Acid-sensitive molecular changes contribute to the emergence of pandemic influenza

[tetano]

St. Jude Children's Research Hospital scientists have identified a molecular property of the hemagglutinin protein that contributed to the emergence of the 2009 H1N1 pandemic influenza virus. The findings may help officials recognize and control flu viruses that pose the greatest risk to humans. The study appears today in the online, early edition of the scientific journal Proceedings of the National Academy of Sciences (PNAS).


Hemagglutinin is carried on the surface of the flu virus. The virus needs the protein for binding to and infecting host cells.
The researchers showed that hemagglutinin became more stable in an acidic environment as the H1N1 virus shifted from swine to humans. The adaptation increased the protein's stability in the acidic conditions of the human respiratory tract and lowered the pH at which hemagglutinin was activated. Activation triggers an irreversible change in the protein's molecular shape that fuses the virus and target cell.
Investigators demonstrated in the laboratory that the hemagglutinin adaption was essential for airborne viral transmission in ferrets, the animal model of the human disease. Mutating hemagglutinin to reduce the protein's stability in acid, and increase the pH of activation, blocked the virus' ability to spread through airborne particles.


http://medicalxpress.com/news/2016-01-acid-sensitive-molecular-contribute-emergence-pandemic.html

 

[tetano]

The original article

 

[sharon sanders]

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[h=2]Significance[/h] Influenza pandemics occur several times per century, causing millions of deaths. For one of the myriad of zoonotic influenza viruses to do so, a virus containing a hemagglutinin (HA) surface antigen previously unseen by most humans must evolve the necessary, albeit largely unknown, properties for sustained respiratory spread between people. During entry, the prototypic viral fusion protein HA binds receptors and is triggered irreversibly by low pH in endosomes to cause membrane fusion. These studies link a fundamental property, activation energy of a fusion protein measured as its pH of activation (acid stability), to the ability of zoonotic influenza viruses to cause a human pandemic. Monitoring HA stability is expected to enhance prepandemic surveillance and control of emerging influenza viruses.

http://www.pnas.org/content/early/2016/01/20/1524384113.abstract