Antibody microarray for signalome-wide assessment of host cell response to hepatitis C virus

Antibody microarray for signalome-wide assessment of host cell response to hepatitis C virus

Hepatitis C Virus (HCV) affects about two per cent of the world's population. Infection can lead to chronic hepatitis, which can progress to liver cirrhosis and carcinoma.

An international study has shone light on the way the HCV hijacks the communication systems in the host cells it infects, uncovering potential new therapeutic targets for the disease.

Importantly, the approach used by the scientists - which led to the identification of a drug-like molecule that stopped the virus from replicating within cells - may have broader application to other infectious diseases. This is because all intracellular pathogens rely on their host cell signalling system to replicate.

The study, published in Nature Communications, focused on protein kinases, enzymes that are key regulators of cellular processes. It built on previous ground-breaking work on malaria published in 2011 that found that if host cell protein kinases were prevented from working it would kill malaria parasites.

The researchers used an antibody microarray to simultaneously investigate hundreds of factors involved in cell signalling that were modulated by HCV replication, including human protein kinases.

"This antibody microarray allowed us to find a number of new cell signalling pathways that were activated or suppressed by an HCV infection," senior author said.

The researchers then used gene silencing technology to determine whether the genes' cell factors identified using the antibody microarray were indeed important for HCV replication and therefore potential targets for anti-HCV compounds.

They were then able to use a compound recently discovered to block the activity of one of the kinases important in HCV replication, MAP4K2.

"The platform we have established can be adopted to identify new anti-infective compounds against any pathogen including, viruses, bacteria and parasites, that invade mammalian cells," senior author 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," senior author said.

The researchers will now extend their work in studies on the Zika virus and toxoplasmosis.

https://www.monash.edu/news/articles/study-points-to-new-approach-to-battling-infections

https://www.nature.com/articles/ncomms15158

Edited

Rating

Unrated