Abstract
Hepatitis C virus (HCV) is a small positive-sense single-stranded RNA virus that causes severe liver diseases. Current anti-HCV therapies involving direct-acting antivirals have significantly enhanced efficacy in comparison to traditional interferon and ribavirin combination. However, further improvement is needed to eradicate HCV. Anacardic acid (AnA) is a phytochemical compound that can inhibit the activity of various cellular enzymes including histone acetyltransferases (HATs). In this study, we investigated the effects of AnA on different phases of HCV life cycle. Our data showed that AnA can inhibit HCV entry, replication, translation, and virion secretion in a dose-dependent manner with no measurable effects on cell viability. In addition, we showed that two HAT inhibitors and knocking down HAT (PCAF) by RNAi can reduce HCV replication, suggesting a mechanism of AnA’s inhibitory effects on HCV. Elucidation of the AnA-mediated inhibitory mechanism should facilitate the development of new drug candidates for HCV infection.
Highlights
Hepatitis C virus (HCV), a member of the genus Hepacivirus within the virus family Flaviviridae, is able to establish chronic infection in humans, eventually leading to liver cirrhosis, hepatocellular carcinoma and liver failure [1,2]
Given the multiple activities of Anacardic acid (AnA) identified previously, we investigated whether AnA could modulate distinct components of the HCV life cycle
HCV-2a J6/JFH-1 genomic replicon cells were treated with different concentrations of AnA for 48 or 72 h and expression of viral protein (NS5A) levels were determined by Western blotting
Summary
Hepatitis C virus (HCV), a member of the genus Hepacivirus within the virus family Flaviviridae, is able to establish chronic infection in humans, eventually leading to liver cirrhosis, hepatocellular carcinoma and liver failure [1,2]. More than 170 million people worldwide are infected with HCV, 80–85% of which are chronic infections. Dependent on HCV genotype, this treatment is successful in 45–80% of cases. It is very costly and often associated with strong side effects [4,5]. A few direct-acting antiviral (DAA) drugs targeting HCV nonstructural proteins have been licensed with improved efficacy. These DAAs have limitations, such as drug resistance, heavy pill load, high cost, and PLOS ONE | DOI:10.1371/journal.pone.0117514. These DAAs have limitations, such as drug resistance, heavy pill load, high cost, and PLOS ONE | DOI:10.1371/journal.pone.0117514 February 6, 2015
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