How HCV promotes replication? Hepatitis C Virus (HCV) is a global health problem necessitating novel measures. European scientists investigated how the virus affects the metabolic state of infected cells to promote replication and survival. Health © Shutterstock Hundreds of millions of people become infected with HCV every year. Because of the lack of a prophylactic vaccine and the limited therapies available, persistent HCV infection can lead to chronic hepatitis, cirrhosis and liver cancer. Accumulating evidence indicates that disease progression involves metabolic alteration of lipid biogenesis and homeostasis in the liver. Scientists on the EU-funded HCVFAO (Hepatitis C virus infection dysregulates mitochondrial fatty acid oxidation) project set out to unravel the association between HCV infection and host mitochondrial lipid beta-oxidation. Beta-oxidation is the process by which our bodies break down lipids to produce energy. Utilising a tissue culture model of HCV infection, HCVFAO discovered that HCV infection attenuated mitochondrial lipid beta-oxidation activity early on during infection to promote viral replication. This alteration resulted in poor lipid combustion and low energy production, triggering a shift of energy expenditure toward glycolysis. Investigation into the underlying mechanism unveiled that HCV infection attenuated mRNA transcription of the mitochondrial trifunctional protein (MTP), a key enzyme in lipid beta-oxidation. The presence of inflammatory cytokines worsened the situation by causing additive gene suppression. Furthermore, the impaired beta-oxidation made cells less responsive to type I interferon-mediated virus suppression. Collectively, HCVFAO results clearly indicate that HCV interference with lipid β-oxidation plays a pivotal role for the establishment of a long-term, persistent infection. Further understanding of this aspect of virus/host interaction may lead to the improvement of existing therapies and the design of novel targeted interventions. Keywords Hepatitis C virus, lipid, beta-oxidation, MTP
