Studies reveal methods viruses use to sidestep immune system ( ade by the gene is essential to turning...)

Studies reveal methods viruses use to sidestep immune system

ade by the gene is essential to turning on signals that tell the cell to mount an immune response. Cells with the mutated RIG-I protein were unable to initiate immune signals, abolishing the host cells' defenses to HCV.

When HCV infects a cell, the RIG-I protein physically binds the virus genetic material. RIG-I then changes its shape, which sends a cascade of signals to other proteins to activate a transcription factor called interferon regulatory factor 3 (IRF-3). This protein turns on the genes responsible for producing interferon, which neutralizes viruses by suppressing their replication.

The researchers also investigated why cells with functioning RIG-I protein still had persistent HCV infection. In a study to appear in PNAS, Dr. Gale and his group found an explanation for HCV's tenaciousness. Once HCV infects the cell, it launches a counterattack against RIG-I, producing a protein called a protease to disrupt the cell's immune response that is otherwise turned on through RIG-I by the virus infection. The viral protease, NS3/4A, chops up essential signaling proteins involved in carrying RIG-I's message to IRF-3. Without those signals, IRF-3 can't turn on the genes to make interferon, and the virus continues to replicate unimpeded.

"Having identified RIG-I, now we can spend our time completely defining the signaling pathway that goes from RIG-I all the way down to IRF-3," Dr. Gale said. "Once we've done that, we hope to identify parts of the pathway to target with drugs to try to limit infection."

Drugs called protease inhibitors currently are used to treat patients infected with HIV and have also shown promise in treating hepatitis C patients in experimental trials.

"We now know that treating patients with a protease inhibitor will prevent the viral protease from cutting up the signaling proteins," Dr. Gale said. "We're currently working to identify exactly what proteins the viral protease is attacking, which could help
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Source:UT Southwestern

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( ade by the gene is essential to turning...)Studies reveal methods viruses use to sidestep immune system