# Poly(rC)-Binding Protein 2 Does Not Directly Participate in HCV Translation or Replication, but Rather Modulates Genome Packaging

## TL;DR

This study shows that PCBP2 does not directly help HCV replicate or translate, but instead affects how the virus packages its genome into new virus particles.

## Contribution

The novel finding is that PCBP2 modulates HCV genome packaging rather than directly participating in translation or replication.

## Key findings

- PCBP2 does not directly affect HCV entry, translation, genome stability, or RNA replication.
- PCBP2 depletion impacts viral RNAs that can undergo genome packaging.
- PCBP2 modulates early steps of genome packaging, indirectly affecting translation and replication.

## Abstract

The hepatitis C virus (HCV) co-opts many cellular factors—including proteins and microRNAs—to complete its life cycle. A cellular RNA-binding protein, poly(rC)-binding protein 2 (PCBP2), was previously shown to bind to the hepatitis C virus (HCV) genome; however, its precise role in the viral life cycle remained unclear. Herein, using the HCV cell culture (HCVcc) system and assays that isolate each step of the viral life cycle, we found that PCBP2 does not have a direct role in viral entry, translation, genome stability, or HCV RNA replication. Rather, our data suggest that PCBP2 depletion only impacts viral RNAs that can undergo genome packaging. Taken together, our data suggest that endogenous PCBP2 modulates the early steps of genome packaging, and therefore only has an indirect effect on viral translation and RNA replication, likely by increasing the translating/replicating pool of viral RNAs to the detriment of virion assembly.