Perforin pathway is essential for protection of mice against lethal ocular HSV-1 challenge but not corneal scarring.
Perforin (cytolysin; pore-forming protein) is expressed in both CD8(+) cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and is a major factor responsible for the cytolytic activities of these cells. Both CD8(+) T-cells and NK cells are important in eliminating cells infected with certain viruses. We examined the role of perforin in a mouse model of HSV-1 infection using perforin-deficient mice. Naïve perforin knockout (perforin(0/0)) mice were more susceptible to lethal HSV-1 ocular challenge (60% survival), than naïve parental C57BL/6 (100% survival). In contrast, both C57BL/6 and perforin(0/0) mice had similar levels of HSV-1 induced corneal scarring. Vaccination of perforin(0/0) mice induced a significantly higher HSV-1 neutralizing antibody titer than vaccination of C57BL/6 mice, and the mice were completely protected against lethal ocular challenge. These results suggest that in naïve mice ocularly challenged with HSV-1, the perforin pathway was involved in protection against death, but not in protection against corneal scarring.
Ghiasi
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H
Ophthalmology Research, Cedars-Sinai Burn and Allen Research Institute, Los Angeles, CA 90048, USA. ghiasi@csmc.edu
Cai
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Perng
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Nesburn
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Wechsler
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D000818:Animals; D003315:Cornea / Q000473:pathology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D054353:Perforin