The Interactions between HBV and the Innate Immunity of Hepatocytes.

Fayed Attia Koutb Megahed,Xiaoling Zhou,Pingnan Sun

doi:10.3390/v12030285

Abstract

Hepatitis B virus (HBV) infection affects ~350 million people and poses a major public health problem worldwide. HBV is a major cause of cirrhosis and hepatocellular carcinoma. Fewer than 5% of HBV-infected adults (but up to 90% of HBV-infected infants and children) develop chronic HBV infection as indicated by continued, detectable expression of hepatitis B surface antigen (HBsAg) for at least 6 months after the initial infection. Increasing evidence indicates that HBV interacts with innate immunity signaling pathways of hepatocytes to suppress innate immunity. However, it is still not clear how HBV avoids monitoring by the innate immunity of hepatocytes and whether the innate immunity of hepatocytes can be effective against HBV if re-triggered. Moreover, a deep understanding of virus–host interactions is important in developing new therapeutic strategies for the treatment of HBV infection. In this review, we summarize the current knowledge regarding how HBV represses innate immune recognition, as well as recent progress with respect to in vitro models for studying HBV infection and innate immunity.

Highlights

Chronic infection with hepatitis B virus (HBV) is the main cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide
One study demonstrated the inhibition of signal transducer and activator of transcription 1 (STAT1) nuclear import by HBV polymerase, and showed that hepatitis B surface antigen (HBsAg) and/or Hepatitis B Virus X Protein (HBx) protein interfered with the STAT1 signaling [39]
All these findings provide evidence that HBV can counteract the innate immune responses mediated by TLRs or RIG-I in the liver microenvironment, which might be strategies by which HBV escapes the surveillance of the host innate immune system

Summary

Introduction

Chronic infection with hepatitis B virus (HBV) is the main cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. We summarize the recent knowledge and debate regarding HBV and innate immunity signaling pathways in hepatocytes, the different HBV proteins that target innate immunity, and different advanced in vitro cell models for the study of virus–host interactions Collation of such information will provide new insights into novel therapeutic treatments for chronic hepatitis B infection (CHB). It has a relaxed partially double-stranded circular DNA genome of about 3200 bases with four main overlapping open reading frames (ORFs) encoding surface protein (pre-S/S), pre-core/core (pre-C/C), transcriptional co-activator (X), and DNA polymerase (P) genes [11]. Pregenomic RNA (pgRNA) is packaged by core protein, along with the polymerase protein, and the viral genome is replicated through reverse transcription (RT) of the pgRNA to form the - strand, followed by partial synthesis of the + strand (Steps 8 and 9). Mature nucleocapsids can either be recycled back to the nucleus to maintain a pool of cccDNA, or enveloped and secreted through the endosomal sorting complexes required for transport (ESCRT) pathway (Steps 10, 11 and 12)

HBV Infection and Host Innate Immunity

Conflicts Regarding HBV and Innate Immunity

In Vitro Models to Study HBV Infection and Innate Immunity

Findings

Conclusions