Herpes simplex virus type 1 induction of chemokine production is unrelated to viral load in the cornea but not in the nervous system.

Herpes simplex virus type 1 elicits a strong host inflammatory response after corneal infection. The purpose of the current study was to compare the production of chemokines induced by viral infection at sites known to harbor virus after ocular inoculation in order to determine the relationship between viral load and chemokine expression. Using highly resistant IFN-alpha1 transgenic mice whose transgene is under the control of the glial fibrillary acidic protein promoter in comparison with the more sensitive wild-type counterparts, we compared the expression of chemokines versus the amount of infectious virus recovered from the anterior segment of the eye and nervous system. Consistent with our predicted outcome, the level of infectious virus recovered in the iris, trigeminal ganglia, and brainstem of resistant versus sensitive mice correlated with chemokine production; that is, the less virus recovered the less chemokine (CCL2, CCL3, CCL5, CXCL9, and CXCL10) produced. In contrast to the nervous system and iris, there was no correlation between chemokine expression and level of infectious virus recovered in the cornea. We interpret these results as suggesting chemokine expression within the cornea in response to herpes simplex virus type 1 infection is driven by factors other than antigenic stimulation.