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Interferon production in inbred mice during herpetic eye disease
Abstract:
Low levels (less than 5 units/eye) of interferon (IFN) were detected in the eyes of BALB/c and C57BL/6 mice one to five days after instillation of 10(7) pfu/eye of herpes simplex virus type 1 (HSV) onto scarified corneas. This dose of virus produced herpetic keratitis characterized by dendritic epithelial lesions one day post infection in both strains of mice. The disease progressed to severe necrotizing stromal keratitis in the eyes of all BALB/c mice, but only three of 10 eyes of C57BL/6 mice by 21 days after infection. Footpad immunization 30 days prior to ocular infection protected both strains from stromal disease, but did not enhance IFN production in the eye. At lower inoculating doses of virus (less than or equal to 10(5) pfu/eye), C57BL/6 mice showed greater resistance to stromal disease and produced less virus over a shorter period of time than BALB/c mice. No IFN was detected at any time after infection with doses of virus less than 10(7) pfu/eye, nor was IFN detected in plasma of any infected mice. The failure to detect high levels of IFN in homogenates of eyes did not reflect an inability of ocular tissues to produce IFN since IFN-beta was detected as early as two hours after topical treatment with the potent IFN inducer, carboxymethylacridanone (CMA). The two mouse strains produced similar levels of IFN in the eye in response to CMA. These data indicated that the relative resistance of mice to HSV eye infection was not related to the rapid local production of IFN, nor was resistance related to systemic IFN production in plasma or spleen.
Insights
Herpes simplex virus type 1 (HSV) keratitis severity in mice is not linked to interferon (IFN) levels. Resistance to HSV eye infection depends on factors other than rapid local or systemic IFN production.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV) causes herpetic keratitis, an eye infection.
- Interferon (IFN) is a key antiviral cytokine, but its role in HSV ocular infections is not fully understood.
- Mouse models are crucial for studying viral keratitis and immune responses.
Purpose of the Study:
- To investigate the role of interferon (IFN) in the pathogenesis of herpes simplex virus type 1 (HSV) keratitis in different mouse strains.
- To determine if local ocular or systemic IFN production correlates with resistance to HSV-induced stromal keratitis.
- To compare the susceptibility of BALB/c and C57BL/6 mice to HSV ocular infection.
Main Methods:
- Instillation of HSV-1 onto scarified corneas of BALB/c and C57BL/6 mice.
- Monitoring for clinical signs of keratitis, including epithelial and stromal disease.
- Quantification of interferon (IFN) levels in ocular tissues and plasma.
- Assessment of IFN production following topical stimulation with carboxymethylacridanone (CMA).
Main Results:
- Both mouse strains developed herpetic keratitis, but BALB/c mice exhibited more severe stromal disease.
- Low levels of ocular IFN were detected early after high-dose HSV-1 infection, with no IFN in plasma.
- Pre-infection immunization protected against stromal keratitis but did not enhance ocular IFN production.
- C57BL/6 mice showed greater resistance to stromal disease and lower viral loads at lower infectious doses.
- Ocular tissues could produce IFN-beta in response to a chemical inducer, indicating functional IFN-producing capacity.
Conclusions:
- Relative resistance to HSV eye infection in mice is not associated with rapid local or systemic interferon (IFN) production.
- Factors beyond IFN production likely determine the severity of HSV-induced stromal keratitis.
- Mouse strain differences in susceptibility to HSV keratitis may involve mechanisms independent of IFN response.