Why avian flu has not created a pandemic

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Research: Why avian flu has not caused a pandemic

//23 nov 2009

Avian flu viruses would have to make at least two simultaneous genetic mutations

before they could be transmitted readily from human to human, according to

research published in PLoS ONE.

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. The study adds

to our understanding of why bird flu has not yet caused a pandemic.

Earlier this year, the Imperial researchers also showed that avian influenza

viruses do not thrive in humans because, at 32 degrees Celsius, the temperature

inside a person's nose is too low.

Human to human transmission

This study suggests that one reason why H5N1 has not yet caused a pandemic is

that two genetic mutations would need to happen to the virus at the same time in

order to enable it to infect the right cells and become transmissible. At

present, H5 viruses can only infect one of the two main types of cell in the

mouth and nose, which is the ciliated cell. In order for H5 to transmit from

human to human, it would need to be able to infect the other, non-ciliated type

of cell as well.

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. The 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 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, " she said.

The odds

" Our new research suggests that it is less likely than we thought that H5N1 will

cause a pandemic, because it's far harder for it to infect the right cells. The

odds of it undergoing the kind of double mutation that would be needed are

extremely low. However, viruses mutate all the time, so we shouldn't be

complacent. Our new findings do not mean that this kind of pandemic could never

happen. It's important that scientists keep working on vaccines so that people

can be protected if such an event occurs, " added Professor Barclay.

Recombinant approach

Professor Ian , leader of the collaborating group at the University of

Reading, added: " It would have been impossible to do this research using

mutation of the real H5N1 virus as we could have been creating the very strain

we fear. However, our novel recombinant approach has allowed us to safely

address the question of H5 adaptation and provide the answer that it is very

unlikely. "

Vaccine development

In addition to explaining why bird flu's ability to transmit between humans is

limited, the new research also gives scientists a better understanding of the

virus. They believe that this could help the development of a better vaccine

against bird influenza, in the unlikely event that one was needed in the future.

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 researchers then investigated intermediate forms of the virus, with one or

the other mutation, to see if the change could occur gradually. They found that

intermediate versions of the virus could not infect human cells, so would die

out before they could be transmitted. The researchers say this means the two

genetic mutations would need to occur simultaneously.