乙型肝炎病毒（HBV）的sK122R突变与隐匿性HBV感染有关：对一

StephenW

The sK122R mutation of hepatitis B virus (HBV) is associated with occult HBV infection: Analysis of a large cohort of Chinese patients
Jun Wang  1 , Yan Liu  2 , Hao Liao  2 , Lujie Liu  2 , Rongjuan Chen  2 , Lanlan Si  2 , Dan Luo  2 , Bixia Huang  2 , Le Li  2 , Jiandong Jiang  3 , Dongping Xu  4
Affiliations
Affiliations

    1
    Peking University 302 Clinical Medical School, Beijing 100039, China; Institute of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
    2
    Institute of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
    3
    The Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: [email protected].
    4
    Peking University 302 Clinical Medical School, Beijing 100039, China; Institute of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China. Electronic address: [email protected].

    PMID: 32763811 DOI: 10.1016/j.jcv.2020.104564

Abstract

Background: Occult HBV infection (OBI) is of great concern due to their complicated diagnosis and potential for public transmission.

Objective: The study aimed to determine the clinical prevalence of OBI and if viral immune escape-associated mutations contribute to the occurrence of OBI.

Study design: A total of 91,037 HBV-infected patients with different related illnesses who were admitted to the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2017 were tested for OBI. Serum samples from 62 patients with OBI manifestations (OBI patients) and 124 matched non-OBI patients were sequenced for possible immune escape-associated mutations within the major hydrophilic region of HBV S protein. HBsAg and HBV DNA levels in representative viral strains were measured.

Results: Of the 91,037 tested patients, 487 (0.53 %) were negative for HBsAg but positive for HBV DNA and were defined as OBI patients. The prevalence in different illness categories varied. Immune escape-associated mutations were more frequently detected in OBI patients than in non-OBI patients (59.68 % vs. 35.48 %, P < 0.01), as did the coexistence of multiple mutations (43.55 % vs. 22.58 %, P < 0.01). Specifically, the prevalence rates of sT118 K, sK122R, and sV168A were increased in OBI patients. Strains with sK122R mutants (sK122R, sK122R + D144E, sK122R + C121R + D144E, and sK122R + F134L + D144E) from a follow-up OBI patient all showed significantly lower levels of HBsAg production than a wild-type strain.

Conclusions: The study clarified the clinical prevalence of OBI, verified the influence of immune escape-associated mutations, and identified the role of the sK122R mutation in multiple OBI patients.

Keywords: HBsAg; Hepatitis B virus; Immune escape-associated mutation; Major hydrophilic region; Occult HBV infection.

Copyright © 2020. Published by Elsevier B.V.

StephenW

乙型肝炎病毒（HBV）的sK122R突变与隐匿性HBV感染有关：对一大批中国患者的分析
王军1，柳柳2，郝辽2，刘路杰2，陈荣娟2，兰兰寺2，丹罗2，碧霞黄2，乐丽2，姜建东3，徐东平4
隶属关系
隶属关系

    1个
    北京大学302临床医学院，北京100039；中国人民解放军总医院第五医学中心传染病研究所，北京100039
    2
    中国人民解放军总医院第五医学中心传染病研究所，北京100039
    3
    中国医学科学院药物生物技术研究所，北京100050电子地址：[email protected]。
    4
    北京大学302临床医学院，北京100039；中国人民解放军总医院第五医学中心传染病研究所，北京100039电子地址：[email protected]。

    PMID：32763811 DOI：10.1016 / j.jcv.2020.104564

抽象

背景：隐匿性HBV感染（OBI）由于其复杂的诊断和潜在的公共传播潜力而备受关注。

目的：该研究旨在确定OBI的临床患病率以及病毒免疫逃逸相关突变是否有助于OBI的发生。

研究设计：2005年1月至2017年12月在中国人民解放军总医院第五医疗中心收治的91,037例不同相关疾病的HBV感染患者进行了OBI测试。对来自62例具有OBI表现的患者（OBI患者）和124例匹配的非OBI患者的血清样本进行了测序，以检测HBV S蛋白主要亲水区内可能发生的与免疫逃逸相关的突变。测量了代表性病毒株中的HBsAg和HBV DNA水平。

结果：在91,037名接受测试的患者中，有487名（0.53％）HBsAg阴性但HBV DNA阳性，被定义为OBI患者。不同疾病类别的患病率各不相同。与非OBI患者相比，OBI患者中免疫逃逸相关突变的检出率更高（59.68％vs. 35.48％，P <0.01），多种突变的共存（43.55％vs. 22.58％，P <0.01） 。具体而言，OBI患者中sT118 K，sK122R和sV168A的患病率增加。来自随访OBI患者的带有sK122R突变体（sK122R，sK122R + D144E，sK122R + C121R + D144E和sK122R + F134L + D144E）的菌株均显示出比野生型菌株明显更低的HBsAg产生水平。

结论：该研究阐明了OBI的临床患病率，验证了免疫逃逸相关突变的影响，并确定了sK122R突变在多个OBI患者中的作用。

关键字：HBsAg；乙型肝炎病毒;免疫逃逸相关突变；主要亲水区；隐匿性HBV感染。

版权所有©2020。由Elsevier B.V.发布。