Controversial flu paper finally published

It's been a long time since I've blogged an article. I've been super busy with my assignments and exams for my masters and I'm finally more free to do my thesis. Here's an interesting read this morning on a recent controversial H5N1 flu virus research paper:

"One of two controversial studies of H5N1 bird flu, held back because of fears about bioterrorism, has finally been published. The work, by Yoshihiro Kawaoka and colleagues at the University of Wisconsin-Madison, was considered the less threatening of the two studies, partly because it created a virus that did not kill the experimental subjects – ferrets.

Kawaoka's work could help the world guard against bird flu by showing what kinds of changes in the virus – not just which particular mutations – could lead to an H5N1 pandemic.

Both the Kawaoka work and the study by Ron Fouchier and colleagues at Erasmus Medical Centre in Rotterdam, the Netherlands, show that H5N1 can evolve to spread between mammals. As such, they confirm that H5N1, now spreading across Eurasia and in Egypt, does present a real pandemic threat.

Bioterrorism fear

Full publication of both studies was delayed after US biosecurity experts said the studies were recipes for bioweapons – a decision revised last month.

The US committee unanimously agreed that there was little threat in Kawaoka's virus, although if it got loose it could potentially unleash a whole new human flu family. Kawaoka's research paper, which appears this week in the journal Nature, is accompanied by a "risks and benefits" assessment by what the journal describes as "a bio-defence agency outside the US". The assessment argues that safety measures were adequate and the benefits of the research were worth the risks.

The US committee was divided over the Fouchier study, though, because that adapted virus did kill ferrets. The debate over the Fouchier study also led to its falling foul of Dutch export restrictions on sensitive material. Fouchier, objecting to the idea of trade officials controlling the publication of research, briefly threatened last month to publish without permission from the Dutch government, which might have left him facing criminal charges. But he relented, the government gave permission, and the work should appear shortly in the journal Science.

In Kawaoka's study, only the surface protein – haemagglutinin (HA) – was from H5N1. The rest was 2009 pandemic flu, which does not kill ferrets. Both the 2009 virus and H5N1 infect pigs, though, and a hybrid of the two could emerge naturally, making it valuable to know how such a virus might behave.

The work shows that before a hybrid could spread in people, the HA would have to change. Kawaoka's team gave it two mutations that boosted binding to sugars on human, rather than bird, throat cells. It picked up two more mutations while infecting ferrets, which let it grow faster. Viruses with all four spread via airborne droplets between ferrets as readily as the deadly 1918 pandemic virus.

Wild mutations

Both the Wisconsin and Rotterdam viruses have four mutations in their HA, but not all of these mutations are the same in the two viruses.

Kawaoka's team says its study should permit virologists to recognise viruses that pose a pandemic threat, even if they have different mutations. This is because the mutations that allowed the team's virus to spread had particular chemical effects on HA. They boosted binding to the human sugar; they made HA less sensitive to acid, which triggers a radical shape-shift in the protein during the infection process; and they prevented a crucial chemical process called glycosylation, in which a carbohydrate is attached to the HA protein at one spot, changing the shape of a cleft in the molecule where it binds to a cell to infect it. Several mutations have these effects, so any of them could be dangerous.

It is not clear how many such mutations are already circulating in the wild. But mutations that prevent the crucial glycosylation "are not uncommon in the field, in both avian and human H5N1 viruses", says Malik Peiris, a leading flu virologist at Hong Kong University.

Peiris is co-author of a review also published this week in Nature that compares the dozen or so studies so far that have explored mutations and transmission in H5N1. Only the Rotterdam and Wisconsin studies have been held up for biosecurity concerns.

Journal reference: Nature, DOI: 10.1038/nature10831"

Acknowledgement: http://www.newscientist.com/article/dn21773-controversial-flu-paper-finally-published.html 

Well, I was thinking, if glycosylation is such an important process which changes the binding site on the molecule, perhaps a therapeutic potential would be to glycosylate this site? However, glycosylation of proteins in an post-translational process in humans, so how do we ensure proper targeting of the carbohydrate to HA? Maybe an alternative form of carbohydrate that will not be used by humans and only by the virus? 

That's something to think about.