Role of dendritic cells in enhancement of herpes simplex virus type 1 latency and reactivation in vaccinated mice.
Ocular infection with herpes simplex virus type 1 (HSV-1) frequently leads to recurrent infection, which is a major cause of corneal scarring. Thus, the prevention of the establishment of latency should be a primary goal of vaccination against HSV-1. To this end, we have examined the contribution of dendritic cells (DCs) to the efficacy of a vaccine against ocular HSV-1 infection. Transgenic mice (expressing a CD11c-diphtheria toxin receptor-green fluorescent protein construct) with a BALB/c background were immunized with a vaccine consisting of DNA that encodes five HSV-1 glycoproteins or were immunized with vector control DNA. The vaccinated mice were then depleted of their DCs through the injection of diphtheria toxin before and after ocular challenge with HSV-1. Analyses of HSV-1 replication in the eye, blepharitis, corneal scarring, and the survival of the infected mice upon primary infection indicated that DC depletion neither promoted nor compromised the efficacy of the vaccine. In contrast, DC depletion was associated with an approximately fivefold reduction in the level of latent virus in the trigeminal ganglia (TGs) of latently infected mice, as well as a significant reduction in the reactivation rate of latent virus. The possibility that DCs enhance the latency of HSV-1 in the TGs of ocularly infected mice suggests for the first time that DCs, rather than acting as "immune saviors," can exacerbate disease and compromise vaccine efficacy by enhancing viral latency and reactivation.
Mott
Kevin R
KR
Center for Neurobiology and Vaccine Development, D2024, Cedars-Sinai Burns and Allen Research Institute, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Ghiasi
Homayon
H
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D004167:Diphtheria Toxin / Q000494:pharmacology; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012668:Trigeminal Ganglion / Q000276:immunology / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D004167:Diphtheria Toxin; D022301:Herpes Simplex Virus Vaccines; D019444:Vaccines, DNA