Transgenic expression of interleukin-6 in the central nervous system confers protection against acute herpes simplex virus type-1 infection.
IL-6 is a pro-inflammatory cytokine that has previously been associated with herpes simplex virus type 1 reactivation. To further investigate this relationship during acute infection, ocular HSV-1 infection was studied in transgenic mice homozygous or heterozygous expression of IL-6 by astrocytes in the central nervous system. The virus load in both the eye and trigeminal ganglia was significantly reduced at day 6 but not day 3 post infection in the homozygous IL-6 transgenic mice compared to the wild type and heterozygous littermates. IL-6 protein and mRNA levels in the eye coincided with the level of transgene expression in mice acutely infected with virus (i.e., day 3 post infection). Likewise, IL-6 transcript levels in the TG mirrored the expression of the transgene in the mice throughout the course of the infection into latency. The HSV-1 alpha lytic phase gene ICP27 was rapidly down-regulated by day 6 post infection in the TG of homozygous IL-6 transgenic mice compared to the wild type and heterozygous littermates. The resistance to acute HSV-1 infection in the homozygous IL-6 transgenic mice correlated with a significant elevation in IFN-alpha/beta in the eye compared to the wild type or heterozygous IL-6 transgenic animals. Heterozygous and homozygous IL-6 transgenic mice latently infected with HSV-1 showed elevated anti-HSV-1 antibody titers compared to the latently infected wild type controls. Collectively, the results suggest dose-dependent IL-6 antagonism of acute HSV-1 infection in vivo.
Carr
D J
DJ
Department of Microbiology, Immunology, and Parasitology, LSU Medical Center, New Orleans, Louisiana 70112, USA.
Campbell
I L
IL
D000208:Acute Disease; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014276:Trigeminal Nerve / Q000378:metabolism / Q000821:virology; D019562:Viral Load
D018946:Chemokine CCL5; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D016898:Interferon-alpha; D015850:Interleukin-6; D016899:Interferon-beta