Jones Scott A, Hu Jianming
Department of Microbiology and Immunology, The Penn State University College of Medicine, Hershey , PA 17033, USA.
Emerg Microbes Infect. 2013 Sep;2(9):e56. doi: 10.1038/emi.2013.56. Epub 2013 Sep 4.
Hepatitis B virus (HBV) infection remains a global health problem with over 350 million chronically infected, causing an increased risk of cirrhosis and hepatocellular carcinoma. Current antiviral chemotherapy for HBV infection include five nucleos(t)ide analog reverse transcriptase inhibitors (NRTIs) that all target one enzymatic activity, DNA strand elongation, of the HBV polymerase (HP), a specialized reverse transcriptase (RT). NRTIs are not curative and long-term treatment is associated with toxicity and the emergence of drug resistant viral mutations, which can also result in vaccine escape. Recent studies on the multiple functions of HP have provided important mechanistic insights into its diverse roles during different stages of viral replication, including interactions with viral pregenomic RNA, RNA packaging into nucleocapsids, protein priming, minus- and plus-strand viral DNA synthesis, RNase H-mediated degradation of viral RNA, as well as critical host interactions that regulate the multiple HP functions. These diverse functions provide ample opportunities to develop novel HP-targeted antiviral treatments that should contribute to curing chronic HBV infection.
乙型肝炎病毒（HBV）感染仍然是一个全球性的健康问题，有超过3.5亿人慢性感染，导致肝硬化和肝细胞癌的风险增加。目前用于HBV感染的抗病毒化疗药物包括五种核苷（酸）类似物逆转录酶抑制剂（NRTIs），它们都靶向一种酶活性，即HBV聚合酶（HP）（一种特殊的逆转录酶（RT））的DNA链延伸活性。NRTIs不能治愈疾病，长期治疗会产生毒性，并出现耐药性病毒突变，这也可能导致疫苗逃逸。最近关于HP多种功能的研究为其在病毒复制不同阶段的多种作用提供了重要的机制见解，包括与病毒前基因组RNA的相互作用、RNA包装进核衣壳、蛋白质引发、负链和正链病毒DNA合成、RNase H介导的病毒RNA降解，以及调节HP多种功能的关键宿主相互作用。这些多样的功能为开发新型的靶向HP的抗病毒治疗提供了充足的机会，有望有助于治愈慢性HBV感染。
