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HCV Induces the Expression of Rubicon and UVRAG to Temporally Regulate the Maturation of Autophagosomes and Viral Replication


HCV induces autophagy to benefit its replication. In this report, we demonstrated that HCV infection could induce the expression of both Rubicon and UVRAG, which inhibited and stimulated the maturation of autophagosomes, respectively. The induction of Rubicon by HCV was prompt whereas the induction of UVRAG was delayed, resulting in the accumulation of autophagosomes in the early time points of viral infection. Rubicon positively regulated HCV replication, apparently by increasing the pool of autophagosomes, which could serve as the sites for HCV RNA replication. On the contrary, UVRAG, which reduced the pool of autophagosomes, inhibited HCV replication if it was over-expressed prior to HCV infection. The analysis of HCV genes indicated that the HCV NS4B protein was sufficient to induce the expression of Rubicon and the accumulation of autophagosomes. Our results thus revealed a novel mechanism used by a virus to temporally regulate the autophagic flux for its replication.


Vyšlo v časopise: HCV Induces the Expression of Rubicon and UVRAG to Temporally Regulate the Maturation of Autophagosomes and Viral Replication. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004764
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004764

Souhrn

HCV induces autophagy to benefit its replication. In this report, we demonstrated that HCV infection could induce the expression of both Rubicon and UVRAG, which inhibited and stimulated the maturation of autophagosomes, respectively. The induction of Rubicon by HCV was prompt whereas the induction of UVRAG was delayed, resulting in the accumulation of autophagosomes in the early time points of viral infection. Rubicon positively regulated HCV replication, apparently by increasing the pool of autophagosomes, which could serve as the sites for HCV RNA replication. On the contrary, UVRAG, which reduced the pool of autophagosomes, inhibited HCV replication if it was over-expressed prior to HCV infection. The analysis of HCV genes indicated that the HCV NS4B protein was sufficient to induce the expression of Rubicon and the accumulation of autophagosomes. Our results thus revealed a novel mechanism used by a virus to temporally regulate the autophagic flux for its replication.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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