A Key to Fighting Severe Viruses

Scientists seem to have figured out a way to attack a protein that many viruses rely on to replicate.

It has been difficult to treat viruses that cause severe disease because there are few options for effective treatment. Many viral infections, such as the common cold, cause mild illnesses that the body’s immune system eventually defeats.

But researchers at Washington University School of Medicine​ in St. Louis have demonstrated a way to dial up the body’s innate immune defenses while simultaneously attacking the deadly protein.

The findings, published in Nature Immunology, reveal previously unknown weapons in the body’s antiviral immune arsenal and provide guidelines for designing drugs that could be effective against a broad range of viruses.

According to a news release from Washington University, the strategy involves enhancing the body’s interferon signaling system, long understood to be a vital part of antiviral defenses.

“We’ve discovered a new component of the interferon system,” said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine. “It does something that other components don’t do, and it works on both sides of the fence: It dials up the body’s internal genes that fight viruses, and it attacks viral proteins directly.”

The investigators used a mouse model to reach their conclusion.

When infected with encephalomyocarditis virus, which causes severe damage to vital organs including the brain, heart and pancreas, 97 percent of mice genetically altered by the researchers survived, compared with none of the control mice. Even when the concentration of the injected virus was increased 100-fold, 82 percent of the genetically altered mice survived. And at 100-fold lower concentrations, all genetically engineered mice survived the infection, compared with only 25-28 percent of the control mice.

Analyzing the mice, the researchers found that the genetic alteration that confers these benefits turns on a set of molecules called PARP9-DTX3L. This molecular complex activates genes specifically designed to fight viruses. And, separate from its role in activating genes, the complex also seeks out and destroys an important viral protein called 3C protease, the scientists found. Many viruses including the common cold virus rely on this protein to replicate and continue their destructive march through the body.

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