One Flu Over

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A means of controlling the avian flu pandemic may be in sight. P. Hari reports .

The 1918 Spanish Flu epidemic was one of the biggest global disasters in recent human history. The world was struggling to end the First World War. That was when some people in the Kansas and New York regions began to fall sick with what seemed like a common cold. But the disease was far from being the simple cold, and even farther from being common. Within two years, roughly 62 million people across the globe had died, and this could very well be an underestimate. The virus was highly contagious, and the fatality rate 2.5 per cent. About seven million people died in India.

Thinking about this pandemic still sends a chill up the spines of virologists and epidemiologists. Which is why, after nine decades, it is still a hot topic for research.

Over the years, many potential candidates have appeared on the scene: the Ebola virus, the Marburg Virus and even the HIV or Human Immunodeficiency Virus. However, many biologists think that the most dangerous virus is none of these. It is the avian flu virus.

The avian flu virus is not all that contagious now. It is rare, if at all, to see the infection spread from a human being to another; it spreads only from birds to humans under close proximity. But the fatality rate of this viral infection is over 60 per cent. If a virus with a fatality rate of 2.5 per cent can kill 60 million people, what would happen if the avian flu starts spreading from people to people? How do we know that the virus cannot mutate and get that ability?

Scientists at the Massachusetts Institute of Technology (MIT) in the US have now come up with a partial answer to this question, and it raises hopes of controlling the pandemic, if it happens to arise. They have found the mechanism by which the avian flu virus infects human beings. In the process, they also found that it infects people through a specially shaped receptor in their respiratory tract, a shape that is different in birds. This is probably why the spread of infection from birds to humans has been limited so far. “This discovery can help in designing strategies against a pandemic and may also be important in understanding other influenza viruses,” says Ram Sasisekharan, professor of biological engineering at MIT.

Sasisekharan works in the area of glycobiology, the science of studying sugars. Of late, this field has been rapidly gaining importance, as techniques for studying them keep improving. Sugars are critical to many processes in health and disease. They are important to the functioning of many proteins. Sugars play a big role in the spread of cancers. They are important in bird flu as well.

Significantly, Ram Sasisekharan is the son of Viswanathan Sasisekharan, who was a close associate of the legendary Indian scientist G.N. Ramachandran, who discovered the triple helical structure of collagen, the main protein found in bones, teeth, cartilage and ligaments.

The key to the infection of the flu virus in birds is the binding of a protein found on the surface of the virus called hemagglutinin to the host sugar receptor. There are two kinds of receptors involved in birds and humans. Bird receptors are called alpha 2-3 glycans. The ones in human beings are called alpha 2-6 glycans. The bird flu virus can infect human beings only if its glycoproteins can bind to alpha 2-6 glycans. It is believed that the virus can acquire this ability through mutations. But the MIT team showed that this explanation was simplistic.

(Top) Ram Sasisekharan; and the H5N1 virus (above). The virus does not normally affect humans because of the shape of the receptor

.There are many strains of flu viruses, and only a few can infect humans. Two strains, H1 and H3, have recently acquired the ability to infect humans. The strain that infects birds is called H5, and it sometimes infects humans too, after long and close contact with birds. When it does so, the effect can often be fatal. There have been several isolated cases of outbreaks of H5 infection. But the fact is that they have remained isolated, and have not spread to the larger population.

The new finding by the MIT team, published in this week’s Nature Biotechnology, is that the virus does not bind to all 2-6 glycans in humans. This fact was noticed by scientists earlier, but there had been no satisfactory explanation. The key to binding, showed Sasisekharan and his colleagues, is the shape of the receptor. Birds have cone-shaped receptors, while human beings generally have umbrella-shaped receptors.

Some humans, however, have cone-shaped receptors and it is to these individuals that the virus binds. And this explains why the avian flu does not spread so rapidly.

“Identifying the structure of the receptor to which the viral protein can bind makes this work significant,” says Shahid Jameel, a virologist at the International Centre for Genetic Engineering and Biotechnology, New Delhi. This can help scientists ascertain whether the virus develops pandemic potential through mutations, he says.

This knowledge is valuable in developing vaccines against the avian flu virus. The virus can, however, mutate and develop the ability to bind to umbrella-shaped receptors too. But the MIT team’s work will, hopefully, pave the way to developing strategies to stop the virus in its tracks if that happens.

Sources: The Telegraph (Kolkata, India)

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