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Controversial avian flu paper that raised bioterrorism fears finally goes to press


May 3, 2012 - London

After an epic debate over a pair of studies that reveal how the avian H5N1 influenza virus could become transmissible in mammals, and an unprecedented recommendation by a government review panel to block publication, one of the studies was finally and fully published on Thursday.

Publication caps an epic public conversation that pitted some infectious diseases experts against flu and public health researchers who argued that publication was not only important, but also essential to informing influenza surveillance and preparedness for a virus that could evolve to infect humans and cause a global pandemic.

The research was one of two experiments that a federal advisory panel had asked journals to hold off publishing because the papers might provide a how-to guide for terrorists or mischief-makers, the Washington Post reported.

Later, the panel dropped its objections after it became evident that the engineered viruses were less virulent than had been feared.

"Our study shows that relatively few amino acid mutations are sufficient for a virus with an avian H5 hemagglutinin to acquire the ability to transmit in mammals," said Yoshihiro Kawaoka, a University of Wisconsin-Madison flu researcher whose study of H5N1 virus transmissibility was at the center of the debate.

"This study has significant public health benefits and contributes to our understanding of this important pathogen. By identifying mutations that facilitate transmission among mammals, those whose job it is to monitor viruses circulating in nature can look for these mutations so measures can be taken to effectively protect human health."

However, Kawaoka cautions there may be other unknown mutations that also enable the virus to transmit in mammals. It is therefore critical, he argues, to continue research to identify additional mutations that have the same effect, and to understand how they work.

The study, conducted by an international team of researchers led by Kawaoka, a UW-Madison professor of pathobiological sciences and a leading expert on influenza, shows that some viruses now circulating in nature require just four mutations to the hemagglutinin protein, which sits on the virus surface and enables it to bind to host cells, to become an even greater threat to human health.

A subset of the mutations identified by the Wisconsin group has, in fact, already been detected in some viruses circulating in poultry flocks in Egypt and parts of Southeast Asia, underscoring the urgency of science-based surveillance, Kawaoka said.

Kawaoka's group described a laboratory-modified bird flu/human flu hybrid virus that can become transmissible in an animal model for human infection with just a handful of mutations.

Because flu viruses in nature are constantly changing as they circulate and easily swap genes with other flu viruses, the possibility of circulating H5N1 viruses hitting the right combination of mutations and becoming a much bigger threat to human health is greater than many experts believed, avers Kawaoka, a faculty member in the UW-Madison School of Veterinary Medicine.

"H5N1 viruses remain a significant threat for humans as a potential pandemic flu strain. We have found that relatively few mutations enable this virus to transmit in mammals. These same mutations have the potential to occur in nature," explained Kawaoka.

In addition to demonstrating transmissibility, Kawaoka's results showed the experimental mutant virus could be controlled by available medical countermeasures. An H5N1 vaccine as well as oseltamivir, an antiviral drug better known by the trade name Tamiflu, both proved effective.

Whether or not the H5N1 viruses currently circulating in the world can easily acquire the additional mutations needed to cause a pandemic is an open question, according to Kawaoka.

"It is hard to predict. The additional mutations may emerge as the virus continues to circulate."

The new work will aid those who monitor flu and could provide a critical early warning.

"Should surveillance activities identify flu strains accumulating additional key mutations, these emerging viruses should then be priority candidates for vaccine development and antiviral evaluation," added Kawaoka.

One important upshot of the study by Kawaoka's group is the identification of the mechanism by which the H5N1 virus transmits, a basic discovery that could aid in the development of countermeasures, and that contributes to the store of basic knowledge on influenza virus transmission.

The study has been published in the journal Nature.

ANI

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