Wednesday, May 02, 2012

Nature Publishes The Kawaoka H5N1 Study



BSL-4 Lab Worker - Photo Credit –USAMRIID


# 6312



Although it was Ron Fouchier’s announcement last September (see New Scientist: Five Easy Mutations) of his successful manipulation of the H5N1 virus to make it transmissible among ferrets that set off biosecurity alarm bells (see NPR: Bio-Terrorism Concerns Over Bird Flu Research) and instigated an international debate, in a laboratory halfway around the world Dr. Yoshiro Kawaoka was quietly duplicating the feat.


Today (the embargo having lifted at 1pm) the journal Nature publishes Kawaoka’s study, which details how he created a modified H5N1 – H1N1 hybrid that transmits via respiratory droplets among ferrets.


While its virulence in ferrets was reduced over that of its parental H5N1 virus (exactly why is unknown), the big news is that it only took the introduction of 4 mutations into the H5N1’s hemagglutinin (HA) to allow it to bind efficiently to the alpha (2-6) sialic acid receptors found in ferret (and human) upper respiratory tracts.


Three of these mutations were directly involved in the binding to the a2,6 receptor cell, while the 4th stabilized the virus to fuse with receptor cells at pH levels typically found in the upper respiratory tract. 


An affinity for a2,6 receptor cells has long been thought vital for the virus to adapt to humans, but this 4th mutation - that facilitates virus-cell fusion - may prove equally important.


Given its highly public and bumpy road to publication, Kawaoka’s study (see below) is certain to receive an inordinate amount of scrutiny and review over the next couple of days.



Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to areassortant H5 HA/H1N1 virus in ferrets



Masaki Imai, Tokiko Watanabe, Masato Hatta, Subash C. Das, Makoto Ozawa, Kyoko Shinya, Gongxun Zhong, Anthony Hanson, Hiroaki Katsura, Shinji Watanabe, Chengjun Li , Eiryo Kawakami , Shinya Yamada, Maki Kiso5,Yasuo Suzuki , Eileen A. Maher, Gabriele Neumann & Yoshihiro Kawaoka


Kawaoka’s 11-page study is, as you might imagine, highly technical and may prove tough sledding for those without a solid background in virology.


Nature published a 2-page synopsis by Hui-Ling Yen & Malik Peiris that helps to explain some of the details, but this is a pay-to-view article.



Bird flu in mammals

An engineered influenza virus based on a haemagglutinin protein from H5N1 avian influenza, with just four mutations, can be transmitted between ferrets, emphasizing the potential for a human pandemic to emerge from birds. 



According to Malik Peiris, this study reaffirms the pandemic potential of the H5N1 virus, and reinforces the need for better surveillance of the virus in the wild.


While Kawaoka identified several mutations in the H5 HA that allowed the virus to bind to a2,6 receptors there are likely other combinations that could lead to greater transmissibility.


For the best all-around coverage of this story, we can always rely on Helen Branswell of The Canadian Press. Helen has just posted the following article on this research’s publication.



Bird flu study: Three mutations might give virus ability to transmit to humans

By: Helen Branswell, The Canadian Press



There will, undoubtedly, be a large number of stories and opinion pieces regarding the publication today of Kawaoka’s research.


Already I note  that Vincent Racaniello has blogged on this publication:


Kawaoka paper published on aerosol transmission of H5 influenza virus in ferrets

2 May 2012

Meanwhile Laurie Garrett  takes a more cautionary route in:


Manmade H5N1 Paper Finally Published, And Worrying



I’ll update this blog with more links to articles and opinion pieces on this research later today or tomorrow.