July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A Surprising Failure of Herpes Simplex Virus Type 1 (HSV-1) to Spread to the Brain or Contralateral Retina Following Uniocular Inoculation of Mice with Retrovirus-induced Immunosuppression (MAIDS)
Author Affiliations & Notes
  • Madeline Welch
    Georgia State University, Atlanta, Georgia, United States
  • Jessica Carter
    Georgia State University, Atlanta, Georgia, United States
  • Lauren Duncan
    Georgia State University, Atlanta, Georgia, United States
  • Jay Oh
    Georgia State University, Atlanta, Georgia, United States
  • Richard D Dix
    Georgia State University, Atlanta, Georgia, United States
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Madeline Welch, None; Jessica Carter, None; Lauren Duncan, None; Jay Oh, None; Richard Dix, None
  • Footnotes
    Support  NIH Grant EY010568, NIH Grant EY024630, NIH/NEI Core Grant P30/EY006360, Emory Eye Center Vision Training Grant NIH/NEI T32EY007092, Research to Prevent Blindness, and Fight for Sight
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 516. doi:
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    • Get Citation

      Madeline Welch, Jessica Carter, Lauren Duncan, Jay Oh, Richard D Dix; A Surprising Failure of Herpes Simplex Virus Type 1 (HSV-1) to Spread to the Brain or Contralateral Retina Following Uniocular Inoculation of Mice with Retrovirus-induced Immunosuppression (MAIDS). Invest. Ophthalmol. Vis. Sci. 2018;59(9):516.

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

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Abstract

Purpose : Progressive outer retinal necrosis (PORN), a clinical variant of acute retinal necrosis (ARN), is an uncommon but devastating complication of AIDS that has a herpesvirus etiology. We sought to develop an experimental animal model of HSV-1-induced PORN using C57BL/6 mice with MAIDS to better understand its pathophysiology. Because mice with retrovirus-induced MAIDS suffer from impaired cellular immunity as occurs during AIDS, we hypothesized MAIDS mice will develop bilateral retinitis and clinical encephalitis following uniocular inoculation with HSV-1 due to unrestricted virus spread.

Methods : The KOS (laboratory) strain of HSV-1 or the H299 (ARN clinical isolate) of HSV-1 was injected into the anterior chamber of the right eye of healthy C57BL/6 mice or C57BL/6 mice with MAIDS. Ten days later, the ipsilateral (inoculated) eyes and contralateral (uninoculated) eyes were collected from all animals and analyzed histopathologically. These findings were compared with amounts of detectable infectious virus found in ipsilateral eyes, contralateral eyes, and brains collected from parallel groups of animals. All animals were assessed for clinical encephalitis.

Results : Healthy C57BL/6 mice inoculated with either HSV-1 strain failed to develop retinitis in the ipsilateral or contralateral eye, and all remained free of clinical encephalitis. In contrast, ipsilateral eyes of both HSV-1 [KOS] and HSV-1[H299]-infected C57BL/6 mice with MAIDS developed a necrotizing retinitis associated with high amounts of intraocular infectious virus and with histopathologic features reminiscent of AIDS-related PORN. Surprisingly, these MAIDS mice failed to develop contralateral retinitis or clinical encephalitis, findings consistent with an inability to detect infectious virus in the brains or contralateral eyes.

Conclusions : Two different strains of HSV-1 (laboratory and ARN clinical isolate) produced a similar pattern of necrotizing retinitis consistent with PORN in the ipsilateral eye during MAIDS. Of greater interest was the surprising observation that both HSV-1 strains failed to spread to the brain or contralateral eye during MAIDS as predicted. The immune mechanism(s) that operates during MAIDS to prevent virus spread into the brain and protect the contralateral eye from retinitis is under investigation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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