̽��ֱ�� of Cambridge - Colin Russell

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

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Scientists ‘must not become complacent’ when assessing pandemic threat from flu viruses

cjb250 — Wed, 15 Oct 2014 12:30:00 +0000

Influenza pandemics arise when a new virus strain – against which humans have yet to develop widespread immunity – spreads in the human population. There have been five such pandemics in the past 100 years, the worst of which – the 1918 Spanish Flu – cost 50 million lives worldwide. Of these pandemics, three are thought to have spread from birds and one from pigs. However, pandemic influenza strains represent only a tiny fraction of the total diversity of influenza viruses that exist in nature; the threats posed by the majority of these viruses are poorly understood. Assessing which viruses pose the greatest risk of causing the next human pandemic is an enormous challenge.

Steven Riley from Imperial College London, an author of the study, says: “There are too many strains of influenza viruses out there in non-human hosts to make it feasible to make preparations against each one. Instead, we need to get better at assessing the pandemic risks so that we know where best to focus our efforts. At the moment, this assessment is largely driven by a simple idea: animal viruses that cause sporadic human infections pose a greater risk than viruses that have not been documented to infect humans. But in fact, none of the viruses that caused the major pandemics of the last century were detected in humans before they emerged in their pandemic form.”

Writing in the journal eLife, the scientists set out the steps that they consider necessary to increase our ability to assess pandemic risk. As influenza virus genome sequencing becomes cheaper, faster and more readily available, the data it generates has the potential to transform the research community’s ability to predict the pandemic risk. However, it remains extremely difficult to predict just from a virus’s genome what symptoms it will elicit in its host – and hence how deadly the virus is. ̽��ֱ��researchers call for better integration of experimental data, computational methods and mathematical models, in conjunction with refinements to surveillance methodology.

However, they say that scientific insights into non‐human influenza viruses must not give way to complacency that the most substantial threats have been identified and characterized. They point out that several recent strains including the 2009 H1N1 “swine flu” pandemic virus and the recently emerged H7N9 viruses in China highlight the importance of remaining vigilant against as-yet unrecognized high risk viruses and the value of surveillance for influenza viruses in humans.

“No one can say with anything close to a hundred percent certainty when or where the next pandemic will start or which virus will cause it,” says Dr Colin Russell from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner.

“We need to be prepared for a swift response, with coordinated action, to help mitigate the spread of the next pandemic virus. Without developing this ability to respond, we will have spent billions building systems just for watching the next pandemic unfold.”

̽��ֱ��research was supported in part by the Research and Policy for Infectious Disease Dynamics program of the US Department of Homeland Security and the National Institutes of Health.

Reference
Russell, CA et al. Improving pandemic influenza risk assessment. eLife; 15 Oct 2015

As our ability to assess the pandemic risk from strains of influenza virus increases with the latest scientific developments, we must not allow ourselves to become complacent that the most substantial threats have been identified, argue an international consortium of scientists.

We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner

Colin Russell

MIKI Yoshihito

New influenza viruses (cropped)

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Cambridge researchers support the WHO

lw355 — Thu, 20 Dec 2012 14:27:31 +0000

̽��ֱ��WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases recognises the work of Cambridge researchers who work in this area.

̽��ֱ��Centre, directed by Professor Derek Smith in the Department of Zoology, has pan-university and highly interdisciplinary activities with members of the Department of Zoology, Department of Pathology and Department of Veterinary Medicine in the School of Biological Sciences, members of the School of Clinical Medicine, and also from the Department of Architecture and Computer Laboratory.

̽��ֱ��Centre is linked with researchers throughout the world and is concerned with global infectious disease issues that affect not only the developed world, but also the developing world. For example the Centre has close cooperation with the Cambridge in Africa program, in particular on researching the dengue virus.

One of the long-standing activities of the Collaborating Centre is to provide support for WHO activities in the global surveillance of influenza and other pathogens – including dengue and enterovirus 71 – as well as recommendations on suitable vaccine strains for use in these and other emerging and re-emerging diseases.

Each year, influenza infects 5–15% of the world’s population and kills up to half a million people – a figure that can rise to many millions in the event of a pandemic. Spearheading the annual race to identify the best vaccine to combat seasonal flu, the WHO collates information about the flu viruses in circulation worldwide in the preceding months.

As part of this process, Dr Colin Russell in the Department of Zoology curates a global database of information on the rapidly changing variations (called antigenic differences) in the influenza coat protein – the part that makes it difficult for our immune system to recognise flu from one year to the next.

“Our WHO Collaborating Centre is in the privileged position of informing public health initiatives through highly translational scientific research, using technology that allows real-time detection of circulating viruses that escape protection conferred by current vaccines,” said Smith.

̽��ֱ��Centre uses a technique called antigenic cartography developed by Smith with Dr Alan Lapedes (Los Alamos National Laboratory, New Mexico) and Professor Ron Fouchier (Erasmus Medical Center, Rotterdam). ̽��ֱ��technique analyses antigenic differences between pathogens, allowing real-time detection of circulating viruses that escape protection conferred by current vaccine strains. “Antigenic maps allow us to make sense of vast amounts of difficult binding assay data. One can see at a glance the global picture of decades of viral evolution,” added Smith.

In addition, the Centre carries out research on the evolution of pandemic influenza. “We can start asking questions such as how close is nature to evolving an aerosol-transmissible form of bird flu that can be transmitted from human to human, as opposed to the varieties we have seen so far that have been passed to individuals in close contact with infected birds,” said Smith.

̽��ֱ��work of the Centre is underpinned by the activities of Cambridge Infectious Diseases, a multidisciplinary community of researchers that promotes, develops and supports initiatives which focus on infectious diseases.

WHO Collaborating Centres are designated by the WHO Director-General to carry out activities in support of the Organization’s programmes on areas such as nursing, occupational health, communicable diseases, nutrition, mental health, chronic diseases and health technologies.

For more information, please visit www.whocc.infectiousdisease.cam.ac.uk/ or download the WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases brochure.

A newly designated Collaborating Centre at the ̽��ֱ�� of Cambridge will support the World Health Organization (WHO) in detecting and responding to major epidemic- and pandemic-prone diseases.

Our WHO Collaborating Centre is in the privileged position of informing public health initiatives through highly translational scientific research.

Professor Derek Smith

Stillvision

Researchers at the WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases

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