Community Research and Development Information Service - CORDIS

FP7

LIPOHCV Result In Brief

Project ID: 293664
Funded under: FP7-PEOPLE
Country: Spain

A fresh attack on hepatitis C

There are around 150 million cases of hepatitis C virus (HCV) infection globally. Despite the rise in effective antiviral treatments generally, there is still a need for efficient but cost-effective therapies with reduced side-effects.
A fresh attack on hepatitis C
The LIPOHCV (Hepatitis C virus and host lipoprotein metabolism) project has focused on a group of genes involved in HCV replication, the lipins. Involved in the regulation of lipids and lipoprotein metabolism in normal cells, research work showed that several of these genes are harnessed by HCV and mediate different aspects of the virus' life cycle.

Infection was reduced when the team interfered experimentally with two lipins suggesting that these could be potential molecular targets for anti-HCV therapy. More interesting still, as some of these genes functionally overlap there is a low likelihood that inactivation will interfere with lipid metabolism. Only attacking viral infection may result in less side-effects.

Viral infection has links with lipid metabolism and causes liver disease. Research results may lead to a greater understanding of how this happens.

Using imaging techniques and international research collaboration, the researchers produced 3D nanoscale maps of the physical changes induced by HCV in the cell. The virus appears to take over the cell mitochondria for viral replication. Moreover, the team discovered a gene, SIGMAR1, involved with both virus replication and cross-talk between cell organelles including the mitochondrion.

The SIGMAR1 protein product interacts with key enzymes in cholesterol biosynthesis and its depletion changes expression of genes involved in lipid and cholesterol metabolism. For the future, the LIPOHCV team intend to extend studies on the proteomic analysis of proteins that interact with SIGMAR1.

The novel factors controlling early HCV infection are candidate molecular targets for host-targeting agents. Besides complementing the new anti-HCV therapies based on direct-acting antivirals, these agents could raise the genetic barrier to resistance and cover a wide range of virus genotypes. They also put future research on the path to unscrambling the molecular details of host-virus interactions, another source of novel therapies.

Related information

Keywords

Hepatitis C, HCV, lipoprotein metabolism, lipin, host-targeting agents
Record Number: 183173 / Last updated on: 2016-08-16
Domain: Biology, Medicine