TY - JOUR
T1 - Perforin pathway is essential for protection of mice against lethal ocular HSV-1 challenge but not corneal scarring
AU - Ghiasi, Homayon
AU - Cai, Steve
AU - Perng, Guey Cheun
AU - Nesburn, Anthony B.
AU - Wechsler, Steven L.
N1 - Funding Information:
This work was supported by Public Health Service grant EY09224 from the National Eye Institute to HG, the Discovery Fund for Eye Research, and the Skirball Program in Molecular Ophthalmology.
PY - 1999/12/15
Y1 - 1999/12/15
N2 - 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. Naive perforin knockout (perforin(0/0)) mice were more susceptible to lethal HSV-1 ocular challenge (60% survival), than naive 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 naive mice ocularly challenged with HSV-1, the perforin pathway was involved in protection against death, but not in protection against corneal scarring.
AB - 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. Naive perforin knockout (perforin(0/0)) mice were more susceptible to lethal HSV-1 ocular challenge (60% survival), than naive 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 naive mice ocularly challenged with HSV-1, the perforin pathway was involved in protection against death, but not in protection against corneal scarring.
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U2 - 10.1016/S0168-1702(99)00107-0
DO - 10.1016/S0168-1702(99)00107-0
M3 - Article
C2 - 10581382
AN - SCOPUS:0032726606
SN - 0168-1702
VL - 65
SP - 97
EP - 101
JO - Virus Research
JF - Virus Research
IS - 2
ER -