ASTROCYTE-TARGETED EXPRESSION OF IFN-ALPHA-1 PROTECTS MICE FROM ACUTEOCULAR HERPES-SIMPLEX VIRUS TYPE-1 INFECTION

Type I IFNs (i.e., IFN-alpha and IFN-beta) play a key role in the host 's innate defense against viral pathogens. To examine the biologic rel evance of IFN-alpha to a viral pathogen within the confines of the ner vous system, IFN-alpha 1 transgenic mice whose transgene is under the control of the glial fibrillary acidic protein promoter (GFAP-IFN-alph a, astrocyte specific) were examined for resistance to an ocular herpe s simplex virus type 1 (HSV-1) infection. GFAP-IFN-alpha mice expresse d significantly higher levels of IFN-alpha beta (533 U) in the trigemi nal ganglion compared with nontransgenic mice (70 U) 72 h postinfectio n that corresponded with a significant reduction in the mRNA expressio n of the HSV-1 immediate early gene infected cell polypeptide 27 and l ate gene VP16, as well as the chemokines monocyte-chemoattractant prot ein-1 and cytokine response gene-2 in the eye and trigeminal ganglion. Six days postinfection, the viral load and the expression of infected cell polypeptide 27, CD8, RANTES, IFN-gamma, and IFN-alpha mRNA level s were reduced in the trigeminal ganglion of GFAP-IFN-alpha mice compa red with the wild-type mice. Following the establishment of HSV-1 late ncy (i.e., 30 days postinfection), only one of nine (11%) GFAP-IFN-alp ha mice was found to be latent compared with seven of eight (88%) of t he wild-type mice, as determined by the expression of the latency-asso ciated transcript RNAs, Likewise, only three of nine GFAP-IFN-alpha mi ce screened showed seroconversion by day 30 postinfection compared wit h nine of ten wild-type mice screened. Collectively; the results show that the IFN-alpha 1 transgenic mice are less susceptible to acute HSV -1 infection and the establishment of viral latency.