Researchers studied how the virus hijacks infected cells.
A new study shows how the hepatitis C virus (HCV) hijacks the communication systems of the cells it infects, helping researchers identify a drug-like molecule that stopped HCV from replicating in
The investigation, led by Monash University’s Biomedicine Discovery Institute in Clayton, Australia, may help uncover potentially new therapeutic targets for the liver-attacking virus.
The approach also may have broader applications for other infectious diseases. That’s because all intracellular pathogens rely on their host cell signaling system to replicate, researchers said.
“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,” Christian Doerig (pictured), PhD, a Monash professor who heads the university’s microbiology department, said.
Doerig published research on malaria in 2011 that focused on protein kinases — the enzymes that are key to regulating cellular processes. The team found that if host cell protein kinases were prevented from working, it would kill malaria parasites.
In the HCV study, Doerig again focused on protein kinases. Collaborating with Kinexus Bioinformatics Corp. in Vancouver, Canada, the BDI team used an antibody microarray, which detects interactions between an antibody and its target antigen.
The team simultaneously investigated hundreds of factors involved in cell signaling that were modulated by HCV replication, including human protein kinases.
“This antibody microarray allowed us to find a number of new cell signaling pathways that were activated or suppressed by an HCV infection,” Doerig said.
The researchers then used gene silencing technology to determine whether the genes’ cell factors identified by the antibody microarray were important for HCV replication. This would make them potential targets for anti-HCV compounds, according to the study. The researchers enlisted a newly discovered molecule to block the activity of one of the kinases key to HCV replication — MAP4K2.
When the researchers put the molecule into the host cells and infected them with HCV, they discovered that the cells were fine, but they didn’t support virus replication anymore, Dr. Reza Haqshenas, a microbiology research fellow at Monash and the study’s chief investigator, said.
“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,” Doerig said.
Hepatitis C affects about 2% of the world's population and can progress to liver cirrhosis, cancer, and death. The researchers plan to extend their work in studies on the Zika virus and toxoplasmosis.
The paper, titled “Signalome-wide assessment of host cell response to Hepatitis C virus,” was published in Nature Communications on May 8.
A press release regarding the study was made available.