RESUMEN
The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene expression. Understanding PRE's structure, function, and mode of action is essential to leverage its potential as a therapeutic target. A wide range of PRE-based reagents and tools have been developed and assessed in preclinical and clinical settings for therapeutic and biotechnology applications. This manuscript aims to provide a systematic review of the characteristics and mechanism of action of PRE, as well as elucidating its current applications in basic and clinical research. Finally, we discuss the promising opportunities that PRE may provide to antiviral development, viral biology, and potentially beyond.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Procesamiento Postranscripcional del ARN , ARN Viral , Animales , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Regulación Viral de la Expresión Génica , Hepatitis B/virología , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , ARN Mensajero/genética , ARN Viral/genética , ARN Viral/metabolismoRESUMEN
Hepatitis B, the leading cause of liver diseases worldwide, is a result of infection with hepatitis B virus (HBV). Due to its obligate intracellular life cycle, culture systems for efficient HBV replication are vital. Although basic and translational research on HBV has been performed for many years, conventional hepatocellular culture systems are not optimal. These studies have greatly benefited from recent improvements in cell culture models based on stem cell technology for HBV replication and infection studies. Here we describe a protocol for the differentiation of human stem cell-derived hepatocyte-like cells (HLCs) and subsequent HBV infection. HLCs are capable of expressing hepatocyte markers and host factors important for hepatic function maintenance. These cells fully support HBV infection and virus-host interactions. Stem cell-derived HLCs provide a new tool for antiviral drug screening and development.