June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Delivery of Herpes Simplex Virus DNA to Retinal Ganglion Cell Axon is Dependent on Viral Protein Us9
Author Affiliations & Notes
  • Jennifer LaVail
    Dept of Anatomy/Ophthalmology, University of California, San Francisco, San Francisco, CA
  • Jolene Draper
    Dept of Anatomy/Ophthalmology, University of California, San Francisco, San Francisco, CA
  • Graham Stephenson
    Dept of Anatomy/Ophthalmology, University of California, San Francisco, San Francisco, CA
  • Guiqing Huang
    Dept of Anatomy/Ophthalmology, University of California, San Francisco, San Francisco, CA
  • Andrea Bertke
    Proctor Foundation, University of California, San Francisco, San Francisco, CA
  • Daniel Cortez
    Dept of Anatomy/Ophthalmology, University of California, San Francisco, San Francisco, CA
  • Footnotes
    Commercial Relationships Jennifer LaVail, None; Jolene Draper, None; Graham Stephenson, None; Guiqing Huang, None; Andrea Bertke, None; Daniel Cortez, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1730. doi:
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    • Get Citation

      Jennifer LaVail, Jolene Draper, Graham Stephenson, Guiqing Huang, Andrea Bertke, Daniel Cortez; Delivery of Herpes Simplex Virus DNA to Retinal Ganglion Cell Axon is Dependent on Viral Protein Us9. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1730.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The pathogenic spread of neurotropic virus relies on axonal transport of viral DNA. The role of the Herpes Simplex Virus (HSV) protein Us9 in viral intracellular spread is contentious. We compared the results of Us9 deletions in two HSV strains using a novel quantitative assay to test the hypothesis that Us9 regulates the delivery of viral DNA to the distal axon of retinal ganglion cells in vivo. We also deleted a nine amino acid motif in the Us9 protein of F strain (Us9-30) to define the role of this domain in DNA delivery.

Methods: The vitreous chambers of murine eyes were infected with equivalent amounts of F or NS strains of HSV. At three, four or five days post infection (dpi) both optic tracts (OT) were dissected and viral genome was quantified by qPCR.

Results: At three dpi the F strain Us9- and Us9-30 mutants delivered less than 10% and 1%, respectively, of the viral DNA delivered after infection with the Us9R (control) strain. The effect of the deletion of Us9 was less severe in the NS Us9 deletion experiments. By four and five dpi delivery of viral DNA had partially recovered, although to a greater degree in NS as compared to F experiments.

Conclusions: A highly conserved acidic cluster within the Us9 protein plays a critical role for genome transport to the distal axon. The transport is less dependent on Us9 expression in the NS than in F strain virus suggesting compensatory roles for the NS variant. This assay can be used to compare transport efficiency in other neurotropic viral strains.

Keywords: 545 herpes simplex virus • 628 optic flow • 660 proteins encoded by disease genes  
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