GENETIC ANALYSIS OF HERPES VIRUS NEUROTROPISM AND ENCEPHALITIS

疱疹病毒向神经性和脑炎的遗传分析

基本信息

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A critical step in the transmission of Herpes simplex virus type 1 virus (HSV) from one infected neuron to the next is the polarized anterograde axonal transport of viral DNA from the host infected nerve cell body to the axon terminal for subsequent release. How the virus is transported and what viral proteins are necessary are long-standing questions. Using an HSV mutant virus that lacks expression of the Us9 protein and the infected murine retinal ganglion cell model, we found that HSV Us9 protein is necessary specifically for long distance anterograde axonal transport of viral capsid and DNA. It is unnecessary for anterograde transport of viral envelope proteins or for retrograde axonal transport of HSV. Using an immunoaffinity matrix of Us9 antibody coupled to Sepharose beads, we co-concentrated Us9 and VP5, the major capsid protein. This biochemical evidence suggests a mechanism by which the capsid transport depends on an association with Us9 protein. This association was further confirmed with EM immunohistochemistry in which Us9 antibody labeled unenveloped capsids in wild-type virus infected retinal ganglion cell cytoplasm. We conclude that efficient axonal transport of HSV DNA and capsid depends on expression of Us9 protein and does not require the traditional membrane vesicle proteins that are associated with many host cell motors. We shall affinity purify proteins that associate with Us9 on the affinity matrix and then separate them on PAGE. The proteins will be silver stained and cut out of the gels for identification using mass spectroscopy for identification. As a model of non-vesicular transport, the anterograde axonal transport of HSV nucleocapsid offers a new biochemical tool for understanding this functional process in normal neurons. Furthermore, Us9 protein is a potential therapeutic target against the spread of HSV in the visual system.
这个子项目是众多研究子项目之一

项目成果

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JENNIFER Hart LAVAIL其他文献

JENNIFER Hart LAVAIL的其他文献

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{{ truncateString('JENNIFER Hart LAVAIL', 18)}}的其他基金

Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    7849349
  • 财政年份:
    2009
  • 资助金额:
    $ 0.18万
  • 项目类别:
Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    8134126
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    8129516
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
LONG DISTANCE AXONAL TRANSPORT OF HSV CAPSID AND DNA
HSV 衣壳和 DNA 的长距离轴突运输
  • 批准号:
    7724217
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    7678405
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    7911698
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
Genetic analysis of Herpes virus neurotropism and encephalitis
疱疹病毒嗜神经性和脑炎的遗传分析
  • 批准号:
    7515042
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
LONG DISTANCE AXONAL TRANSPORT OF HSV CAPSID AND DNA
HSV 衣壳和 DNA 的长距离轴突运输
  • 批准号:
    7601862
  • 财政年份:
    2007
  • 资助金额:
    $ 0.18万
  • 项目类别:
HSV and Host Cell Contributions to Corneal Infection
HSV 和宿主细胞对角膜感染的影响
  • 批准号:
    6422401
  • 财政年份:
    2002
  • 资助金额:
    $ 0.18万
  • 项目类别:
HSV and Host Cell Contributions to Corneal Infection
HSV 和宿主细胞对角膜感染的影响
  • 批准号:
    6744750
  • 财政年份:
    2002
  • 资助金额:
    $ 0.18万
  • 项目类别:

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