Involvement of STAT4 in IgG subtype switching and ocular HSV-1 replication in mice.
OBJECTIVE
To assess the relative impact of elevated T-helper 2 (T(H)2)- and reduced T-Helper 1 (T(H)1)-dependent immune responses on ocular herpes simplex virus type 1 (HSV-1) infection.


METHODS
Signal transducer and activator of transcription protein 4 knockout mice (BALB/c-STAT4(-/-)) and wild-type BALB/c control mice were immunized with avirulent HSV-1 strain KOS or were mock-immunized. Three weeks after the third immunization, neutralizing antibody titers were determined by plaque reduction assays. Following ocular infection with virulent HSV-1 strain McKrae, viral replication in the eye, blepharitis, corneal scarring (CS), survival, and immunoglobulin (Ig) isotypes in sera were determined.


RESULTS
Vaccinated STAT4(-/-) and BALB/c mice contained significant and similar neutralizing antibody titers and were completely protected against HSV-1-induced death and CS. In contrast to vaccinated STAT4(-/-) mice, mock-vaccinated STAT4(-/-) mice had higher ocular HSV-1 titers than mock-vaccinated BALB/c mice on days 2-3 post-ocular infection. There were also significant differences in the levels of IgG2a, IgG2b, and IgG3 in the sera of STAT4(-/-) mice when compared to the control BALB/c mice.


CONCLUSIONS
These results suggest that the absence of T(H)1 cytokine responses did alter protection against viral replication and IgG isotypes but not eye disease or survival.
Allen
Sariah J
SJ
Department of Surgery, CSMC Burns & Allen Research Institute, Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, Los Angeles, CA 90048, USA.
Mott
Kevin R
KR
Ghiasi
Homayon
H
D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology; D001762:Blepharitis / Q000150:complications / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D002921:Cicatrix / Q000097:blood / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D003315:Cornea / Q000473:pathology; D005123:Eye / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000097:blood / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D050797:STAT4 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D016019:Survival Analysis; D014611:Vaccination; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007132:Immunoglobulin Isotypes; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse