Avian flu viruses mutating, making humans more vulnerable: study

North American avian flu viruses of the H7 subtype — like the H7N3 viruses responsible for British Columbia's massive poultry outbreak in 2004 — seem to have adapted to more easily invade the human respiratory tract, a new American study suggests.

The adaptation is still only partial and the findings do not suggest the viruses are imminently poised to trigger a pandemic. But experts say they underscore the fact that H7 flu viruses need to be watched and studied.

"I think this is certainly amongst the most dangerous [avian flu] viruses out there," said virologist Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands.

"And I think we need to continue to develop vaccines for H7 just as well as H5(N1)."

Fouchier was commenting on a scientific paper published Monday by the journal Proceedings of the National Academy of Sciences.

Fouchier's research on avian influenza includes study of the H7N7 outbreak in the Netherlands in 2003, but he was not involved in this work.

Scientists from the U.S. Centers for Disease Control reported on their research on a number of H7 viruses, looking both at the types of receptor cells — bird or human — each was more inclined to latch onto and whether the viruses transmitted from infected to uninfected ferrets.

Of all available animal models, influenza infection in ferrets is considered to mirror most closely the course the disease takes in humans.

Human flu viruses that circulate every winter have adapted to be able to bind to the receptors that predominate in the human respiratory tract, known as alpha 2-6 receptors. Avian viruses, on the other hand, prefer the alpha 2-3 receptors found in the guts of wild birds (their natural host) and domestic poultry. Those receptors are scarce in the human upper respiratory tract.

It is assumed that an avian virus would need to make this kind of adaptation — learning to latch onto the human-type receptors — before it could transmit easily to and among humans.

Among the H7 viruses the CDC scientists studied were H7N3 viruses recovered from the two British Columbians infected during an outbreak in the poultry farm-dense Fraser Valley in 2004. More than 17 million chickens were destroyed in the efforts to stop that outbreak.

Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.

Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.

Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.

But in general H7 viruses from North America that have been isolated from about 2002 onwards seem to have developed an increasing affinity for the human-type receptors, said Dr. Terrence Tumpey, the CDC scientist who led the work.

"These viruses are partially adapted to recognize the receptors preferred by human influenza viruses, but not completely," he said in an interview from Atlanta.

"It needs to be adapted further. But I think it shows that potentially that these viruses are changing.

"Because we can look at an older North American H7 or Eurasian H7s or H5s and they have the characteristic avian influenza binding properties. Whereas these seem to be different and possibly changing."

At this point it is unclear what additional changes would be needed for an H7 virus to fully adapt to a human host — or whether H7 viruses could acquire all those changes.

When H7 viruses have caused human cases, the ensuing disease has typically been mild, with people suffering conjunctivitis (pink eye) and-or mild respiratory symptoms. There is one exception — a veterinarian infected with an H7N7 virus died during the Dutch outbreak.

The mildness of the disease may have lulled some people into a sense of complacency about H7 viruses, said Dr. Danuta Skowronski, an influenza expert at the British Columbia Centre for Disease Control. 

But she insisted the fact that H7 viruses don't induce the life-threatening disease seen in H5N1 infection doesn't mean they shouldn't be viewed as a serious pandemic threat.

"H7, with its mildness, may be more — I hate to anthropomorphize — but more devious. Because through surreptitious spread — because it's milder, it's unrecognized, people might dismiss it more — it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver. 

"And even though it may be mild today, even though it may not transmit easily today, the potential is always there for it to change. And basically we don't want new [flu] subtypes in the human population. We've got enough to deal with the humanized strains."