Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus type-1-induced corneal scarring in various virus-mouse strain combinations.
OBJECTIVE
To determine whether the exacerbation of herpes simplex virus type-1 (HSV-1) induced corneal scarring that the authors reported previously in HSV-1 glycoprotein K (gK) vaccinated BALB/c mice challenged with HSV-1 strain McKrae was a general phenomenon independent of virus and mouse strains. To determine the gK-induced immune response leading to exacerbation of HSV-1-induced corneal scarring.


METHODS
BALB/c or C57BL/6 mice were vaccinated with gK, ocularly challenged with HSV-1 strain KOS or McKrae, and the relative amount of corneal scarring determined 28 days after challenge. The T cells, total serum, or purified immunoglobulin G (IgG) isolated from gK-vaccinated mice was transferred individually to naive mice, and the affects on corneal scarring after HSV-1 challenge were determined.


RESULTS
The KOS challenge of gK-vaccinated BALB/c mice resulted in significant corneal scarring (P = 0.0003), despite the fact that KOS normally produces no corneal scarring. McKrae challenge of gK-vaccinated C57BL/6 mice resulted in significant corneal scarring (P < 0.0001), despite the fact that C57BL/6 mice are normally refractory to HSV-1-induced corneal scarring. Passive transfer of total anti-gK mouse sera or purified anti-gK mouse IgG, but not adoptive transfer of total anti-gK T-cells to naive mice, resulted in exacerbation of corneal scarring after HSV-1 challenge (P < 0.0001). Mice defective for T-cell-dependent antibody production were not susceptible to exacerbation of HSV-1-induced corneal scarring by gK vaccination (P < 0.0001).


CONCLUSIONS
The ability of gK vaccination to exacerbate HSV-1-induced corneal scarring was not mouse strain or HSV-1 strain specific. The gK-induced exacerbation of corneal scarring was related to anti-gK IgG. How anti-gK IgG exacerbated HSV-1 induced corneal scarring remains to be determined.
Ghiasi
H
H
Cedars-Sinai Medical Center Research Institute, Los Angeles, California, USA.
Cai
S
S
Slanina
S
S
Nesburn
A B
AB
Wechsler
S L
SL
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D016367:Baculoviridae / Q000378:metabolism; D002921:Cicatrix / Q000473:pathology*; D003315:Cornea / Q000473:pathology*; D007074:Immunoglobulin G / Q000276:immunology; D016849:Keratitis, Herpetic / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018139:Simplexvirus / Q000235:genetics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D007074:Immunoglobulin G; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins