Research Discovery May Explain Why Interferon-Induced Therapies Fail for Hepatitis C Patients

Research Discovery May Explain Why Interferon-Induced Therapies Fail for Hepatitis C Patients

Researchers at the University of Washington have discovered that the virus that causes hepatitis C is capable of manipulating infected liver cells from the host, blocking signaling pathways that can trigger an antiviral response by the immune system. This finding may explain why interferon-induced drug therapies are ineffective for many patients.

The study, “Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling,” was published in the journal Nature Medicine.

Hepatitis C virus is the most common cause of chronic hepatitis and the leading cause of liver cancer in the U.S. This team of researchers now has discovered a new mechanism by which the virus manipulates the host cells to protect itself from the attack of the immune system.

Upon infection with the virus, the host liver cells secrete proteins called interferons. There are several types of interferon proteins, but they all work by inducing the expression of several genes that, once activated, promote virus-fighting proteins within the cell. The action of interferons is so important that one of them, called interferon-alpha, has been used for years, either alone or combined with the antiviral drug ribavirin, as a powerful therapy against chronic hepatitis C virus infections. While this therapy has helped many patients, it still fails in about 60% of the infected individuals.

Despite the fact new, more efficient therapies have been introduced, the reason interferon-based therapy fails in such a high proportion of patients has remained poorly understood.

In this study, the research team hypothesized that the virus somehow was manipulating the cell response. The same team of researchers previously found that infected cells activate two genes, the MYH7 and MYH7B, which then produced molecules that can interfere with the production of other proteins, called microRNAs. Researchers went on to show that these microRNAs interfered with the production of interferons induced by hepatitis C virus. Hence, this was a mechanism triggered by the virus to prevent cells’ to fully mount a response against the virus.

Researchers now believe the microRNAs induced by hepatitis C virus infection also are inhibiting a receptor that is key for the cells’ antiviral response via interferons.

The results show that the hepatitis C virus modulates cell-induced interferon’s response at multiple levels, to assure a successful infection.

“The finding helps explain why many patients fail certain drug treatments, and should help develop more effective alternate treatment protocols,” said the study’s lead author, Ram Savan, PhD, in a press release.  Savan is an assistant professor of immunology in the University of Washington School of Medicine.

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