New Discovery Blocks the Replication of Influenza Virus in Cells

A new way to thwart one strain of influenza or flu virus from accessing a human protein it needs to replicate in cells has been discovered by researchers.

The discovery could lead to highly effective ways to treat the flu and could also apply to other respiratory viruses, such as SARS-CoV-2, which causes Covid-19.

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‘SUMOylation inhibitor could lead to highly effective ways to treat the flu and other respiratory viruses’

While the flu is miserable but not life-threatening for many, it kills tens of thousands of people each year, often the youngest and oldest members of a population.

Influenza Virus: New Insights

The Centers for Disease Control and Prevention estimates that flu causes 12,000 to 50,000 deaths in the U.S. each year. 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 but are 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.

To make a person sick, the influenza virus has to infect cells in the body, where it replicates and infects more cells. Jiayu Liao, an associate professor of bioengineering at UC Riverside, previously discovered that the two most common flu viruses, Influenza A and Influenza B, require a unique human protein to proliferate in then infect more cells.

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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.

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Liao’s experiments found that a SUMOylation inhibitor called STE025 can completely block Influenza B virus replication. The work was done with doctoral student Runrui Dang; Victor Rodgers, also a UCR professor of bioengineering; and Adolfo García-Sastre at the Icahn School of Medicine at Mount Sinai.

Influenza B virus treated with the SUMOyaltion inhibitor showed a lack of SUMOylation on the M1 protein and could not replicate in human cells. Influenza A also has SUMOylated proteins and could be susceptible to the SUMOyaltion inhibitor.

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Though more work is needed to understand 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 flu flee forever.

Source-Eurekalert