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Mystery behind flu virus transmission solved

Lakdawala, S.S. et al., Nature 526, 122–125 (01 October 2015) doi:10.1038/nature15379

The epidemiological success of flu viruses relies on successful airborne transmission from person to person. But the viral properties governing the airborne transmission of flu viruses are complex. A new study reveals that the soft palate at the back of the roof of the mouth plays a key role in the flu viruses’ ability to transmit through air. Previous research had shown that airborne transmissibility is dependent on the viral surface hemagluttinin (HA) glycoprotein’s ability to bind to receptors on human respiratory cells. Some viral strains bind better to alfa 2-6 glycan receptors found primarily in humans and other mammals while others are better suited to bind alfa 2-3 glycan receptors found in birds.

In the current study, researchers made 4 mutations in the HA protein of the flu virus which made it better suited to bind the bird receptors than the human receptors. They then used this strain to infect ferrets that are often used as models of human influenza infection. In theory the mutated virus should not have spread but it traveled through the air just as well as the wild type virus strain. Upon sequencing the virus genome, the scientists found that it had undergone a genetic reversion that allowed its HA protein to bind to the bird as well as human receptors. This experiment validated that gain of binding to the human receptor is critical for aerosol transmission. On examining the different parts of the respiratory tract, scientists discovered that viruses that genetically reverted were most abundantly found in the soft palate. The researchers are next trying to figure out how this genetic reversion takes place and why particularly in the soft palate. They hypothesize that the viruses outcompete each other in the soft palate from which they can spread by packaging themselves into mucus droplets produced by cells in the soft palate.

From a pandemic point of view, this study enables the systematic evaluation of highly transmissible viruses. The findings published inNature will enable scientists better understand how the flu virus develops airborne transmissibility while helping monitor strains that acquire the potential to cause Influenza outbreaks.

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