Astrocyte-targeted expression of IFN-alpha1 protects mice from acute ocular 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 relevance of IFN-alpha to a viral pathogen within the confines of the nervous system, IFN-alpha1 transgenic mice whose transgene is under the control of the glial fibrillary acidic protein promoter (GFAP-IFN-alpha, astrocyte specific) were examined for resistance to an ocular herpes simplex virus type 1 (HSV-1) infection. GFAP-IFN-alpha mice expressed significantly higher levels of IFN-alphabeta (533 U) in the trigeminal ganglion compared with nontransgenic mice (70 U) 72 h postinfection that corresponded with a significant reduction in the mRNA expression of the HSV-1 immediate early gene infected cell polypeptide 27 and late gene VP16, as well as the chemokines monocyte-chemoattractant protein-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 levels were reduced in the trigeminal ganglion of GFAP-IFN-alpha mice compared with the wild-type mice. Following the establishment of HSV-1 latency (i.e., 30 days postinfection), only one of nine (11%) GFAP-IFN-alpha mice was found to be latent compared with seven of eight (88%) of the wild-type mice, as determined by the expression of the latency-associated transcript RNAs. Likewise, only three of nine GFAP-IFN-alpha mice screened showed seroconversion by day 30 postinfection compared with nine of ten wild-type mice screened. Collectively, the results show that the IFN-alpha1 transgenic mice are less susceptible to acute HSV-1 infection and the establishment of viral latency.
Carr
D J
DJ
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Veress
L A
LA
Noisakran
S
S
Campbell
I L
IL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004198:Disease Susceptibility; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D016849:Keratitis, Herpetic / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D017735:Virus Latency
D005904:Glial Fibrillary Acidic Protein; D016898:Interferon-alpha; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins