Abstract:
:The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for the identification of novel connections and functions of different neural circuitries. However, how H129 viral particles are transported in neurons, especially those of the central nervous system, remains unclear. In this study, we constructed recombinant H129 variants with mCherry-labeled capsids and/or green fluorescent protein (GFP)-labeled envelopes and infected the cortical neurons to study axonal transport of H129 viral particles. We found that different types of viral particles were unevenly distributed in the nucleus, cytoplasm of the cell body, and axon. Most H129 progeny particles were unenveloped capsids and were transported as capsids rather than virions in the axon. Notably, capsids acquired envelopes at axonal varicosities and terminals where the sites forming synapses are connected with other neurons. Moreover, viral capsids moved more frequently in the anterograde direction in axons, with an average velocity of 0.62 ± 0.18 μm/s and maximal velocity of 1.80 ± 0.15 μm/s. We also provided evidence that axonal transport of capsids requires the kinesin-1 molecular motor. These findings support that H129-derived tracers map the neural circuit anterogradely and possibly transsynaptically. These data will guide future modifications and improvements of H129-based anterograde viral tracers.IMPORTANCE Anterograde transneuronal tracers derived from herpes simplex virus 1 (HSV-1) strain 129 (H129) are important tools for mapping neural circuit anatomic and functional connections. It is, therefore, critical to elucidate the transport pattern of H129 within neurons and between neurons. We constructed recombinant H129 variants with genetically encoded fluorescence-labeled capsid protein and/or glycoprotein to visualize viral particle movement in neurons. Both electron microscopy and light microscopy data show that H129 capsids and envelopes move separately, and notably, capsids are enveloped at axonal varicosity and terminals, which are the sites forming synapses to connect with other neurons. Superresolution microscopy-based colocalization analysis and inhibition of H129 particle movement by inhibitors of molecular motors support that kinesin-1 contributes to the anterograde transport of capsids. These results shed light into the mechanisms for anterograde transport of H129-derived tracer in axons and transmission between neurons via synapses, explaining the anterograde labeling of neural circuits by H129-derived tracers.
journal_name
J Viroljournal_title
Journal of virologyauthors
Dong X,Zhou J,Qin HB,Xin B,Huang ZL,Li YY,Xu XM,Zhao F,Zhao CJ,Liu JJ,Luo MH,Zeng WBdoi
10.1128/JVI.01957-19subject
Has Abstractpub_date
2020-03-31 00:00:00issue
8eissn
0022-538Xissn
1098-5514pii
JVI.01957-19journal_volume
94pub_type
杂志文章abstract::Cyclosporine (CsA) and its derivatives potently suppress hepatitis C virus (HCV) replication. Recently, CsA-resistant HCV replicons have been identified in vitro. We examined the dependence of the wild-type and CsA-resistant replicons on various cyclophilins for replication. A strong correlation between CsA resistance...
journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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doi:10.1128/JVI.02680-15
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3448-3454.1992
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pub_type: 杂志文章
doi:10.1128/jvi.74.12.5712-5715.2000
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.5.2916-2927.1992
更新日期:1992-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.8.4746-4751.1995
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pub_type: 杂志文章
doi:10.1128/jvi.77.17.9451-9462.2003
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3506-3508.1988
更新日期:1988-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1887-1894.1995
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pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
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journal_title:Journal of virology
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.11.5.730-735.1973
更新日期:1973-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.12.6469-6479.2004
更新日期:2004-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2004-12-01 00:00:00
abstract::A series of contiguous 30-bp deletions were introduced into the regions upstream of the p19 and p40 promoters of adeno-associated virus (AAV), and the effects of these deletions on induction of AAV transcription by the rep gene products was evaluated. A novel complementation system was devised for supplying wild-type ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.6.2936-2945.1991
更新日期:1991-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.3.847-853.1982
更新日期:1982-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6788-6793.1992
更新日期:1992-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7214-7224.2003
更新日期:2003-07-01 00:00:00