PERSISTENT CYTOKINE EXPRESSION IN TRIGEMINAL GANGLION LATENTLY INFECTED WITH HERPES-SIMPLEX VIRUS TYPE-1

Following ocular infection, herpes simplex virus type 1 (HSV-1) establ ishes latency in trigeminal ganglion (TG) neurons, Using reverse trans cription-PCR, cytokine gene expression was analyzed in the TGs of mice infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mR NAs were readily detected in TGs taken from mice 7 days postinoculatio n (PI), Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detect ed by ELISA of TC homogenates. Between 5 and 45 days PI, IL-10, IFN-ga mma, TNF-a, and RANTES mRNAs were detected in nearly 100% of: latently infected TGs (latent infection was confirmed by reverse transcription -PCR detection of HSV-1 latency-associated transcripts), T cell-associ ated cytokine and chemokine mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the majority of latently infected TG samples t aken between 60 and 135 days PI, In contrast, these cytokine mRNA spec ies were rarely detected in uninfected TGs. Measurement of serum Abs t o HSV-1 at different times revealed that anti-HSV-l Ab concentrations approached a plateau in mice by 30 days PI but remained at high levels 67 and 125 days PI. Although there was molecular evidence of an ongoi ng immune response to HSV-1 in latently infected TC, histologic analys is indicated that very few mononuclear cells remained in the ganglion 60 days PI. Collectively, the results suggest that residual lymphocyte s encounter viral Ag during HSV-1 latency with sufficient frequency to remain activated. The paradox of a persistent immune response against a latent infection is discussed.