly quickly, whether there are new transmissible variants of pathogens circulating in populations – and it can be used for a huge range of bacteria and viruses,” said Dr Noémie Lefrancq, first author of the report, who carried out the work at the ̽��ֱ�� of Cambridge’s Department of Genetics.

Lefrancq, who is now based at ETH Zurich, added: “We can even use it to start predicting how new variants are going to take over, which means decisions can quickly be made about how to respond.”

“Our method provides a completely objective way of spotting new strains of disease-causing bugs, by analysing their genetics and how they’re spreading in the population. This means we can rapidly and effectively spot the emergence of new highly transmissible strains,” said Professor Julian Parkhill, a researcher in the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine who was involved in the study.

Testing the technique

̽��ֱ��researchers used their new technique to analyse samples of Bordetella pertussis, the bacteria that causes whooping cough. Many countries are currently experiencing their worst whooping cough outbreaks of the last 25 years. It immediately identified 3 new variants circulating in the population that had been previously undetected.

“ ̽��ֱ��novel method proves very timely for the agent of whooping cough, which warrants reinforced surveillance given its current comeback in many countries and the worrying emergence of antimicrobial resistant lineages,” said Professor Sylvain Brisse, Head of the National Reference Center for whooping cough at Institut Pasteur, who provided bioresources and expertise on Bordetella pertussis genomic analyses and epidemiology.

In a second test, they analysed samples of Mycobacterium tuberculosis, the bacteria that causes Tuberculosis. It showed that 2 variants with resistance to antibiotics are spreading.

“ ̽��ֱ��approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible,” said Professor Henrik Salje in the ̽��ֱ�� of Cambridge’s Department of Genetics, senior author of the report.

He added: “If we see a rapid expansion of an antibiotic-resistant variant, then we could change the antibiotic that’s being prescribed to people infected by it, to try and limit the spread of that variant.”

̽��ֱ��researchers say this work is an important piece in the larger jigsaw of any public health response to infectious disease.

A constant threat

Bacteria and viruses that cause disease are constantly evolving to be better and faster at spreading between us. During the COVID pandemic, this led to the emergence of new strains: the original Wuhan strain spread rapidly but was later overtaken by other variants, including Omicron, which evolved from the original and were better at spreading. Underlying this evolution are changes in the genetic make-up of the pathogens.

Pathogens evolve through genetic changes that make them better at spreading. Scientists are particularly worried about genetic changes that allow pathogens to evade our immune system and cause disease despite us being vaccinated against them.

“This work has the potential to become an integral part of infectious disease surveillance systems around the world, and the insights it provides could completely change the way governments respond,” said Salje.

̽��ֱ��research was primarily funded by the European Research Council.

Reference: Lefrancq, N et al: ‘Learning the fitness dynamics of pathogens from phylogenies.’ January 2025, DOI: 10.1038/s41586-024-08309-9

Researchers have come up with a new way to identify more infectious variants of viruses or bacteria that start spreading in humans – including those causing flu, COVID, whooping cough and tuberculosis.

̽��ֱ��approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible.

Henrik Salje

Milan Krasula on Getty

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Gone fishing: highly accurate test for common respiratory viruses uses DNA as ‘bait’

sc604 — Mon, 16 Jan 2023 16:00:00 +0000

̽��ֱ��test uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. ̽��ֱ��results are reported in the journal Nature Nanotechnology.

̽��ֱ��winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

“Many respiratory viruses have similar symptoms but require different treatments: we wanted to see if we could search for multiple viruses in parallel,” said Filip Bošković from Cambridge’s Cavendish Laboratory, the paper’s first author. “According to the World Health Organization, respiratory viruses are the cause of death for 20% of children who die under the age of five. If you could come up with a test that could detect multiple viruses quickly and accurately, it could make a huge difference.”

For Bošković, the research is also personal: as a young child, he was in hospital for almost a month with a high fever. Doctors could not figure out the cause of his illness until a PCR machine became available.

“Good diagnostics are the key to good treatments,” said Bošković, who is a PhD student at St John’s College, Cambridge. “People show up at hospital in need of treatment and they might be carrying multiple different viruses, but unless you can discriminate between different viruses, there is a risk patients could receive incorrect treatment.”

PCR tests are powerful, sensitive and accurate, but they require a piece of genome to be copied millions of times, which takes several hours.

̽��ֱ��Cambridge researchers wanted to develop a test that uses RNA to detect viruses directly, without the need to copy the genome, but with high enough sensitivity to be useful in a healthcare setting.

“For patients, we know that rapid diagnosis improves their outcome, so being able to detect the infectious agent quickly could save their life,” said co-author Professor Stephen Baker, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease. “For healthcare workers, such a test could be used anywhere, in the UK or in any low- or middle-income setting, which helps ensure patients get the correct treatment quickly and reduce the use of unwarranted antibiotics.”

̽��ֱ��researchers based their test on structures built from double strands of DNA with overhanging single strands. These single strands are the ‘bait’: they are programmed to ‘fish’ for specific regions in the RNA of target viruses. ̽��ֱ��nanobaits are then passed through very tiny holes called nanopores. Nanopore sensing is like a ticker tape reader that transforms molecular structures into digital information in milliseconds. ̽��ֱ��structure of each nanobait reveals the target virus or its variant.

̽��ֱ��researchers showed that the test can easily be reprogrammed to discriminate between viral variants, including variants of the virus that causes COVID-19. ̽��ֱ��approach enables near 100% specificity due to the precision of the programmable nanobait structures.

“This work elegantly uses new technology to solve multiple current limitations in one go,” said Baker. “One of the things we struggle with most is the rapid and accurate identification of the organisms causing the infection. This technology is a potential game-changer; a rapid, low-cost diagnostic platform that is simple and can be used anywhere on any sample.”

A patent on the technology has been filed by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm, and co-author Professor Ulrich Keyser has co-founded a company, Cambridge Nucleomics, focused on RNA detection with single-molecule precision.

“Nanobait is based on DNA nanotechnology and will allow for many more exciting applications in the future,” said Keyser, who is based at the Cavendish Laboratory. “For commercial applications and roll-out to the public we will have to convert our nanopore platform into a hand-held device.”

“Bringing together researchers from medicine, physics, engineering and chemistry helped us come up with a truly meaningful solution to a difficult problem,” said Bošković, who received a 2022 PhD award from Cambridge Society for Applied Research for this work.

̽��ֱ��research was supported in part by the European Research Council, the Winton Programme for the Physics of Sustainability, St John’s College, UK Research and Innovation (UKRI), Wellcome, and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Reference:
Filip Bošković et al. ‘Simultaneous identification of viruses and viral variants with programmable DNA nanobait.’ Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01287-x

A new test that ‘fishes’ for multiple respiratory viruses at once using single strands of DNA as ‘bait’, and gives highly accurate results in under an hour, has been developed by Cambridge researchers.

Good diagnostics are the key to good treatments

Filip Bošković

Natalia Gdovskaia via Getty Images

Doctor examining a patient

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Spanish Flu: a warning from history

Anonymous — Fri, 30 Nov 2018 09:22:27 +0000

̽��ֱ��early origins and initial geographical starting point of the pandemic still remain a mystery but in the summer of 1918, there was a second wave of a far more virulent form of the influenza virus than anyone could have anticipated.

Soon dubbed ‘Spanish Flu’ after its effects were reported in the country’s newspapers, the virus rapidly spread across much of the globe to become one of the worst natural disasters in human history.

Doctors, nurses and volunteers were left helpless as their patients, the majority previously healthy young adults, languished and died from respiratory failure. There is now a broad consensus among experts that in just three years, Spanish Flu killed between fifty and one hundred million people. Despite this, public awareness of the disaster and the ongoing threat posed by influenza remains limited.

To mark the centenary and to highlight vital scientific research, the ̽��ֱ�� of Cambridge has made a new film exploring what we have learnt about Spanish Flu, the urgent threat posed by influenza today, and how scientists are preparing for future pandemics. ̽��ֱ��film presents original photographs from the 1918 outbreak and exclusive interviews with four leading experts:

Dr Mary Dobson, a historian of infectious diseases
Professor Derek Smith, Director of Cambridge’s Centre for Pathogen Evolution
Dr AJ te Velthuis, a virologist studying how RNA viruses amplify, mutate and cause disease
Professor Julia Gog, a mathematician of infectious diseases including influenza

One hundred years ago, celebrations marking the end of the First World War were cut short by the onslaught of a devastating disease: the 1918-19 influenza pandemic.

Spanish Flu: A Warning from History

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'Significant breakthrough' in understanding the deadly nature of pandemic influenza

sjr81 — Tue, 18 Sep 2018 14:59:28 +0000

Influenza is one of the main infectious diseases in humans. Seasonal influenza viruses account for about 650,000 deaths per year, whereas pandemic strains such as the 1918 H1N1 pandemic virus have been linked to 50-100 million deaths worldwide. Highly pathogenic avian influenza viruses such as the H5N1 and H7N9 strains have a mortality rate of about 50% in humans.

̽��ֱ��reasons for difference in disease severity and lethality caused by seasonal influenza viruses on the one hand, and pandemic and highly pathogenic avian influenza viruses on the other hand is still poorly understood. Previous research has indicated that in infections with the 1918 pandemic virus or infections with an H5N1 avian virus, a powerful immune response is established that leads to death.

This led Dr Aartjan te Velthuis of the ̽��ֱ�� of Cambridge and his colleagues Prof Ervin Fodor, Dr Josh Long and Dr David Bauer of the ̽��ֱ�� of Oxford, to ask what viral molecule can trigger this powerful immune response.

̽��ֱ��British groups first looked to how viruses are detected by the cell. Normally, an infected cell spots the presence of a virus by sensing the genetic material of the virus, RNA in the case of flu.

Work by Dr Richard Randall, a co-author on the manuscript from the ̽��ֱ�� of St Andrews, has shown that influenza viruses are good at hiding their RNA. This observation prompted te Velthuis and his colleagues to look for flu RNA that the virus was not able to hide from the cellular pathogen sensing system. What they found was truncated pieces of the viral genome that the virus had produced in error. ̽��ֱ��researchers called these pieces mini viral RNAs.

Fodor and his colleagues next investigated whether different influenza viruses produce mini viral RNAs at different frequencies and whether there was a link with the strong innate immune response that, for instance, the 1918 pandemic virus induces.

A combination of in vitro and in vivo experiments performed at Oxford and Cambridge, as well as by collaborators Leo Poon of the ̽��ֱ�� of Hong Kong, Debby van Riel of the Erasmus Medical Centre, and Emmie de Wit of the Rocky Mountain Laboratories, revealed indeed a strong correlation between the ability of an influenza virus to generate mini viral RNAs and the amount of inflammation and cell death the virus infection caused.

“We think it is a significant breakthrough and that it is particularly exciting that we are finding this factor a hundred years after the 1918 pandemic,” said Dr te Velthuis.

̽��ֱ��research groups are now continuing their efforts to investigate whether there is a causal link between influenza virus mortality and the production of mini viral RNAs. Together with their latest work, these efforts may help us understand better how influenza viruses cause disease, how we can identify dangerous influenza viruses, and how to develop new antivirals against influenza virus infections.

̽��ֱ��work was funded by the Wellcome Trust, Royal Society, Medical Research Council, NIH, and the Netherlands Organization for Scientific Research.

Researchers at the ̽��ֱ�� of Cambridge and the ̽��ֱ�� of Oxford have discovered a new molecule that plays a key role in the immune response that is triggered by influenza infections. ̽��ֱ��molecule, a so-called mini viral RNA, is capable of inducing inflammation and cell death, and was produced at high levels by the 1918 pandemic influenza virus. ̽��ֱ��findings appeared in Nature Microbiology yesterday (September 17).

We think it is a significant breakthrough and that it is particularly exciting that we are finding this factor a hundred years after the 1918 pandemic.

Aartjan te Velthuis

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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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Threat of novel swine flu viruses in pigs and humans

Anonymous — Wed, 27 Apr 2016 11:21:37 +0000

While swine flu viruses have long been considered a risk for human pandemics, and were the source of the 2009 pandemic H1N1 virus, attention has recently turned to the transmission of flu viruses from humans to pigs.

"Once in pigs, flu viruses from humans continue to evolve their surface proteins, generically referred to as antigens, resulting in a tremendous diversity of novel flu viruses that can be transmitted to other pigs and also to humans," explains first author Nicola Lewis from the ̽��ֱ�� of Cambridge.

"These flu viruses pose a serious threat to public health because they are no longer similar enough to the current human flu strains for our immune systems to recognise them and mount an effective defence. Understanding the dynamics and consequences of this two-way transmission is important for designing effective strategies to detect and respond to new strains of flu."

Humans and pigs both experience regular outbreaks of influenza A viruses, most commonly from H1 and H3 subtypes. Their genetic diversity is well characterised. However, the diversity of their antigens, which shapes their pandemic potential, is poorly understood, mainly due to lack of data.

To help improve this understanding, Lewis and her team created the largest and most geographically comprehensive dataset of antigenic variation. They amassed and characterised antigens from nearly 600 flu viruses dating back from 1930 through to 2013 and collected from multiple continents, including Europe, the US, and Asia. They included nearly 200 viruses that had never been studied before.

Analysis of their data reveals that the amount of antigenic diversity in swine flu viruses resembles the diversity of H1 and H3 viruses seen in humans over the last 40 years, driven by the frequent introduction of human viruses to pigs. In contrast, flu from birds has rarely contributed substantially to the diversity in pigs. However, little is currently known about the antigenic relationship between flu in birds and pigs.

"Since most of the current swine flu viruses are the result of human seasonal flu virus introductions into pigs, we anticipate at least some cross-protective immunity in the human population, which could potentially interfere with a re-introduction of these viruses. For example, the H1N1pdm09 viruses circulating in both humans and pigs are antigenically similar and therefore likely induce some immunity in both hosts," says Lewis.

"However, for the H1 1C, H3 3A, and H3 3B human seasonal lineages in pigs, the risk of re-introduction into the human population increases with the number of people born after the circulation of the human precursor virus, and is increased by the antigenic evolution of these viruses in pigs. Earlier introduced lineages of human H1 and H3 viruses therefore pose the greatest current risk to humans, due to the low or negligible predicted levels of cross-immunity in individuals born since the 1970s."

Swine flu causes symptoms such as coughing, fever, body aches, chills, and fatigue in humans. Pigs can also experience fever and coughing (barking), along with discharge from the nose or eyes, breathing difficulties, eye redness or inflammation, and going off feed - although some display no clinical signs at all.

Vaccination to control flu in pigs is used extensively in the US and occasionally in other regions. Control strategies vary by region, with some countries not using any vaccinations, while others produce herd-specific vaccines for individual producers. There is no formal system for matching vaccine strains with circulating strains, however, and no validated protocols for standardisation and effective vaccine use.

" ̽��ֱ��significant antigenic diversity that we see in our data means it is highly unlikely that one vaccine strain per subtype would be effective on a global scale, or even in a given region," says co-author Colin Russell, also from the ̽��ֱ�� of Cambridge.

"Our findings therefore have important implications for developing flu vaccines for pigs. They also emphasise the need for more focused surveillance in areas with a high pig population density, such as China, and situations where humans and pigs have close contact, in order to better assess the incidence of transmission between the animals and risk of spreading to humans."

Reference:

̽��ֱ��paper ' ̽��ֱ��global antigenic diversity of swine influenza A viruses' can be freely accessed online at http://dx.doi.org/10.7554/eLife.12217.

Originally published as a press release by eLife.

̽��ֱ��wide diversity of flu in pigs across multiple continents, mostly introduced from humans, highlights the significant potential of new swine flu strains emerging, according to a new study.

These flu viruses pose a serious threat to public health because they are no longer similar enough to the current human flu strains for our immune systems to recognise them

Nicola Lewis

Robert Shell

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Virus evolution and human behaviour shape global patterns of flu movement

cjb250 — Mon, 08 Jun 2015 15:00:18 +0000

In the study, an international team of researchers led by the ̽��ֱ�� of Cambridge and the Fred Hutchinson Cancer Research Center, and including all five World Health Organization (WHO) Influenza Collaborating Centres, reports surprising differences between the various types of seasonal flu virus, which they show to be due to the rate at which the different viruses evolve.

There are four types of influenza viruses that cause seasonal flu in humans: two influenza A viruses (H3N2 and H1N1) and two influenza B viruses (Yamagata and Victoria). While H3N2 viruses are the most common of the seasonal influenza viruses, H1N1 and B viruses also cause epidemics worldwide each year, hence the WHO selects representative strains of all four A and B viruses for inclusion in the seasonal influenza vaccine each year.

Importantly, all four of the viruses cause indistinguishable symptoms and evolve by similar mechanisms to escape immunity induced by prior infections and vaccinations. This ‘antigenic’ evolution is part of why people get influenza multiple times over the course of their lives.

In 2008, an international team led by scientists from the ̽��ֱ�� of Cambridge, writing in the journal Science, showed that H3N2 viruses circulate continuously in east and southeast Asia throughout the year, spreading to the rest of the world each year to cause seasonal flu epidemics. Given the fundamental similarities between H3N2, H1N1, and B infection it was thought that they would also emerge from east and southeast Asia to cause yearly epidemics worldwide. However, the work published today in Nature shows that in fact, H1N1 and B viruses behave very differently from H3N2 viruses.

Senior author Dr Colin Russell, from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, UK, says: “While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide. This continuous circulation gives rise to a huge diversity in H1N1 and B viruses circulating globally.”

Interestingly, the researchers found that sometimes new H1N1 and B variants emerge from outside east and southeast Asia and are subsequently seeded into Asia, while in other cases H1N1 and B variants circulate in Asia for years without spreading globally.

“It’s really surprising to find that the H3N2 viruses are unique among the seasonal influenza viruses,” adds first author Dr Trevor Bedford from the Fred Hutchinson Cancer Research Center in Seattle, USA. “It’s almost as surprising to find that the differences among viruses are associated with a simple phenomenon: how quickly the viruses evolve antigenically.”

̽��ֱ��Nature study finds that the rate of global movement of each virus, and its ability to circulate continuously between epidemics, is shaped by how quickly that virus changes its coat to escape immunity in the human population. Viruses that evolve quickly, in particular H3N2, spread around the world rapidly, but die out quickly between epidemics. Viruses that evolve more slowly, like H1N1 and B viruses, spread around the world more slowly but are also better at circulating continuously between epidemics.

̽��ֱ��key element about global movement is who is getting infected: faster evolving viruses, like H3N2, can infect adults, who tend to travel more frequently than children, providing more opportunities for the virus to spread. Conversely, more slowly evolving viruses, such as H1N1 and B viruses, primarily infect children. Children get sick with all four seasonal flu viruses, but H3N2 evolves faster so it infects adults more often. This leads to a greater proportion of adult infections with H3N2 relative to H1N1 and B viruses, and faster spread of H3N2 viruses.

“Ultimately, this means that we can look at the viruses circulating in Asia to get a good idea of which H3N2 virus might spread worldwide, but for H1N1 and B it’s tremendously variable and the dominant variant can vary from one region of the world to another,” says Dr Russell.

̽��ֱ��Nature study also sheds important light on the role of India in the global spread of seasonal influenza viruses. Scientists and public health officials had long known that China and Southeast Asia were important for the evolution and spread of seasonal influenza viruses. However, based on the analysis of an extensive collection of viruses from India, it is now clear that India may be as central as China to the ongoing evolution of seasonal influenza viruses.

“ ̽��ֱ��focus of influenza research in the past has been on China and southeast Asia, but it seems obvious now that surveillance and public health in India, home to over one sixth of the world’s population, should be a high priority for further development to help safeguard India and the world against seasonal flu,” says Dr Mandeep Chadha of the National Institute of Virology, Pune, India.

̽��ֱ��research was primarily funded by the Royal Society and US National Institutes of Health with extensive involvement of the World Health Organization’s Global Influenza Surveillance and Response System.

Reference
Bedford, T et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature; 8 June 2015.

̽��ֱ��global movement patterns of all four seasonal influenza viruses are illustrated in research published today in the journal Nature, providing a detailed account of country-to-country virus spread over the last decade and revealing unexpected differences in circulation patterns between viruses.

While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide

Colin Russell

Matteo Bagnoli

influenza

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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