Researchers Identify and Block Cell Signaling Pathways Used by Hepatitis C Virus

Researchers Identify and Block Cell Signaling Pathways Used by Hepatitis C Virus

Scientists at the Monash University’ Biomedicine Discovery Institute have provided new insights into the cell signaling pathways used by the hepatitis C virus (HCV), and how the virus is able to hijack patients’ communication systems. The new research opens up new avenues for scientists to explore to develop new treatments.

Host cell signaling following infection with parasites and other intracellular pathogens is not well understood. However, if cell signaling pathways can be identified and selectively blocked, it opens up many new possibilities for treating a wide range of viral, bacterial and parasitic diseases.

The researchers used an antibody microarray to analyze hundreds of cell signaling factors simultaneously. The team found several new signaling pathways that were either activated or suppressed because of an infection with HCV, including human protein kinases.

The researchers identified new cell signaling pathways and then determine whether they were important for HCV replication by using gene silencing techniques. The study builds on previous work by Professor Christian Doerig on malaria.

Previous studies have shown that interfering with protein kinase activity kills malaria parasites. The new study showed that a compound capable of silencing gene activity and blocking the activity of the protein kinase MAP4K2, a kinase important for HCV replication, stopped the virus from replicating.

The use of the antibody microarray in combination with gene silencing techniques allowed the researchers to study several factors involved in viral replication. The researchers said, “The combination of antibody microarray and gene silencing represents a novel, system-wide approach for the understanding of infectious disease biology.”

Christian Doerig, who was a co-author of the paper, said the use of antibody microarrays and gene silencing can “provide a strong basis for the development of urgently needed lead compounds against not only viruses but also any intracellular pathogens of bacterial or protist taxons.”

Doerig said, “Importantly, fighting a pathogen by hitting an enzyme from the host cell is likely to slow the emergence of drug resistance, because the pathogen cannot easily escape through the selection of target mutations,”

The researchers are now planning to use the technique to study the Zika virus and Toxoplasma gondii.

The study – Signalome-wide assessment of host cell response to hepatitis C virus –  was recently published in Nature Communications.

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