A team of UC Riverside bioengineers has just found a way to block one strain of the influenza virus from accessing a human protein it needs to replicate in cells. And this discovery could lead to highly effective ways to treat the flu and could also apply to other respiratory viruses, such as Covid-19.

Each year the flu is miserable for hundreds of millions of people and it kills hundreds of thousands worldwide. Often the youngest and oldest members of a population suffer the most. The Centers for Disease Control and Prevention estimates that, just in the United States, the flu causes 12,000 to 50,000 deaths. 

Flu vaccines, which work by teaching the body’s immune system how to recognize and attack the virus when it enters the body, are not always effective for reasons scientists don’t yet fully understand. This is likely related to the complexities of the immune system and viral mutations.

The new research, published in the journal Viruses, does not rely on the immune system to stop the virus.

In order to make a person sick, the influenza virus has to infect cells in the body, where it replicates and infects more cells. The UC Riverside researchers previously discovered that the two most common types of flu virus, Influenza A and Influenza B, require a unique human protein to proliferate in cells and then infect more cells.

The current work has identified a way to prevent Influenza B virus replication by blocking this necessary protein. Without the protein, virus amplification is blocked completely in cells.

The Influenza B virus uses a human cellular process called SUMOylation to modify a gene called M1, which plays multiple roles in the influenza viral life cycle. SUMOylation occurs when small ubiquitin-like modifier, or SUMO, proteins attach to and detach from other proteins to change their biochemical activities and functions.

The team’s experiments found that a SUMOylation inhibitor called STE025 can completely block Influenza B virus replication.

The Influenza B virus treated with the SUMOyaltion inhibitor showed lack of SUMOylation on the M1 protein and was incapable of replicating in human cells. Influenza A also has SUMOylated proteins and could be susceptible to the SUMOyaltion inhibitor as well.

Though more work is needed for a thorough understanding of Influenza B’s dependence on SUMOylation, the finding that STE025 inhibits SUMOylation and prevents flu virus replication brings science one big step closer to making us flu free forever.

- VIRUSES, January 24, 2022, “Human SUMOylation Pathway Is Critical for Influenza B Virus,” by Runrui Dang, et al. © 2022MDPI (base, Switzerland unless otherwise stated. All rights reserved.