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bioRxiv · 10.1101/2022.04.12.488029

The cellular poly(rC)-binding protein 2 prevents the early steps of hepatitis C virus virion assembly

Cousineau, S. E.·Sagan, S. M.
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Abstract

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, we found that PCBP2 does not directly affect viral entry, translation, genome stability, replication, or virion egress. Rather, our data suggests that endogenous PCBP2 normally limits virion assembly, thereby indirectly promoting translation and replication by increasing the translating/replicating pool of viral RNAs. Additionally, we found that an alternative RNA conformation (SLIIalt) was important for efficient virion assembly, but functions in a PCBP2-independent manner. The latter may explain why the Japanese fulminant hepatitis 1 isolate is able to produce infectious particles in cell culture, while other HCV isolates are lost in translation. Taken together, our results suggest that PCBP2 and SLIIalt independently modulate HCV genome packaging and alter the balance of viral RNAs in the translating/replicating pool and those engaged in virion assembly. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

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Cousineau, S. E., Sagan, S. M.. 2022-04-12. The cellular poly(rC)-binding protein 2 prevents the early steps of hepatitis C virus virion assembly. https://doi.org/10.1101/2022.04.12.488029

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