Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis
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- Melanie A. Samuel
- Departments of *Molecular Microbiology,
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- Hong Wang
- The Institute for Antiviral Research, Utah State University, Logan, UT 84322
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- Venkatraman Siddharthan
- The Institute for Antiviral Research, Utah State University, Logan, UT 84322
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- John D. Morrey
- The Institute for Antiviral Research, Utah State University, Logan, UT 84322
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- Michael S. Diamond
- Departments of *Molecular Microbiology,
書誌事項
- 公開日
- 2007-10-23
- DOI
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- 10.1073/pnas.0705837104
- 公開者
- Proceedings of the National Academy of Sciences
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説明
<jats:p> West Nile virus (WNV) has emerged as a significant cause of epidemic viral encephalitis and flaccid limb paralysis, yet the mechanism by which it enters the CNS remains uncertain. We used compartmentalized neuron cultures to demonstrate that WNV spreads in both retrograde and anterograde directions via axonal transport. Transneuronal spread of WNV required axonal release of viral particles and was blocked by addition of a therapeutic neutralizing antibody. To test the physiologic significance of axonal transport <jats:italic>in vivo</jats:italic> , we directly inoculated the sciatic nerve of hamsters with WNV. Intrasciatic infection resulted in paralysis of the hind limb ipsilateral but not contralateral to the injection site. Limb paralysis was blocked either by surgical transection of the sciatic nerve or treatment with the therapeutic neutralizing antibody. Collectively, these studies establish that WNV undergoes bidirectional spread in neurons and that axonal transport promotes viral entry into the CNS and acute limb paralysis. Moreover, antibody therapeutics directly inhibit transneuronal spread of WNV infection and prevent the development of paralysis <jats:italic>in vivo</jats:italic> . </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 104 (43), 17140-17145, 2007-10-23
Proceedings of the National Academy of Sciences