The requirement for at least two simultaneous genetic mutations to occur before avian strains of flu readily transmit between people could explain why viruses such as H5N1 haven’t yet caused a human pandemic, according to research by scientists in the U.K. and U.S.

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Results from the study, by researchers at Imperial College London, the University of Reading, and the UniversityNorth Carolina, have also provided new insights into viral transmission that could help the development of a vaccine for the future.

Using in vitro models of human airway epithelia and tissue sections, the researchers studied a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread.

They first found that while H5 viruses can currently only infect ciliated cells in the upper airways, in order to transmit between humans, avian strains would also need to be able to infect nonciliated cells as well.

By manipulating the viral genes, they then demonstrated that two genetic changes would need to occur in the HA gene simultaneously before the virus could infect cells necessary for transmission between humans. The research is published in PLoS ONE in a paper titled, “Mutations in H5N1 Influenza Virus Hemagglutinin That Confer Binding To Human Tracheal Airway Epithelium.”

H5N1 has infected about 400 people since 2003, and has a high mortality rate in humans, at around 60%, the scientists point out. “H5N1 is a particularly nasty virus so when humans started to get infected with bird flu, people started to panic,” explains Imperial College’s professor Wendy Barclay, corresponding author on the PLoS ONE paper. “Thankfully we haven’t 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.

“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,” she continues. “The odds of it undergoing the kind of double mutation that would be needed are extremely low.”

Nevertheless, the researchers stress, complacency should be avoided. “Our new findings do not mean that this kind of pandemic could never happen,” Professor Barclay continues. “It’s important that scientists keep working on vaccines so that people can be protected if such an event occurs.”

Source: GEN News

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Public-health officials are breathing a small sigh of relief that the H1N1 swine flu virus hasn’t mutated to become more deadly since emerging last spring. But what are the chances it will?

To find out, scientists at the CDC recently launched experiments in the agency’s labs in which they infected ferrets with both the new H1N1 virus and the highly lethal H5N1 avian flu virus to see if they might “reassort” to create a new hybrid.

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The scientists want to know whether a combination of the H1N1 virus -– highly transmissible, but not terribly deadly -– and the H5N1 flu virus could create an easily transmissible, deadly scourge. The H5N1 virus has only sickened 440 people world-wide since 2003 and generally isn’t transmitted from one person to another. But it has killed 262, or about 60%, of those people, according to the World Health Organization.

As the new H1N1 flu has spread, flu experts have kept a close eye on Egypt and parts of the world where human H5N1 infections are occurring too. The two viruses could mix if they infected the same person simultaneously. The new H1N1 virus was also detected recently in turkeys in Chile, proving that it has the capacity to jump to birds, another potential source for reassortment.

The CDC scientists don’t have results of their lab experiments in ferrets yet, said Michael Shaw, associate director for laboratory science for the agency’s influenza division. While the experiments could produce viable combinations of the two viruses, the real question is whether any could create a virus that would spread, he said. “Viability is one thing,” he cautioned. “Whether it’s easily transmissible is another.”

Other experiments conducted so far suggest the new H1N1 virus isn’t terribly prone to doomsday changes. Viruses can change through either mutation of genetic material, or by reassorting with another flu virus. The new virus is lacking certain characteristics that would allow it to mutate to become more virulent, said Nancy Cox, chief of the CDC’s influenza division. “It would be difficult for this virus to acquire some of those known virulence markers,” she said.

As for reassortment, so far the new H1N1 virus hasn’t shown a penchant for mixing with other common flu viruses. In a research note published in late August on the Web site PloS Currents: Influenza, scientists infected ferrets both with the new H1N1 virus and common seasonal strains of H1N1 and H3N2 flu. The new H1N1 pandemic virus didn’t reassort.

“Co-infection of seasonal and pandemic strains did not result in the rapid selection of reassortant viruses that either improved replication or transmission or exacerbated virulence,” they concluded. The federally funded study was led by scientists at the University of Maryland.

Whatever any of the experiments show, CDC officials warn against drawing definitive conclusions. “Influenza is really unpredictable,” Cox said.

Source: The Wall Street Journal

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