与隐匿基因型乙型肝炎病毒感染相关的新型乙型肝炎病毒表

StephenW

J Viral Hepat. 2020 Apr 26. doi: 10.1111/jvh.13309. [Epub ahead of print]
Novel hepatitis B virus surface antigen mutations associated with occult genotype Bhepatitis B virus infection affect HBsAgdetection.
Wang H1,2, Wang M2, Huang J2, Xu R2, Liao Q2, Shan Z2, Zheng Y2, Rong X2, Tang X1, Li T1, Wang W1, Li C1, Fu Y1,2.
Author information

1
    Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
2
    Guangzhou Blood Center, Guangzhou, China.

Abstract

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV were investigated. Fifty-seven HBsAg positive/HBV DNA positive blood donors served as control group for comparison. Occult HBV related mutations with a high incidence (P<0.05) in the S gene were identified. To further verify theseoccult infection related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg were analyzed by Electrochemical luminescence and Cellular Immunohistochemistry. Ten occult infection related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P<0.05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P<0.05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P<0.05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P<0.0001). Hence ten mutations were associated with genotype B occult HBV - E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.

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KEYWORDS:

Hepatitis B virus; HepatitisB surface antigen; Mutation; occult hepatitis B Infection

PMID:
    32336003
DOI:
    10.1111/jvh.13309

StephenW

J病毒性肝炎。 2020年4月26日。doi：10.1111 / jvh.13309。 [Epub提前发行]
与隐匿基因型乙型肝炎病毒感染相关的新型乙型肝炎病毒表面抗原突变会影响HBsAg检测。
Wang H1,2，Wang M2，Huang J2，Xu R2，Liao Q2，Shan Z2，Zheng Y2，Rong X2，Tang X1，Li T1，Wang W1，​​Li C1，Fu Y1,2。
作者信息

1个
    南方医科大学检验医学与生物技术学院输血医学系，广州
2
    中国广州市广州血液中心。

抽象

隐匿性乙型肝炎感染的病因很复杂，尚未完全阐明。乙型肝炎病毒（HBV）S基因突变是可能导致隐性感染的因素之一。在这项研究中，调查了89位B型隐匿性HBV献血者。 57个HBsAg阳性/ HBV DNA阳性献血者作为对照组进行比较。在S基因中发现了隐匿性HBV相关突变，其发生率很高（P <0.05）。为了进一步验证这些隐匿感染相关的突变，构建了HBV B基因型的保守全基因表达载体（pHBV1.3B）。然后，构建基于pHBV1.3B的突变质粒并将其转染到HepG2细胞中。通过电化学发光和细胞免疫组织化学分析细胞外和细胞内HBsAg。在隐匿性感染组中，十个隐性感染相关突变（E2G，Q101R，K122R，M133T，D144E，G145R，V168A，S174N，L175S和I226S）显着更频繁（P <0.05）。十个突变中的五个（E2G，D144E，G145R，V168A和S174N）在转染系统中强烈降低了细胞外HBsAg水平（P <0.05）。值得注意的是，E2G突变对细胞外HBsAg（3.8％vs pHBV1.3B）和细胞内HBsAg的比例（239.3％vs pHBV1.3B）的影响最大（P <0.05），E2G突变HBsAg的荧光密度为明显高于pHBV1.3B（P <0.0001）。因此，与基因型B隐匿的HBV相关的有10个突变-E2G和V168A是新颖的突变，我们证实了它们显着影响HBsAg检测。 E2G可能会引起HBsAg分泌障碍，从而导致细胞内积聚和HBsAg分泌减少。

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关键字：

乙型肝炎病毒;乙型肝炎表面抗原；突变;隐匿性乙型肝炎感染

PMID：
    32336003
DOI：
    10.1111 / jvh.13309