The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation

Abstract

The cis-acting replication element (CRE) of the hepatitis C virus (HCV) RNA genome is a region of conserved sequence and structure at the 3′ end of the open reading frame. It participates in a complex and dynamic RNA-RNA interaction network involving, among others, essential functional domains of the 3′ untranslated region and the internal ribosome entry site located at the 5′ terminus of the viral genome. A proper balance between all these contacts is critical for the control of viral replication and translation, and is likely dependent on host factors. Proteomic analyses identified a collection of proteins from a hepatoma cell line as CRE-interacting candidates. A large fraction of these were RNA-binding proteins sharing highly conserved RNA recognition motifs. The vast majority of these proteins were validated by bioinformatics tools that consider RNA-protein secondary structure. Further characterization of representative proteins indicated that hnRNPA1 and HMGB1 exerted negative effects on viral replication in a subgenomic HCV replication system. Furthermore DDX5 and PARP1 knockdown reduced the HCV IRES activity, suggesting an involvement of these proteins in HCV translation. The identification of all these host factors provides new clues regarding the function of the CRE during viral cycle progression.

N6 -Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection

“…We hypothesize that the non-overlapping YTHDF binding sites in HCV RNA represent m 6 A sites not detected by MeRIP-seq due to biological variation, technical noise, or potentially sites that might be bound by YTHDF proteins in an m 6 A-independent fashion. Indeed, a recent report found that YTHDF proteins bound to an in vitro transcribed, hence non-methylated, HCV RNA genome (Rios-Marco et al, 2016). Therefore, future studies could very well reveal functions of the YTHDF proteins that are independent of m 6 A during the HCV life cycle.…”

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

“…In fact, miR-200 regulates neuronal differentiation in the developing olfactory bulb, an effect that is mediated by inhibition of the zinc finger protein Zeb2 (Beclin et al, 2016). Previous research has shown that miR-200c expression is increased in the adult rodent spinal cord following injury (Yu et al, 2014), in the adult cerebral cortex following ischemic preconditioning (Lee et al, 2010), and following cerebrovascular stroke (Stary et al, 2015).…”

A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8

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