Morens & Taubenberger - Influenza Viruses: Breaking All the Rules

BSL-4 Lab Worker - Photo Credit –USAMRIID

 

 

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Perhaps the most memorable line from the movie Contagion came when Laurence Fishburne, as the director of the CDC said, “Someone doesn't have to weaponize the bird flu. The birds are doing that.”

 

Nevertheless, there has been much debate in recent years over the wisdom of creating new, potentially dangerous, life forms in the laboratory.  Projects that, at least in view of some biosecurity experts, could pose a significant danger to the public.

 

Last year, the United States' Office of Science Policy at the NIH released a 4 page set of guidelines for DURC (Duel Use Research of Concern) projects, and ordered a review of all current life sciences projects.

 

For those unfamiliar with the lexicon of biomedical research, DURC in this new policy is defined as:

 

. . . life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment,

 

While this new policy does not automatically halt or defund research found to meet the DURC definition, it does require greater agency oversight and an assessment of the risks and benefits of any research, along with the development of appropriate risk and safety measures.

 

The debate continues, however over the safety, and advisability, of some of these lab experiments.

 

Today in mBio we’ve a perspective from noted virologist Jeffery K. Taubenberger & epidemiologist and medical historian David M. Morens on how nature continually conducts these types of experiments 24/7, without regard for the rules of mankind.

 

Regardless of how you feel about this type of research, you’ll want to read:

 

 

Influenza Viruses: Breaking All the Rules

Jeffery K. Taubenberger^a, David M. Morens^b

Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases^a

Office of the Director,^b National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

ABSTRACT

Influenza A viruses (IAV) are significant pathogens able to repeatedly switch hosts to infect multiple avian and mammalian species, including humans. The unpredictability of IAV evolution and interspecies movement creates continual public health challenges, such as the emergence of the 2009 pandemic H1N1 virus from swine, as well as pandemic threats from the ongoing H5N1 and the recent H7N9 epizootics. In the last decade there has been increased concern about the “dual use” nature of microbiology, and a set of guidelines covering “dual use research of concern” includes seven categories of potentially problematic scientific experiments. In this Perspective, we consider how in nature IAV continually undergo “dual use experiments” as a matter of evolution and selection, and we conclude that studying these properties of IAV is critical for mitigating and preventing future epidemics and pandemics.

 

The views expressed in this article do not necessarily reflect the views of the journal or of ASM.

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mBio: An H7N9 Perspective by Morens, Fauci & Taubenberger

Credit CDC

 

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In an article that appears later today  in the open access journal mBio, well known NIH scientists and researchers David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci describe the history of H7 influenza viruses both in animals and in humans, and discuss why China’s emerging H7N9 virus is viewed with concern.

 

I’ll update this blog with a link to the article when it goes live, but for now we have a press release from the American Society for Microbiology, which provides us with some details.

 

UPDATED:

 

H7N9 Avian Influenza A Virus and the Perpetual Challenge of Potential Human Pandemicity

David M. Morens, Jeffery K. Taubenberger and Anthony S. Fauci doi:10.1128/mBio.00445-13

 

 

 

 

H7N9 influenza: History of similar viruses gives cause for concern

The H7N9 avian flu strain that emerged in China earlier this year has subsided for now, but it would be a mistake to be reassured by this apparent lull in infections. The virus has several highly unusual traits that paint a disquieting picture of a pathogen that may yet lead to a pandemic, according to lead scientists from the National Institute of Allergy and Infectious Diseases. David Morens, Jeffery Taubenberger, and Anthony Fauci, in a paper published in mBio®, the online open-access journal of the American Society for Microbiology, describe the history of H7 viruses in animal and human disease and point out that H7 influenza has a tendency to become established in bird, horse, and swine populations and may spillover repeatedly into humans.

 

“The evidence as a whole is complex and the implications of past outbreaks for predicting the future course of the current H7N9 epizootic [an epidemic among animals] are uncertain," write the authors.

 

The outbreak of H7N9 earlier this year led China to temporarily close scores of live poultry markets in an effort to limit the spread of the virus. Although this previously unrecognized strain of avian influenza A has now been associated with 132 confirmed human infections and 39 related deaths (as of June 14), the rate at which new cases are recognized has dwindled in recent weeks.

 

In their minireview, Morens, Taubenberger and Fauci point out that despite this apparent hiatus, viruses like H7N9, which have subtype 7 hemagglutinin, are a cause for heightened concern because of several highly unusual characteristics. First, H7 viruses have repeatedly been involved in numerous explosive poultry outbreaks including incidents in New York, Canada, Mexico, the Netherlands, and Italy, and in almost all of these cases the virus eventually spilled over into humans. Also, H7 viruses have the ability to mutate from a low pathogenicity form to a high pathogenicity form in birds, a scenario that can lead to large-scale culling and ultimately to human exposure to the virus among poultry workers.

 

H7N9 also shares many characteristics with another influenza strain that continues to spillover into humans: highly pathogenic avian influenza H5N1. Among other commonalities, both viruses have a clinical picture that includes bilateral pneumonia, acute respiratory distress syndrome, and multi-organ failure, and it appears they are both currently unable to easily infect most humans but cause severe disease in individuals with uncharacterized genetic susceptibilities.

 

The fact that many H7 viruses tend to infect conjunctival cells is also cause for concern. Some, but not all, cases of human H7 infection feature prominent signs and symptoms in the eyes, including itching, swelling, and tearing, that could enhance person-to-person spread in an H7N9 outbreak.

 

The authors point out that many H7 viruses have adapted to infect mammals, including horses and pigs, which raises the possibility that H7N9 could adapt in a similar fashion. The possibility that H7N9 might infect pigs is particularly troubling, as swine are considered a "mixing vessel" for viruses - a breeding ground for novel viral reassortants like the 2009 H1N1 pandemic influenza strain commonly known as "swine flu".

 

The sum of these observations is this: we do not know what H7N9 will do next. Although avian influenza viruses have not caused widespread human transmission in 94 years of surveillance, there have been numerous instances of avian influenza spillover and H7N9 "might arguably be more likely than other avian viruses to become human-adapted," write the authors.

 

Regardless of its future, H7N9 certainly holds lessons for preventing human and animal pandemics. All the unknowns surrounding the virus make a strong case for enhancing basic and applied research into the evolution of influenza viruses and for better integration of influenza virology within human and veterinary public health efforts.

 

"We have a unique opportunity to learn more of influenza's many secrets, and thereby enhance our ability to prevent and control an important disease that seems destined to appear again and again, in multiple guises, far into the foreseeable future," write the authors.

 

 

While certainly not in the same league, a little over 3 months ago (on the day we first learned of the emergence of the H7N9 virus) I penned my own Brief History Of H7 Avian Flu Infections, which you may wish to revisit.

mBio: Taubenberger et al. On the 1918 Spanish Flu

Credit CDC PHIL

 

 

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mBio, the American Society for Microbiology’s online, open access journal, has published a long and fascinating review this morning on what we’ve learned over the past 15 years about the 1918 H1N1 `Spanish Flu’ pandemic virus, written by some of the biggest experts in the field.

 

At this point, I’ll just step aside and invite you to read:

 

 

Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past

 

Jeffery K. Taubenberger, David Baltimore, Peter C. Doherty, Howard Markel, David M. Morens, Robert G. Webster and Ian A. Wilson

 

doi:10.1128/mBio.00201-12

 

Highly recommended.

Morens and Taubenberger: A New Look At The Panzootic Of 1872

 

 

 

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One of the most fascinating events in relatively modern infectious disease history occurred in the fall of 1872, when a massive wave of (presumably) equine influenza swept across North American, infecting much of the horse population from Canada to Mexico – and killing up to 10%.

 

You’ll find an excellent history of this outbreak from Horsetalk.co.nz.

 

How equine flu brought the US to a standstill

A Boston fire wagon without its horses.

September 26, 2007

 

Australia's equine flu outbreak may have crippled the racing industry, but an 1872 outbreak in North America brought the entire US economy to a virtual standstill.

(Continue . . .)

 

 

This was at a time in history when horses were the primary means of transportation, and the economic effects of this months long epizootic were substantial, and some have suggested it contributed to the economic Panic of 1873 the following year.

 

Ian York author of the Mystery Rays blog wrote about this incident back in December of 2009 in a blog called Influenza before 1918, part II: 1872.  A brief excerpt:

 

Without horses, business slammed to a halt; the mail didn’t run, groceries didn’t reach the cities, crops weren’t harvested or transported.  After a few weeks, most of the horses recovered and business followed, but the epizootic swept across the country (intensely tracked by the newspapers of the day, warning each city in turn that it was going to be attacked), finally fizzling out the following summer in British Columbia.

 

Little remembered today, this was a huge story in 1972.  The assumption has been that this was sparked by some drift or shift in an already existing equine influenza.

 

But David Morens and Jeffrey K. Taubenberger of the NIH bring us tantalizing details of a concurrent outbreak of poultry deaths across the country, and that raises some interesting questions.

 

Without the ability to analyze and identify pathogens from that era, researchers are understandably hampered in their understanding of what exactly what transpired 140 years ago.  

 

But Taubenberger and Morens discuss a plausible scenario where a highly pathogenic avian virus may have jumped species and infected horses, pigs, deer, and in some cases, even humans.

 

My thanks to mixin on FluTrackers for posting this link.

 

Morens and Taubenberger (2010) An avian outbreak associated with panzootic equine influenza in 1872: an early example of highly pathogenic avian influenza? Influenza and Other Respiratory Viruses 4(6), 373–377.

Abstract

Background An explosive fatal epizootic in poultry, prairie chickens, turkeys, ducks and geese, occurred over much of the populated United States between 15 November and 15 December 1872. To our knowledge the scientific literature contains no mention of the nationwide 1872 poultry outbreak.

Objective To understand avian influenza in a historical context.

Results The epizootic progressed in temporal-geographic association with a well-reported panzootic of equine influenza that had begun in Canada during the last few days of September 1872. The 1872 avian epizootic was universally attributed at the time to equine influenza, a disease then of unknown etiology but widely believed to be caused by the same transmissible respiratory agent that caused human influenza.

Conclusions Another microbial agent could have caused the avian outbreak; however, its strong temporal and geographic association with the equine panzootic, and its clinical and epidemiologic features, are most consistent with highly pathogenic avian influenza. The avian epizootic could thus have been an early instance of highly pathogenic avian influenza.

 

 

Jeffrey  K. Taubenberger and David Morens are, of course,  familiar names to followers of influenza and virology.

 

Both are researchers at NIAID. Taubenberger, quite famously, was the first to sequence the the genome of the 1918 Spanish Flu virus while David Morens is a prominent medical historian and professor.

 

Both are extensively published, and have collaborated often in the past.

 

As this report is too good to try to summarize, I’ll simply suggest you follow this link and read it in its entirety.

Morens, Taubenberger & Fauci: What’s Next For H1N1

 

 

 

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In an open access perspective article appearing in the journal mBio, well known NIH scientists and researchers David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci give their take on the future of the novel 2009 H1N1 virus.

 

 

The 2009 H1N1 Pandemic Influenza Virus: What Next?

1. David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci

ABSTRACT

History suggests that the 2009 pandemic H1N1 influenza virus faces extinction unless it mutates to avoid already high global population immunity. The immune escape mechanisms potentially at its disposal include antigenic drift, antigenic shift via genetic reassortment, and intrasubtypic reassortment.

 

Going back to the late 19th century, the evolutionary histories of past pandemic viruses are examined in an effort to better understand the nature and extent of the immune pressures faced by the 2009 pandemic virus in the immediate future.

 

While human influenza viruses have often surprised us, available evidence leads to the hope that the current pandemic virus will continue to cause low or moderate mortality rates if it does not become extinct.

 

The FULL TEXT is available here.

 

For those who prefer the Press Release condensed version, we have that as well:

 

NIH scientists consider fate of pandemic H1N1 flu virus

Whither pandemic H1N1 virus? In a new commentary, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, review the fates of previous pandemic influenza viruses in the years following a pandemic and speculate on possible future courses for the 2009 pandemic H1N1 (pH1N1) virus during the upcoming flu season and beyond.

 

The authors estimate that at least 183 million Americans (about 59 percent of the total U.S. population) have some immunity to pH1N1 because they were exposed to related viruses or vaccines prior to 2009, were immunized against pH1N1 or developed immunity following infection with the pandemic virus.

 

To stay in circulation in the face of such high levels of population immunity, the pH1N1 virus must adapt either through abrupt or gradual changes. The authors briefly examine a number of earlier pandemics and trace paths taken by the causative viruses. Some—for reasons not well understood—died out, while others, like those of 1889 and 1918, returned in an explosive fashion. Such an explosive return of pH1N1 virus is unlikely, note the authors, because global levels of immunity are already high and will increase further through immunization with 2010-2011 seasonal influenza vaccines, which contain the pH1N1 strain.

 

In light of what is known about pH1N1, the NIAID authors express a cautious optimism that unless it disappears entirely the virus will follow a route like that of 1968 pandemic virus, that is, it will persist in a form that causes relatively few deaths.

 

Nevertheless, the authors caution against complacency. As they acknowledge, many gaps remain in understanding how a given pandemic influenza virus adapts to increased immunity in humans. For that reason, influenza vaccination for everyone older than six months is a wise public health measure to maintain high levels of population-wide immunity. Immunization with 2010-2011 seasonal flu vaccine is particularly urged for babies older than six months, children, teens and young adults as the best way to protect individuals in those potentially more susceptible age groups from illness.