April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Neuroinvasiveness of HSV-1 High and Low Phenotypic Reactivators in Aged Infected Human Knock-in Homozygous ApoE4 Transgenic Mice
Author Affiliations & Notes
  • Christian Clement
    LSUHSC, New Orleans, Louisiana
  • Vaibhav Tiwari
    Osteopathic Medicine, Western University, Pomona, California
  • Alberto Musto
    LSUHSC, New Orleans, Louisiana
  • Walter J. Lukiw
    Neuroscience & Ophthalmology, Lousiana State University Health Science Center, New Orleans, Louisiana
  • Partha S. Bhattacharjee
    Biology, Xavier University of Louisiana, New Orleans, Louisiana
  • Harris E. McFerrin, Jr.
    Biology, Xavier University of Louisiana, New Orleans, Louisiana
  • Hilary W. Thompson
    LSUHSC, New Orleans, Louisiana
  • James M. Hill
    LSUHSC, New Orleans, Louisiana
  • Footnotes
    Commercial Relationships  Christian Clement, None; Vaibhav Tiwari, None; Alberto Musto, None; Walter J. Lukiw, None; Partha S. Bhattacharjee, None; Harris E. McFerrin, Jr., None; Hilary W. Thompson, None; James M. Hill, None
  • Footnotes
    Support  NIH NEI EY06311; unrestricted grant from RPB, Inc., Louisiana Lions Eye Foundation; Lions International; Louisiana Vaccine Center, South Louisiana Institute for Infectious Disease Research
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5797. doi:
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      Christian Clement, Vaibhav Tiwari, Alberto Musto, Walter J. Lukiw, Partha S. Bhattacharjee, Harris E. McFerrin, Jr., Hilary W. Thompson, James M. Hill; Neuroinvasiveness of HSV-1 High and Low Phenotypic Reactivators in Aged Infected Human Knock-in Homozygous ApoE4 Transgenic Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5797.

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

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Purpose: : HSV-1 DNA deposition in neuronal tissues, ocular infectious virus shedding, and corneal damage were evaluated in 16-mo-old human homozygous ApoE (4/4 or 2/2) transgenic C57BL/6 mice infected with 17Syn+ (high) or its LAT-promoter-deletion-recombinant 17ΔPst (low) phenotypic reactivator. We have reported characteristic deposition of viral DNA in brain tissue of 5- to 8-mo-old mice (35th IHW 2010, Salt Lake City UT).

Methods: : Corneas were heavily scarified and inoculated with 104 PFU/eye after each female mouse was immunized intraperitoneally with human serum (0.5 ml). A minimum of 20 transgenic and 10 parent non-transgenic mice were infected with 17Syn+ or 17ΔPst(LAT-). Eyes were swabbed daily beginning 1 day post infection (PI) and continuing for 30 consecutive days and then weekly for 6 mos. PFU in the swabs were determined by standard procedures and HSV-1 DNA copy numbers quantified. Viral DNA in TG and brain regions were quantified.

Results: : Each ApoE (4/4) mouse shed 17Syn+ or 17ΔPst(LAT-) up to 14 days PI and more than once thereafter, and all had visible keratitis. Control ApoE (2/2) shed infrequently for 1 week and there was no detectable virus in the parent C57BL/6. Daily HSV-1 DNA recovery frequency averaged 2x102 (controls, 2x10) for 14 days PI. HSV-1 DNA copy numbers in ApoE (4/4) left brain tissues were significantly increased (hippocampus, 9x10; cortex, 1x102) compared to younger mice which were euthanized 30 days PI.

Conclusions: : Our data suggest a novel neurotropic neuronal-connection-pathway of HSV-1 DNA deposition independent of the phenotypic nature of the virus in the presence of the human ApoE (4/4) genetic background. Keratitis, corneal damage (opacity), and neovascularization in all ApoE (4/4) suggest detrimental effects of spontaneous HSV-1 shedding and possible rendering of the latency silencing to be less effective, increasing neuroinvasiveness, neurovirulence, and ocular damage.

Keywords: herpes simplex virus • cornea: basic science • keratitis 

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