HBsAg，亚病毒颗粒及其在建立慢性乙型肝炎病毒感染的功能性

StephenW

HBsAg, Subviral Particles, and Their Clearance in Establishing a Functional Cure of Chronic Hepatitis B Virus Infection
Andrew Vaillant  1
Affiliations
Affiliation

    1
    Replicor Inc., 6100 Royalmount Avenue, Montreal, Quebec H8Y 3E6, Canada.

    PMID: 33302622 DOI: 10.1021/acsinfecdis.0c00638

Abstract

In diverse viral infections, the production of excess viral particles containing only viral glycoproteins (subviral particles or SVP) is commonly observed and is a commonly evolved mechanism for immune evasion. In hepatitis B virus (HBV) infection, spherical particles contain the hepatitis B surface antigen, outnumber infectious virus 10 000-100 000 to 1, and have diverse inhibitory effects on the innate and adaptive immune response, playing a major role in the chronic nature of HBV infection. The current goal of therapies in development for HBV infection is a clinical outcome called functional cure, which signals a persistent and effective immune control of the infection. Although removal of spherical SVP (and the HBsAg they carry) is an important milestone in achieving functional cure, this outcome is rarely achieved with current therapies due to distinct mechanisms for assembly, secretion, and persistence of SVP, which are poorly targeted by direct acting antivirals or immunotherapies. In this Review, the current understanding of the distinct mechanisms involved in the production and persistence of spherical SVP in chronic HBV infection and their immunoinhibitory activity will be reviewed as well as current therapies in development with the goal of clearing spherical SVP and achieving functional cure.

Keywords: HBsAg; RNAi; functional cure; immune inhibition; integrated HBV DNA; nucleic acid polymers; quasispecies; subviral particle.

StephenW

HBsAg，亚病毒颗粒及其在建立慢性乙型肝炎病毒感染的功能性治疗中的清除作用
安德鲁·威兰特1
隶属关系
联系

    1个
    Replicor Inc.，加拿大魁北克蒙特利尔H8Y 3E6，Royalmount Avenue 6100。

    PMID：33302622 DOI：10.1021 / acsinfecdis.0c00638

抽象

在各种病毒感染中，通常观察到仅含有病毒糖蛋白（亚病毒颗粒或SVP）的过量病毒颗粒的产生，并且是免疫逃逸的常见进化机制。在乙型肝炎病毒（HBV）感染中，球形颗粒包含乙型肝炎表面抗原，数量超过10000-100 000的传染性病毒，并且对先天和适应性免疫反应具有多种抑制作用，在慢性疾病中起主要作用乙肝病毒感染。 HBV感染发展中的治疗方法的当前目标是称为功能性治愈的临床结果，这表明对感染的持续有效免疫控制。尽管去除球形SVP（及其所携带的HBsAg）是实现功能性治愈的重要里程碑，但由于SVP的组装，分泌和持久性机制不同，而直接作用的靶向性差，因此目前的治疗方法很少能达到这种效果抗病毒药或免疫疗法。在本综述中，将综述目前对慢性HBV感染中球形SVP的产生和持久性及其免疫抑制活性所涉及的独特机制的理解，以及目前正在开发的旨在清除球形SVP和实现功能性治愈的治疗方法。

关键字：HBsAg； RNAi；功能性治疗免疫抑制整合的HBV DNA；核酸聚合物；准种亚病毒颗粒。