May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Viral Regulation of the Long Distance Axonal Transport of Herpes Simplex Virus Nucleocapsid in vivo
Author Affiliations & Notes
  • J. H. LaVail
    Anatomy, University of California, San Francisco, San Francisco, California
  • A. N. Tauscher
    Anatomy, University of California, San Francisco, San Francisco, California
  • O. Harrabi
    Anatomy, University of California, San Francisco, San Francisco, California
  • A. Sucher
    Anatomy, University of California, San Francisco, San Francisco, California
  • Footnotes
    Commercial Relationships  J.H. LaVail, None; A.N. Tauscher, None; O. Harrabi, None; A. Sucher, None.
  • Footnotes
    Support  NIH EY08773 and That Man May See, Inc.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 494. doi:https://doi.org/
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      J. H. LaVail, A. N. Tauscher, O. Harrabi, A. Sucher; Viral Regulation of the Long Distance Axonal Transport of Herpes Simplex Virus Nucleocapsid in vivo . Invest. Ophthalmol. Vis. Sci. 2008;49(13):494. doi: https://doi.org/.

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

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Abstract

Purpose: : Herpes simplex virus (HSV) infections are responsible for recurrent corneal herpetic keratitis, as well as sporatic acute encephalitis. Even with antiviral treatment, the incidence of mortality or of severe neurological deficits after HSV encephalitis remains high. Our long-term goal is to identify the viral and infected host proteins that promote the spread of HSV into the central nervous system. In previous work we have found that newly synthesized HSV is axonally transported in at least two sub-assemblies, one of which is the viral nucleocapsid and DNA. We have also found that the protein Us9 is essential for the anterograde transport of the nucleocapsid. We have begun to look at the role of other viral proteins in regulating the anterograde transport of nucleocapsid.

Methods: : We used an in vivo mouse retinal ganglion cell model and infected the retinas with mutant and wild-type viral strains of HSV.

Results: : In immuno-precipitation assays we identified at least five viral proteins that associate with Us9 in infected retinal ganglion cell axons. When we probed the western blots of immuno-precipitation eluate with an antibody to VP22, we confirmed a band that was VP22. We also tested the function of VP22 in axonal transport by using a HSV mutant strain that lacked the gene UL49 that expresses VP22 (and consequently failed to express the tegument protein VP22). This VP22-null strain transported less than 5% of the viral DNA in the optic pathway of infected mice, as compared to the transport by control, repaired VP22 strain.

Conclusions: : Two viral proteins, Us9 and VP22, facilitate efficient axonal transport of viral capsid and DNA. Based on additional evidence that VP22 is also associated with the kinesin heavy chain, we now propose a working model in which Us9 modulates the interaction of VP22 with both the kinesin heavy chain motor complex and the major protein of the viral capsid.

Keywords: herpes simplex virus • keratitis • antiviral drugs 
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