# A cross-talk between Hepatitis B virus and host mRNAs confers viral adaptation to liver

## TL;DR

This study shows how Hepatitis B virus interacts with a liver-specific microRNA to enhance its replication and adapt to the host environment.

## Contribution

The study reveals a novel mechanism where HBV uses miR-122 response elements to manipulate host gene expression and promote viral replication.

## Key findings

- HBV uses miR-122 response elements to increase its expression and replication in liver cells.
- HBV mRNA can down-regulate miR-122 and alter host gene expression, aiding viral replication.
- Mutations in miR-122 response elements correlate with higher viral loads and disease progression in patients.

## Abstract

Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide. The replication of HBV which genome is only 3.2 kb long relies heavily on host factors. Previous studies demonstrated that a highly expressed liver-specific microRNA (miRNA) miR-122 suppresses HBV expression and replication in multiple ways. In this study, we found that the miR-122 response elements in viral genome facilitate HBV expression and replication in miR-122 highly-expressed hepatocytes. Moreover, mutations in miR-122 response elements are correlated with viral loads and disease progression in HBV-infected patients. We next found that HBV mRNA with miR-122 response elements alone could lead to altered expression of multiple host genes by whole genome expression analysis. HBV mRNA-mediated miR-122 down-regulation plays a major role in HBV mRNA-induced differential gene expression. HBV mRNA could enhance viral replication via miR-122 degradation and the up-regulation of its target cyclin G1. Our study thereby reveals that under the unique condition of high abundance of miR-122 and viral mRNAs and much lower level of miR-122 target in HBV infection, HBV may have evolved to employ the miRNA-mediated virus and host mRNAs network for optimal fitness within hepatocytes.