Scientists Create Hybrid, Air-Transmissible Bird Flu Strains

Following a moratorium on "dangerous" flu research, new studies reshuffle the molecular mechanisms that allow bird flu to infect humans.

The most recent bird flu strain claimed another victim today, bringing the number of dead to 27, all in China. So far 127 people have fallen ill, and world health authorities say the new H7N9 flu is a global threat that should be taken seriously. The strain, which has been transmitted from chickens to humans, is so far unable to move from person to person. But scientists are figuring out how other strains could.

The journal Science is publishing two papers today that describe the mechanisms avian flu viruses could use to alter their structure and spread among mammals, including humans. One of the papers studied guinea pigs, which are not necessarily the best way to study the human response to flu—but studies on ferrets, which are a good proxy for people, were halted by a year-long moratorium. That hiatus recently ended, so more papers in this vein are likely to follow.

Some scientists are decrying the research as potentially dangerous—”appallingly irresponsible,” in the words of Lord May of Oxford, a former government chief scientist and past president of the UK’s Royal Society.

Fears of viruses escaping into the wild were the main motivation behind the voluntary moratorium scientists imposed last year, which halted research on making bird flu airborne. Virologists got back to work in January, saying the benefits outweigh the risks and promising safeguards that will protect lab workers and the public. This new research could very well re-ignite that debate.

But like other researchers before them, these authors argue their experiments, one of which deliberately mixes swine flu and bird flu, are crucial for understanding the way flu viruses spread.

Ying Zhang, Hualan Chen and colleagues at the Chinese Academy of Sciences combined genetic material from bird and human flu viruses, demonstrating how they might re-assort their genes and mix together. This could explain how bird flu viruses could naturally mix with human viruses—for instance, swapping their human airway proclivity and their propensity for spreading. The team mixed together the notorious 2009 “swine flu” H1N1 variant and a H5N1 variant that can spread among guinea pigs. They came up with 127 different virus combos, some of which were able to spread through the air.

The airborne viruses were not lethal. That’s been the case each time scientists mutate bird flu viruses to become airborne and infect mammals. But critics say the research is still highly dangerous.

Another paper also in Science sheds more light on these processes. Wei Zhang and colleagues, also at the Chinese Academy of Sciences, studied the molecular means the flu virus would use to infect humans. Flu strains get their name—H5N1, H7N9—from their molecular components: H5N1 flu, for example, is a variant with type 5 hemagglutinin and type 1 neuraminidase, which are proteins. These proteins bind to a receptor in the airway of the host, and usually, these receptors and binding agents are species-specific.

For instance, humans have no immunity to flu viruses with a type 5 hemagglutinin, but this type of flu also doesn’t bind to human air passages. Previous work has shown that it can mutate to become transmissible through the air among ferrets (although the ways in which researchers achieved this are not analogous to what would happen naturally). The mutations involved changes in a gene called HA, which binds the virus protein to the air passages. But scientists were not sure how these changes occurred.

Wei Zhang and colleagues set out to solve this question. It turned out to have a somewhat simple answer: The atoms in the human-adapted strain of H5N1 avian flu had a slightly different arrangement. In what may be a good sign, the mutated strain also was less likely to cause serious infection than its wild, un-mutated cousin. Something about the switch to a human-preferred protein shape seems to make the virus less effective.

This is also interesting for the H7N9 strain, according to the paper—it turns out that H7N9 has a particular amino acid substitution, called Q226L, that was necessary to make the avian flu into a human flu. The fact that H7N9 has it naturally, rather than induced through a mutation, could help explain why that particular strain has a higher infection rate in people right now.

It’s also important to note that guinea pigs actually have some avian-like receptors in their respiratory tracts, which make them susceptible to bird flus in a way that humans are not. The next step would be to test these experiments using ferrets, which are a better model for how the flu works in people.