Researchers Find New Details on Transmission of Avian Flu

Two groups of researchers, in Japan and in Holland, have discovered why the avian flu virus is transmitted rarely if ever from one person to another.

The reason is simply that the cells bearing the type of receptor the avian virus is known to favor turn out to be clustered in the deepest branches of the human respiratory tract. The viruses thus cannot be spread by coughs and sneezes, as are human flu viruses which infect cells in the upper respiratory tract.

The avian flu virus would need to accumulate many favorable mutations in its genetic material before it could become a pandemic strain, said Yoshihiro Kawaoka, a virologist at the both the University of Tokyo and the University of Wisconsin. According to a press statement he approved, "The finding suggests that scientists and public health agencies worldwide may have more time to prepare for an eventual pandemic."

Dr. Kawaoka's finding is published in today's issue of Nature and a similar finding, by Thijs Kuiken and colleagues of the Erasmus Medical Center in Rotterdam, appears in this week's Science.

Flu experts already knew that those attacked by the current avian flu virus, a type known as H5, were infected in the lower lung.

Paul Offit, a virologist at the Children's Hospital of Philadelphia, said the new reports made a lot of sense in explaining why the H5N1 virus, though it can infect people, does not easily spread from one person to another, making its outbreaks very limited.

Virologists agree that another flu pandemic will happen sooner or later as one of the 16 types of flu virus in the animal world, probably one that infects birds, will manage to switch hosts and grow and spread in humans. But they differ as to whether H5 is the likeliest candidate to make this switch. Previous known pandemics have been caused by H1 type viruses (the 1918 pandemic), H2 (the 1957 Asian) or H3 (the Hong Kong flu of 1968).

The H5 strain of avian flu has been infecting people since the late 1950's but has so far failed to develop a form that is easily transmissible from one person to another. Some virologists believe it could easily do so because it may only need better transmissibility to set off a pandemic. That could be obtained simply by switching its preference from the cell receptor found in the lower lung, known as alpha 2-3, to the receptor found on cells in the upper airways, known as alpha 2-6.

A team of scientists at the Scripps Research Institute reported in Science last week that only a couple of mutations might be needed to enable the H5 virus to make this switch to the alpha 2-6 receptor. This is about the same number of mutations as made by the H1, H2 and H3 viruses when they learned to infect people. Since viruses mutate quickly, a two-mutation step is not so big a hurdle.

Because the H5 virus has killed about half of the 187 people it has so far infected, "a lot of its genes are already optimized for virulence," said James C. Paulson, a member of the Scripps team. For H5 to become pandemic, "The key gene that needs to be mutated is the HA gene," he said, referring to the hemagglutinin gene, which makes the probe used by the virus to latch on to a cell's receptor sites.

But though H5 might seem only a couple of easy steps away from transmissibility among people, many virologists believe mutations in several other genes would be necessary as well. Viruses find it very hard to switch hosts, and though they may quite often cause outbreaks in just a few individuals, "viruses that produce a self-sustaining chain of transmission in the new host appear rare," Dr. Kawaoka wrote recently in the Annual Review of Microbiology,

The H5 virus has been present in the human population since the late 1950's, but has never acquired the full set of mutations needed to set off a pandemic. The epidemiological evidence "should make us feel safe that there's a substantial barrier," Dr. Offit said.

Dr. Offit said it was a good thing to worry about the next pandemic, given that about three can be expected every century. "What's not good is to try to sell the public on their fear of pandemic flu being this particular bird flu, since if it's not, crying wolf will lose you credibility," he said.

Peter Palese, a virologist at the Mount Sinai School of Medicine, said he did not believe the H5 virus could infect people, except when they were exposed to very large doses, such as by sleeping with chickens in the same room. "I feel strongly that H5 has been around in humans for a long time and never caused a pandemic, suggesting that this is not the virus which is likely to be the next pandemic."

But like Dr. Offit, Dr. Palese said he fully supported plans to get better prepared for the next flu pandemic. "People have to understand we are not really prepared should it come," he said.