Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID) have discovered why some influenza viruses are uncommonly deadly.
In a paper published in the Aug. 18 issue of the Proceedings of the National Academy of Sciences USA, they describe an unusual molecular mechanism that amplifies the disease-causing power of influenza A virus. This mechanism could be a new marker for scientists to examine when attempting to predict the potential for a newly emergent influenza A virus to cause a pandemic. Though still to be proved, their discovery may explain the longtime mystery of how the virus that caused the 1918 influenza pandemic caused more than 20 million deaths worldwide.
"Their findings point us in a direction to better understand the pathology of these more virulent influenza viruses," notes Dominick Iacuzio, Ph.D., program officer for influenza and related viral respiratory diseases at NIAID.
Influenza A viruses possess two surface proteins, hemagglutinin (HA) and neuraminidase (NA). To become infectious, the HA molecule must first be cut into two subunits that help the virus attach to human cells. Normally, influenza viruses remain confined to the respiratory tract because the protease enzymes that cleave HA are common in the lungs and trachea but not in other tissues.
Yoshihiro Kawaoka, D.V.M., Ph.D., and Hideo Goto, D.V.M., Ph.D., of the University of Wisconsin School of Veterinary Medicine in Madison, have discovered that this human influenza A virus is more virulent because it employs a more ubiquitous enzyme, plasmin, to help chop HA in two.
The scientists studied a virus descended from the strain that caused the 1918 pandemic and adapted to grow in mice. Through their experiments, they found that its NA molecule has two distinct structural features that enable it to bind and trap plasminogen, a precursor to plasmin, and thereby accelerate HA cleavage and promote widespread infection of cells.'"/>