Study: Flu virus develops inside mouth's soft tissue before spreading through the air

A new study reveals that the soft palate, the fleshy tissue at the back of the roof of the mouth, is the starting point where an influenza virus develops before traveling through the air. Researchers from Massachusetts Institute of Technology (MIT) and the National Institute of Allergy and Infectious Diseases (NIAID) discovered this while examining the H1N1 flu strain, which caused a 2009 outbreak that killed more than 250,000 people.

The study, which appeared in the online edition of Nature, describes that the soft palate, which separates the back of the mouth with the nasal cavity, plays a key role in viruses' ability to spread from one person to another. When the soft palate becomes infected, it becomes inflamed that leads to coughing and sneezing, the team explains. The findings, the researchers say, should lead to better understanding of the flu virus' airborne transmissibility and help scientists monitor the emergence of strains with the potential to cause a global pandemic.

A virus' airborne transmissibility depends on whether its hemagglutinin, or HA protein can bind to a specific type of receptor on the surface of human respiratory cells, according to MIT biological engineer Ram Sasisekharan, one of the study's senior authors. He says some flu viruses "bind better to alpha 2-6 glycan receptors, found mostly in humans and other mammals, while other viruses are better adapted to alpha 2-3 glycan receptors, found primarily in birds." The study's focus, the 2009 H1N1 flu strain, was discovered to bind to human alpha 2-6 receptors. The team made four mutations in the HA molecule of this virus, making it better suited to bind alpha 2-3 receptors instead of alpha 2-6. They used used these mutations to infect ferrets, which are often used to model human influenza infection.

The researchers found that the mutated virus traveled through the air just as well as its original version. After sequencing the virus' genetic material, they observed that it had undergone a genetic reversion that allowed its HA protein to bind to alpha 2-6 glycan receptors as well as alpha 2-3 glycan receptors. "This is an experimental validation that gain of binding to the 2-6 glycan receptor is critical for aerosol transmission," says Sasisekharan.

To find out the virus' starting point, the team analysed tissue from different parts of the respiratory tract and found that viruses with the genetic reversion were most abundant in the soft palate. After three days of initial infection, 90 percent of the viruses in this region had the reverted form of the virus, while other sites in the respiratory tract had a mix of the two types of virus. The researchers are now trying to study how this reversion occurs, and why it happens in the soft palate. They believe that flu viruses with superior ability to transmit through the air surpass other viruses in the soft palate, from which they can spread by making themselves into mucus droplets. Mucus is produced by goblet cells, found in the soft palate.

After confirming that viruses with the ability to bind to both alpha 2-6 and alpha 2-3 glycan receptors can spread effectively among mammals, this information can now help identify viruses that may cause an epidemic, Sasisekharan says.

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