Medhat Arvin, Arzumanyan Alla, Feitelson Mark A
Department of Molecular Cell Biology, Azad University, North Unit, Tehran, Iran.
Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
Oncotarget. 2021 Nov 23;12(24):2421-2433. doi: 10.18632/oncotarget.28077.
Hepatitis B virus (HBV) is a human pathogen that has infected an estimated two billion people worldwide. Despite the availability of highly efficacious vaccines, universal screening of the blood supply for virus, and potent direct acting anti-viral drugs, there are more than 250 million carriers of HBV who are at risk for the sequential development of hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). More than 800,000 deaths per year are attributed to chronic hepatitis B. Many different therapeutic approaches have been developed to block virus replication, and although effective, none are curative. These treatments have little or no impact upon the portions of integrated HBV DNA, which often encode the virus regulatory protein, HBx. Although given little attention, HBx is an important therapeutic target because it contributes importantly to (a) HBV replication, (b) in protecting infected cells from immune mediated destruction during chronic infection, and (c) in the development of HCC. Thus, the development of therapies targeting HBx, combined with other established therapies, will provide a functional cure that will target virus replication and further reduce or eliminate both the morbidity and mortality associated with chronic liver disease and HCC. Simultaneous targeting of all these characteristics underscores the importance of developing therapies against HBx.
乙型肝炎病毒（HBV）是一种人类病原体，全球估计有20亿人受到感染。尽管有高效疫苗可用，对血液供应进行病毒普遍筛查，还有强效的直接作用抗病毒药物，但仍有超过2.5亿HBV携带者面临着依次发展为肝炎、纤维化、肝硬化和肝细胞癌（HCC）的风险。每年有超过80万人死于慢性乙型肝炎。人们已经开发出许多不同的治疗方法来阻断病毒复制，尽管这些方法有效，但没有一种是能治愈的。这些治疗方法对整合型HBV DNA的部分几乎没有影响，而整合型HBV DNA通常编码病毒调节蛋白HBx。尽管很少受到关注，但HBx是一个重要的治疗靶点，因为它在以下方面发挥重要作用：（a）HBV复制；（b）在慢性感染期间保护受感染细胞免受免疫介导的破坏；（c）在HCC的发展过程中。因此，开发针对HBx的疗法，并与其他已有的疗法相结合，将提供一种功能性治愈方法，既能靶向病毒复制，又能进一步降低或消除与慢性肝病和HCC相关的发病率和死亡率。同时针对所有这些特性凸显了开发针对HBx疗法的重要性。
