TIMM29与乙型肝炎病毒preS1相互作用以调节HBV生命周期

StephenW

TIMM29 interacts with hepatitis B virus preS1 to modulate the HBV life cycle
Nelly Gakii Muriungi 1, Keiji Ueda 1
Affiliations
Affiliation

    1
    Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.

    PMID: 32970362 DOI: 10.1111/1348-0421.12852

Abstract

Hepatitis B virus (HBV), a major global health problem, can cause chronic hepatitis, liver cirrhosis and hepatocellular carcinomas in chronically infected patients. However, before HBV infection can be adequately controlled, many mysteries about the HBV life cycle must be solved. In this study, we identified TIMM29, an inner mitochondrial membrane protein, as an interaction partner of the preS1 region of the HBV large S protein. The interaction was verified by both an immunoprecipitation with preS1 peptides and a GST-pulldown assay. Immunofluorescence studies also showed colocalization of preS1 and TIMM29. Moreover, we determined that the preS1 bound with amino acids 92-189 of the TIMM29 protein. Infection of HBV in TIMM29-overexpressing NTCP/G2 cells resulted in a significant decrease of HBeAg and both extracellular particle-associated and core particle-associated HBV DNA without affecting cccDNA formation. Comparable results were obtained with TIMM29-overexpressing HB611 cells, which constitutively produce HBV. In contrast, knockout of TIMM29 in NTCP/G2 cells led to higher production of HBV including HBeAg expression, as did knockout of TIMM29 in HB611. Collectively, these results suggested that TIMM29 interacts with the preS1 region of the HBV large S protein and modulates HBV amplification. This article is protected by copyright. All rights reserved.

Keywords: Hepatitis B virus; TIMM29; intrinsic immunity; mitochondria; preS1.

This article is protected by copyright. All rights reserved.

StephenW

TIMM29与乙型肝炎病毒preS1相互作用以调节HBV生命周期
Nelly Gakii Muriungi 1，上田敬司1
隶属关系
联系

    1个
    大阪大学医学研究生院微生物学和免疫学系病毒学教研室，日本大阪吹田市山田冈2-2，日本565-0871。

    PMID：32970362 DOI：10.1111 / 1348-0421.12852

抽象

乙型肝炎病毒（HBV）是一个主要的全球性健康问题，可在慢性感染的患者中引起慢性肝炎，肝硬化和肝细胞癌。但是，在可以充分控制HBV感染之前，必须解决许多有关HBV生命周期的谜团。在这项研究中，我们确定了线粒体内膜蛋白TIMM29为HBV大S蛋白preS1区的相互作用伴侣。通过用preS1肽进行免疫沉淀和GST-pulldown分析验证了相互作用。免疫荧光研究还显示了preS1和TIMM29的共定位。此外，我们确定preS1与TIMM29蛋白的氨基酸92-189结合。在过表达TIMM29的NTCP / G2细胞中感染HBV导致HBeAg和细胞外颗粒相关和核心颗粒相关的HBV DNA显着降低，而不会影响cccDNA的形成。使用过表达TIMM29的HB611细胞（可组成性产生HBV）获得了可比的结果。相反，敲除NTCP / G2细胞中的TIMM29会导致更高的HBV产生，包括HBeAg表达，就像敲除HB611中的TIMM29一样。总体而言，这些结果表明TIMM29与HBV大S蛋白的preS1区域相互作用并调节HBV扩增。本文受版权保护。版权所有。

关键字：乙型肝炎病毒； TIMM29;固有免疫力线粒体preS1。

本文受版权保护。版权所有。