New Clues in HCV Replication

Scientists have identified several new host factors which provide clues about how the cis-acting replication element (CRE) functions in the hepatitis C virus (HCV). The research, conducted by Pablo Rios-Marco of the Institute of Parasitology and Biomedicine in Granada, Spain, and colleagues, and was published in Nature in May, 2016.

“The present work provides evidence that the CRE associates with a collection of cellular proteins, most of them reported here for the first time, which allows them to connect with the HCV genome,”the authors wrote.

In fact, they identified 55 host proteins that, they say, “are pulled-down by an RNA transcript corresponding to the HCV CRE,” many of which are being identified as HCV-interacting for the first time.

Most of the proteins identified in this study were nucleic acid binding proteins, which, say the researchers, “suggests direct association between them and the CRE.” They add that protein-mediated interactions cannot be ruled out.

Two proteins related to regulating translation were also identified, leading the researchers to say, “[this] suggests an association between the translational machinery and the CRE when the cellular scenario is suitable.”

Additionally, the researchers selected some proteins to investigate whether or not they were involved in HCV replication. They found that one in particular, hnRNPA1, “clearly downregulates HCV replication,” they report, adding “due to the limitation of the replicon system, we cannot exclude the possibility of a partial effect of hnRNPA1 knockdown on HCV replication by direct interaction with NS5B or even synergic effects of both actions.”

The researchers conclude that more work will be required in order to fully interpret their results and gain an understanding of how these proteins function in the viral cycle.