期刊
VIRUSES-BASEL
卷 15, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/v15040981
关键词
hepatitis C virus; NS5A; cyclophilin A; cyclosporin; host-targeting agents
类别
Direct-acting antivirals (DAAs) provide interferon-free strategies for hepatitis C treatment, while host-targeting agents (HTAs) exhibit high resistance and distinct mechanisms of action. Our research shows that cyclosporin A (CsA), a HTA targeting cyclophilin A, can suppress HCV infection as quickly as DAAs, but has a different effect on intracellular virus replication.
Several direct-acting antivirals (DAAs) are available, providing interferon-free strategies for a hepatitis C cure. In contrast to DAAs, host-targeting agents (HTAs) interfere with host cellular factors that are essential in the viral replication cycle; as host genes, they are less likely to rapidly mutate under drug pressure, thus potentially exhibiting a high barrier to resistance, in addition to distinct mechanisms of action. We compared the effects of cyclosporin A (CsA), a HTA that targets cyclophilin A (CypA), to DAAs, including inhibitors of nonstructural protein 5A (NS5A), NS3/4A, and NS5B, in Huh7.5.1 cells. Our data show that CsA suppressed HCV infection as rapidly as the fastest-acting DAAs. CsA and inhibitors of NS5A and NS3/4A, but not of NS5B, suppressed the production and release of infectious HCV particles. Intriguingly, while CsA rapidly suppressed infectious extracellular virus levels, it had no significant effect on the intracellular infectious virus, suggesting that, unlike the DAAs tested here, it may block a post-assembly step in the viral replication cycle. Hence, our findings shed light on the biological processes involved in HCV replication and the role of CypA.
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