title: Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye.
abstract: OBJECTIVE
  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 X 10(4) 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) mice.
  
  
  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 spared.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 78229-3900, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tanigawa
authors.forename: J E
authors.initials: JE
authors.lastname: Bigger
authors.forename: M Y
authors.initials: MY
authors.lastname: Kanter
authors.forename: S S
authors.initials: SS
authors.lastname: Atherton
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000821:virology*; D015828:Eye Infections, Viral / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012164:Retinal Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D007074:Immunoglobulin G; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside