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标题: Rab33B通过调节核心膜协会和核衣壳加工来控制乙型肝炎病毒 [打印本页]

作者: StephenW    时间: 2017-6-23 11:08     标题: Rab33B通过调节核心膜协会和核衣壳加工来控制乙型肝炎病毒

Viruses. 2017 Jun 21;9(6). pii: E157. doi: 10.3390/v9060157.
Rab33B Controls Hepatitis B Virus Assembly by Regulating Core Membrane Association and Nucleocapsid Processing.
Bartusch C1, Döring T2, Prange R3.
Author information

1
    Department of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University Mainz, Augustusplatz, D-55131 Mainz, Germany. [email protected].
2
    Department of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University Mainz, Augustusplatz, D-55131 Mainz, Germany. [email protected].
3
    Department of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University Mainz, Augustusplatz, D-55131 Mainz, Germany. [email protected].

Abstract

Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved. Moreover, we found that HBV replication enhanced Rab33B expression. By analyzing HBV infection cycle steps, we identified a hitherto unknown membrane targeting module in the highly basic C-terminal domain of the NC-forming core protein. Rab33B inactivation reduced core membrane association, suggesting that membrane platforms participate in HBV assembly reactions. Biochemical and immunofluorescence analyses provided further hints that the viral core, rather than the envelope, is the main target for Rab33B intervention. Rab33B-deficiency reduced core protein levels without affecting viral transcription and hampered core/NC sorting to envelope-positive, intracellular compartments. Together, these results indicate that Rab33B is an important player in intracellular HBV trafficking events, guiding core transport to NC assembly sites and/or NC transport to budding sites.
KEYWORDS:

Rab GTPase; Rab33B; core/capsid membrane association; hepatitis B virus; nucleocapsid assembly; virus trafficking

PMID:
    28635671
DOI:
    10.3390/v9060157



作者: StephenW    时间: 2017-6-23 11:08

病毒。 2017年6月21日; 9(6)。 pii:E157。 doi:10.3390 / v9060157。
Rab33B通过调节核心膜协会和核衣壳加工来控制乙型肝炎病毒组装。
Bartusch C1,DöringT2,Prange R3。
作者信息

1
    大学医学微生物与卫生系,约翰内斯·古登堡大学美因茨大学医学中心,Augustusplatz,德国美因茨D-55131。 [email protected]
2
    大学医学微生物与卫生系,约翰内斯·古登堡大学美因茨大学医学中心,Augustusplatz,德国美因茨D-55131。 [email protected]
3
    大学医学微生物与卫生系,约翰内斯·古登堡大学美因茨大学医学中心,Augustusplatz,德国美因茨D-55131。 [email protected]

抽象

许多病毒利用细胞运输机制来组装和释放新的感染性颗粒。使用RNA干扰(RNAi),我们证明了肝癌细胞系中乙型肝炎病毒(HBV)传播所需的高尔基体/自噬体相关Rab33B。虽然Rab33B对HBV亚病毒包膜分子的分泌是不必要的,但是其敲低将病毒产量降低到20%,并抑制核衣壳(NC)形成和/或NC运输。 GDP受限制的Rab33B突变体的过表达表现为赤字Rab33B的作用,表明可能涉及Rab33B特异性效应蛋白。此外,我们发现HBV复制增强了Rab33B的表达。通过分析HBV感染周期步骤,我们确定了一个迄今为止未知的膜靶向模块在NC形成核心蛋白的高碱性C-末端结构域。 Rab33B灭活减少核膜结合,提示膜平台参与HBV组装反应。生物化学和免疫荧光分析进一步提示病毒核心而不是信封是Rab33B干预的主要目标。 Rab33B缺乏会降低核心蛋白水平,而不影响病毒转录,阻碍了核心/ NC分选到包膜阳性细胞内区室。这些结果一起表明,Rab33B是细胞内HBV运输事件的重要参与者,指导核心运输到NC装配点和/或NC运输到发芽的地点。
关键词:

Rab GTPase; Rab33B;核心/衣壳膜协会;乙肝病毒;核衣壳组装病毒贩运

结论:
    28635671
DOI:




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