Herpes simplex virus type 1 infection of the mouse eye results
Herpes simplex virus type 1 infection of the mouse eye results in an impressive inflammatory response culminating in the death of the animal or the establishment of a latent infection depending on a number of ill-defined variables that include components of the innate and adaptive immune system. the establishment of an anti-viral environment by type I IFN transgenes. Type I IFN transgenes and IL-6 IL-6 is a pleiotropic cytokine produced in response to a number of viruses including lymphocytic choriomeningitis virus (7), Theilers murine encephalomyelitis virus (8), vesicular stomatitis virus (7), and herpes simplex virus (9, 10). The production of IL-6 has been linked to increased resistance to ocular HSV-1 infection (11, 12) perhaps acting as a chemoattractant for neutrophils (13) which are known to be involved in clearing virus from the eye (14,15). Previously, the transfection of mouse cornea with the IFN-1 transgene was found to increase IL-6 mRNA levels as measured by RT-PCR (6). We interpret these results to suggest that IL-6 may be a contributing factor in establishing an anti-viral environment following type I IFN exposure. To address this hypothesis, mice deficient in IL-6 Sitagliptin phosphate enzyme inhibitor (IL-6 KO) were transfected with the IFN-1 transgene and then characterized for resistance to ocular HSV-1 infection as measured by viral titer in the tear film and cumulative survival of infected mice. In the presence of the IFN-1 transgene, wild type mice showed a reduction in the viral load recovered in the tear film within the time frame of detectable virus during the acute infection (i.e., days 1C5 post infection) compared to the wild type group (C57BL/6) transfected with the plasmid construct alone (Fig. 2). The absence of IL-6 did not affect the outcome of viral yield in the tear film. Specifically, similar to the wild type mice, IL-6 KO mice transfected with the IFN-1 transgene also showed a reduction in the viral titer recovered in the tear film as well (Fig. 2). Therefore, from a local standpoint, the absence of IL-6 does not impact on the anti-viral efficacy of the IFN-1 transgene. Open in a separate window Figure 2 HSV-1 titer in the tear film at times post infectionWild type (C57BL/6, WT) and IL-6 deficient (IL6 KO) mice (n=10/group) were transfected with plasmid vector alone (Vect, 100 g/eye) or plasmid containing the IFN-1 transgene (IFN-a1, 100 g/eye) and infected with HSV-1 (1000 plaque forming units/eye, strain McKrae) 24 hr post transfection. At the time indicated immediately before (day 0) or after infection (day 1C7), mouse eyes were swabbed, and the swab was placed in media. The viral content within the media was determined by CCNU plaque assay using Vero cells. *p .05 comparing the IFN-1 transgene wild type (WT) or IL-6 deficient (IL6 KO) transfected groups to the control vector (Vect) transfected or non-transfected, vehicle (Veh)-treated Sitagliptin phosphate enzyme inhibitor group as determined by ANOVA and Tukeys post hoc t-test. The capacity to control viral replication within the cornea does not necessarily dictate the outcome of the infection. As the virus replicates within the cornea, it is also transported back into Sitagliptin phosphate enzyme inhibitor the ganglion via retrograde transport by innervated sensory processes that extend into the cornea (16). Within the ganglion (i.e., trigeminal ganglion, TG), the virus replicates and establishes a latent infection as well as travels to the central nervous system (CNS) where it continues to replicate. Although it is not entirely clear, it is thought that if the virus goes unchecked within the CNS the host (mouse) will succumb to the infection as a result of encephalitis. Therefore, it was necessary to determine if the.