Researchers report the biological effects of influenza protein NS1 binding to RIG-I — the binding directly quiets the alarm that activates the cellular innate immunity defense against the infection. This is a newly described way for flu to antagonize the host cellular antiviral response.

Chad Petit, Ph.D., and colleagues at the University of Alabama at Birmingham fight influenza at the molecular level, in part by finding natural mutations in the viral RNA genome that have a functional impact during infection. Discovering how the virus uses these unknown mechanisms to stop your body from mounting an effective defense against infection, Petit said, «will better prepare us to predict the pandemic potential of influenza A virus and aid in the development of vaccines and antivirals.»

Influenza A is dangerous because each year it adapts to various hosts and undergoes genetic reassortment. This generates a constant stream of unique strains that have unknown degrees of pathogenicity, transmissibility and ability to cause international pandemics.

Petit’s latest research, published in the Journal of Biological Chemistry, takes a detailed look at a naturally occurring mutation in a flu strain from a 1972 Russian outbreak that the UAB team described in 2015, while comparing that Russian strain to the 1918 strain responsible for Spanish flu.

The mutation is in the flu protein NS1. In 2015, Petit and his UAB colleagues were the first to show that NS1 from the 1918 strain had a direct interaction with RIG-I, the cell’s main sensor to detect flu virus infection and to then launch an innate immune defense. Furthermore, the portion of the 1918 NS1 RNA binding domain that bound to RIG-I had no previously known function. In contrast to the 1918 NS1, Petit’s lab found that the NS1 from the influenza A strain 1972 Udorn was unable to bind to the RIG-I site that interacted with the 1918 NS1.

Now, Petit and colleagues report the biological effects of NS1 binding to RIG-I — the binding directly quiets the alarm that activates the cellular innate immunity defense against the infection. This is a newly described way to antagonize the host cellular antiviral response.

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Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.