How bird flu spreads

Jay Fitzsimmons
Published in Sept 2006 issue of The Windsor Scoop. Reposted here with permission.

Bird flu was hot last year. Not since R2-D2 and C-3PO has a jumble of letters and numbers been as famous as H5N1. You couldn’t turn on a television without hearing how bird flu could be the next pandemic, killing millions of people worldwide. Not that I’m complaining, but why hasn’t that happened yet?

Several research articles have been published in the journals Science and Nature this spring that improve our understanding of the H5N1 bird flu virus. The findings suggest why it is hard for humans to catch, why it has trouble spreading between humans, and how the virus could mutate to live up to the dire predictions.

Birds vs. humans

First, a brief lesson on bird guts and human lungs. H5N1 normally infects cells lining the bird digestive system. The cells in bird digestive system have receptors with (-take a deep breath-) complex glycans terminating in sialic acid α2-3 linked to a vicinal galactose. I’ll call these receptors α2-3 for short. Normally a flu virus can only infect a specific type of cell, but H5N1 can infect intestine cells, lung cells, and more.

The H5N1 virus only binds to α2-3 receptors, while human flu viruses bind to α2-6 receptors. Different scientists have now found, and reported in both Science and Nature, that α2-3 and α2-6 receptors line different parts of our respiratory system. Much of our upper respiratory system (such as the throat) has α2-6 receptors. Those α2-3 receptors that are in our upper respiratory system occur on mucins, the source of mucous. However disgusting mucousy phlegm may seem, it serves a very important purpose: it collects viruses and other particles, preventing them from entering our lungs. Our lower respiratory system has unprotected cells with α2-3 receptors, but to get to them a virus has to run the mucin gauntlet. This provides a simple reason why it is hard for humans to catch bird flu: the cells with receptors to which H5N1 virus binds are hard to get to. People who have caught H5N1 generally live or work in close quarters with birds, so swarms of H5N1 virus likely overwhelm the mucin gauntlet. Cats have a similar respiratory system to humans, and catch H5N1 and exhibit symptoms similar to humans.

Despite over 200 cases of H5N1 in humans, there has only been one case of probable human-to-human transmission (Pranee Thonchan of Thailand, while caring for her sick daughter, both of whom died within days). The obstacle to human-to-human transmission of H5N1 is likely that infected α2-3-receptor cells are deep in our lungs. Normal human flu viruses spread through sneezes and coughs showering the air with fine particles, including viruses, from the top of our respiratory system. H5N1 infects cells too deep in the lungs of humans to be spread effectively from sneezes.

Deep-lung infection of H5N1 also explains its symptoms in humans and its high mortality rate. Death from H5N1 is painful, involving normal human flu symptoms magnified in severity. Between the accumulation of debris from virus-killed lung cells and the body overwhelming the infection with anti-viral fluids, lung spaces flood. Effectively, people suffocate. This deep-lung effect of H5N1 makes sense in light of it infecting cells deep in our lungs.

H5N1 evolution

Can H5N1 evolve to bind to human α2-6 receptors? Yes. How quickly? Nobody knows – maybe never. There are several barriers to any virus transferring between host species, in this case from bird to humans, and spreading among the new species. Unfortunately several of those barriers have already fallen for H5N1. Poultry and humans both live at higher densities than ever before, allowing possible spread at unprecedented speed. Recent years have seen a mutation to H5N1 that allows it to take over human cell processes, which it could not do before. Research published in an April issue of Science found that a single mutation could allow H5N1 to bind to a certain type of human α2-6 receptor. Viruses evolve quickly, and several in the past have evolved to switch from α2-3 to α2-6 receptors, such as an H1-series virus did in 1957. Evolution to bind to α2-6 receptors could take place in cats, quails, or other animals infected with the virus that have both α2-3 and α2-6 receptors. Any mutation that allows the virus to bind to α2-6 receptors could allow that virus to spread, and increase in numbers as it infects more hosts (which, to any creationists out there, is evolution). Drugs against such a new strain of H5N1 cannot be made until the mutations occur, when the nature of the strain is known.

Should I eat chicken?

According to the World Health Organization (WHO), “properly cooked poultry and poultry products are safe to eat.” No human infections have been proven to originate from eating infected poultry. But, as one Japanese virologist recently stated in a column in the journal Nature, “direct evidence of oral infection is lacking, but so too is proof against.”

Many virologists and researchers, including some WHO consultants, are reluctant to exonerate food as a potential source of infection. The source of many human infections is unknown, so we can’t say it was not from food. Cats, whose human-like respiratory infection of H5N1 makes them “the most suitable animal models for human H5N1 viral pneumonia” according to an April article in the journal Science, are frequently infected from eating infected birds. From domestic cats in research laboratories to tigers and leopards in Thai zoos, many cats have been infected and died from eating infected bird meat. Is our digestive system less susceptible to infection than that of cats? We don’t know, but evidence suggests not. People infected with H5N1 excrete the virus with feces through the intestinal system, and autopsies of human victims of H5N1 reveal infection along intestinal tracts. So H5N1 can infect our digestive system cells, we just don’t know whether an infection can start there from infected food. Will cooking meat kill the virus? Yes, just as cooking kills Salmonella bacteria. But we know from modern infections of Salmonella that people take shortcuts in the kitchen, such as re-using knives that have cut raw chicken.

Should the WHO state it doesn’t know whether eating infected meat and eggs is dangerous? Such a statement may provoke consumers to turn away from chicken and eggs en masse, devastating many people involved in poultry industry worldwide. If there is indeed no danger of infection from food, peoples’ lives would be ruined for nothing. But if there is a danger, then people will be upset with WHO for not stating the risks earlier. The WHO is in a difficult position.

My goal is not to frighten you, but to inform you. The public and experts alike have many questions about H5N1. From doctors treating patients in Egypt, to molecular researchers studying possible mutations, to government officials predicting consequences of a pandemic, we are trying to understand the beast. It is useful to keep in mind that no cases of H5N1 have been reported in Canada, in any animal. Our chicken meat and eggs are safe to eat. It is also useful to recall that H5N1 cannot yet spread between people effectively. It remains, at its heart, a bird virus. We are relatively safe – for now.

For more information:

WHO website:
BirdFlu by John Farndon, a new arrival to Windsor Public Libraries