Two genetic changes – bird flu becomes pandemic

Given all the uproar over H1N1 (‘swine flu’), does anyone remember H5N1? That’s ‘bird flu’ and only a couple years ago it was the bête noir of the world’s health organizations. Fortunately, although deadly (roughly a 60% fatality rate), bird flu was not readily transmitted human-to-human. Now we know why: It would need to make two genetic changes before it would become much more infectious for humans.

The bird flu garnered much media attention (it’s tempting to say hype), which in a sense ‘fizzled’ because in the end ‘only’ about 400 people contracted the disease. It was clearly not a real pandemic and health organizations collectively sighed relief. But that is not the end of the story. Viruses are notorious for adaptability. Today’s meek and mild infection, can, no-thanks to a mutation or two, become tomorrow’s killer. Or vice versa. The issue for science and medicine is to try to understand what is happening at the molecular level. What causes a virus to become deadly, or transmittable?

To infect a cell, the influenza virus uses a protein called HA to attach itself to a receptor molecule on the cell’s surface. However, it can only do this if the HA protein fits that particular receptor. Today’s research shows that H5 would only be able to make this kind of adaptation and fit the receptor on the cells that are important for virus transmission if it went through two simultaneous genetic mutations.

Professor Wendy Barclay, corresponding author of the study from the Division of Investigative Science at Imperial College London, said: “H5N1 is a particularly nasty virus, so when humans started to get infected with bird flu, people started to panic. An H5N1 pandemic would be devastating for global health. Thankfully, we haven’t yet had a major outbreak, and this has led some people to ask, what happened to bird flu? We wanted to know why the virus hasn’t been able to jump from human to human easily.

The researchers used a realistic model of the inside of a human airway to study H5 binding to human cells. They made genetic changes to the H5 HA protein to change its shape, to see if they could make the virus recognise and infect the right types of cells. Results showed that the virus would need two genetic changes occurring at once in its genome before it could infect these cells.

The authors of the new study, from Imperial College London, the University of Reading and the University of North Carolina, USA, argue that it is very unlikely that two genetic mutations would occur at the same time.

[Source: EurekAlert]

Of course, when it comes to virus mutation, unlikely is anything but impossible. That’s why studies like this one are valuable. It not only points out why a pandemic didn’t occur but also suggests what a vaccine should do, if the dreaded mutations take place.

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