One of the two controversial papers on bird flu, put on hold for a few months, gets published

At last, the controversial paper by Yoshihiro Kawaoka of the University of Wisconsin-Madison on mammalian transmissibility of H5N1 (bird flu) virus through genetic manipulation is published today (May 3) in Nature.

The study looks at droplet transmission of the virus in a ferret animal model. Ferrets are chosen for such studies as they are the best animal models that mimic human influenza effects.

The “principal scientific interest” of the study “arises from the small number [four] of mutations found to be necessary” to make it transmissible, notes the Editorial accompanying the piece. The findings also clearly indicate that the viruses have potential to cause a “human pandemic.”

And it was precisely for this reason that the paper, which was submitted to the journal in August 2011, faced many hurdles. The US National Science Advisory Board for Biosecurity (NSABB) wanted the journal to publish only a redacted (censored) version as it feared that the details in the paper could be used by some people for engaging in bio-terrorism. The NSABB finally cleared the full publication of the paper in March end.

The procedure

Dr. Kawaoka first introduced four mutations into the viral haemagglutinin (HA) protein of H5N1. He then combined the H5N1 virus with seven gene segments from the 2009 pandemic H1N1 (swine flu) virus.

Genes of influenza virus strains from one source (man/animal) combining with another animal occurs continually in nature, and the resultant virus is called a reassortant influenza virus.

The reassortant virus that Dr. Kawaoka and his team produced was capable of droplet transmission. It was able to replicate “efficiently” in ferrets but did not kill them. Also, the virus “preferentially recognised human-type receptors.” It is worth noting that the binding of H5N1 virus to avian cells is very different from the way human influenza binds to human cells.

Occurs in nature

“Natural emergence of an H5N1–H1N1 hybrid [reassortant] virus is plausible. Some H1N1 and H5N1 viruses readily swap genes with one another in vitro, generating hybrid viruses, states a News and Views piece accompanying the paper. “Pandemic H1N1 viruses are established in pigs in many parts of the world, and H5N1 viruses have been isolated from pigs, suggesting that opportunities exist for the viruses to combine in these animals.”

Why the concern

The team led by Dr. Kawaoka states that “recent studies” have shown “high genetic compatibility” between the pandemic H1N1 virus and the avian H5N1 virus. “These two viruses have been isolated from pigs, which have been considered as ‘mixing vessels' for the reassortment of avian, swine and human strains,” they write. Their very presence together in pigs provides an ideal opportunity for transmissible H5N1 reassortants to emerge.

Bird flu outbreaks in poultry occur quite frequently, and in some instances, such as in Indonesia, Vietnam and Egypt, transmission to humans has been reported. But H5N1 is yet to acquire the ability to become transmissible from one human to another.

Humans “lack immunity” to H5N1 mutant viruses, and hence the possibility of a H5N1 pandemic cannot be ruled out. Hence it is “critical” to understand the “molecular changes” that might take place in the viral haemagglutinin (HA) protein that will make H5N1 virus transmissible in humans, they note.

The only way of staying prepared of such an eventuality is by knowing in advance the possible mechanism required for the emergence of such a strain. Though it is not clear if four mutations alone would have made the avian H5N1 virus transmissible, the study provides a window to the several possibilities.

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