亚病毒乙型肝炎病毒长丝被释放等经由多泡体的感染性病毒

StephenW

J Virol. 2015 Dec 30. pii: JVI.03109-15. [Epub ahead of print]
Subviral hepatitis B virus filaments are released like infectious viral particles via multivesicular bodies.Jiang B1, Himmelsbach K1, Ren H1, Boller K2, Hildt E3.
Author information

• 1Paul-Ehrlich-Institut, Department of Virology; Langen, Germany.
• 2Paul-Ehrlich-Institut, Department of Immunology.
• 3Paul-Ehrlich-Institut, Department of Virology; Langen, Germany DZIF- German Center of Infection Research Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich-Str. 51-55, D-63325 Langen, Germany. [email protected].
  

AbstractIn addition to infectious viral particles, hepatitis B virus-replicating cells secrete high amounts of subviral particles assembled by the surface proteins, but lacking any capsid and genome. Subviral particles form spheres (22 nm particles) and filaments. Filaments contain a much higher amount of the large surface protein (LHBs) as compared to spheres. Spheres are released via the constitutive secretory pathway, while viral particles are ESCRT-dependently released via multivesicular bodies (MVBs). The interaction of virions with the ESCRT machinery is mediated by α-taxilin that connects the viral surface protein LHBs with the ESCRT-component tsg101. Since filaments in contrast to spheres contain a significant amount of LHBs, it is unclear whether filaments are released like spheres or like virions. To study the release of subviral particles in absence of virion formation, a core-deficient HBV mutant was generated. Confocal microscopy, immune electron microscopy of ultrathin sections and isolation of MVBs revealed that filaments enter MVBs. Inhibition of MVB biogenesis by the small molecule inhibitior U18666A or inhibition of ESCRT-functionality by coexpression of transdominant negative mutants (Vps4A, Vps4B, CHMP3) abolishs the release of filaments while secretion of spheres is not affected. These data indicate that in contrast to spheres which are secreted via the secretory pathway, filaments are released via ESCRT/MVB pathway like infectious viral particles.
IMPORTANCE: The study revises the current model describing the release of subviral particles by showing that in contrast to spheres, which are secreted via the secretory pathway, filaments are released via the ESCRT/MVB pathway like infectious viral particles. These data significantly contribute to a better understanding of the viral morphogenesis and might be helpful for the design of novel antiviral strategies.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

StephenW

病毒学杂志。 2015年30月PII：JVI.03109-15。 [打印EPUB提前]
亚病毒乙型肝炎病毒长丝被释放等经由多泡体的感染性病毒颗粒。
江B1，Himmelsbach K1，任H1，伯乐K2，Hildt E3。
作者信息

    1Paul - 埃利希学院病毒学系;兰根，德国。
    2Paul - 埃利希学院免疫学系。
    3Paul - 埃利希学院病毒学系;兰根，感染研究保罗 - 埃利希学院，病毒学，保罗 - 埃利希-STR系德国DZIF-德国中心。 51-55，D- 63325兰根，德国。 [email protected]。

抽象

除了感染性病毒颗粒，乙型肝炎病毒复制的细胞分泌大量的表面蛋白组装亚病毒颗粒的，但缺少任何衣壳和基因组。亚病毒颗粒形成球体（22纳米粒子）和长丝。花丝包含相比，球高得多的数额大的表面蛋白（LHBs的）的。球体是通过组成型分泌途径释放，而病毒颗粒是ESCRT依赖性经由多泡体（MVBs）释放。病毒粒子与ESCRT机械的相互作用是由α-taxilin连接该病毒表面蛋白质LHBs的与ESCRT组分TSG101介导的。因为在对比球体长丝含有显著量LHBs的的，目前还不清楚是否长丝被释放样球体或类似的病毒粒子。以研究在不存在病毒粒子的形成亚病毒颗粒的释放，产生一个核心缺失的HBV突变体。共聚焦显微镜，超薄切片和MVBs的隔离免疫电镜显示，长丝进入MVBs。 MVB生物发生的由小分子inhibitior U18666A或抑制ESCRT-功能通过transdominant负突变体（VPS4A，Vps4B，CHMP3）共表达抑制abolishs长丝的释放而球体的分泌不受影响。这些数据表明，在对比它们通过分泌途径分泌的球体，细丝通过ESCRT / MVB通路像感染性病毒颗粒释放。
重要性：

该研究修改当前模型通过表明在对比球，它们通过分泌途径分泌，长丝被通过ESCRT / MVB通路像感染性病毒颗粒释放的描述亚病毒颗粒的释放。这些数据显著有助于更好地了解病毒的形态发生和可能是新型抗病毒策略的设计有所帮助。

版权所有©2015年，美国微生物学会。版权所有。

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