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Minoru Tanigawa, John E. Bigger, Maria Y. Kanter, Sally S. Atherton; Natural Killer Cells Prevent Direct Anterior-to-Posterior Spread of Herpes Simplex Virus Type 1 in the Eye. Invest. Ophthalmol. Vis. Sci. 2000;41(1):132-137.
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purpose. Anterior chamber (AC) inoculation of the KOS strain of herpes simplex
virus type 1 (HSV-1) results in morphologic sparing of the ipsilateral
retina, whereas the retina of the uninoculated contralateral eye
becomes infected and undergoes acute retinal necrosis. Natural killer
(NK) cells are an important component of the primary immune response to
most virus infections. The purpose of this study was to determine
whether NK cells are involved in preventing early direct
anterior-to-posterior spread of HSV-1 after AC inoculation.
methods. Normal BALB/c mice were inoculated with 4 × 104 plaque-forming units (PFU) of the KOS strain of HSV-1 using the AC
route. NK activity was measured in the spleen, the superficial cervical
and submandibular lymph nodes, and the inoculated eye by lysis of
chromium-labeled, NK-sensitive YAC-1 target cells. Histopathologic
scoring and immunohistochemical staining for HSV-1 were performed in
NK-depleted (injected intravenously with anti-asialo GM1)
or mock-depleted (injected intravenously with normal rabbit serum)
results. In mock-depleted mice, NK activity in the spleens, superficial cervical
and submandibular lymph nodes, and inoculated eyes peaked at
postinoculation (pi) day 5 and declined by pi day 7. Treatment with
anti-asialo GM1 eliminated NK activity in the eye and at
nonocular sites. The histopathologic scores at pi day 5 indicated more
damage to the retinas of NK-depleted mice than to those of
mock-depleted mice, and immunohistochemical staining for HSV-1 showed
spread of the virus to the sensory retina only in NK-depleted mice.
conclusions. NK cells were activated within 5 days after AC inoculation of the KOS
strain of HSV-1. Activation of NK cells appears to play a role in
preventing direct anterior-to-posterior spread of the virus in the
inoculated eye which, in turn, protects the retina of this eye and
helps to explain why the architecture of the retina of this eye is
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