Sunday 23 November, 2014

Mutation that could allow H1N1 to spread much more easily identified

Published On: Thu, Mar 10th, 2011 | Flu | By BioNews

In a new study from MIT, researchers have identified a single mutation in the H1N1 genetic makeup that would allow it to be much more easily transmitted between people.

The finding should give the World Health Organization, which tracks influenza evolution, something to watch out for, said Ram Sasisekharan, senior author of the paper.

“There is a constant need to monitor the evolution of these viruses,” said Sasisekharan, the Edward Hood Taplin Professor and director of the Harvard-MIT Division of Health Sciences and Technology. Some new H1N1 strains have already emerged, and the key question, Sasisekharan adds, is whether those strains will have greater ability to infect humans.

WHO labs around the world are collecting samples of human and avian flu strains, whose DNA is sequenced and analyzed for potential significant mutations. However, it’s difficult, with current technology, to predict how a particular DNA sequence change will alter the structure of influenza proteins, including hemagglutinin (HA), which binds to receptors displayed by cells in the human respiratory tract. Now that this specific HA mutation has been identified as a potentially dangerous one, the WHO should be able to immediately flag any viruses with that mutation, if they appear.

Identifying this mutation is an important step because it is usually very difficult to identify which of the many possible mutations of the HA protein will have any impact on human health, says Qinghua Wang, assistant professor of biochemistry at Baylor College of Medicine.

“These are exactly the types of mutations that we need to watch out for in order to safeguard humans from future disastrous flu pandemics,” he said.

In the new study, the MIT researchers focused on a segment of the HA protein that they have shown affects its ability to bind to respiratory cells. They created a virus with a single mutation in that region, which replaced the amino acid isoleucine with another amino acid, lysine. That switch greatly increased the HA protein’s binding strength. They also found that the new virus spread more rapidly in ferrets, which are commonly used to model human influenza infection.

If such a mutant virus evolved, it could generate a “second wave” like the ones seen in 1918 and in 1957 (known as the “Asian flu”).

“If you look at the history, it takes a very small change to these viruses to have a dramatic effect,” Sasisekharan said.

The amino acid in question is located in a part of the viral genome prone to mutate frequently, because it is near the so-called antigenic site — the part of the HA protein that interacts with human antibodies. Antigenic sites tend to evolve rapidly to escape such antibodies, which is why flu vaccine makers have to use new formulas every year. This year’s vaccine included a strain of H1N1, which is still circulating around the world.

The study has been published in the journal Public Library of Science (PLoS) One. (ANI)

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