Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response.
The majority of trigeminal ganglia (TGs) are latently infected with alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very rarely. The goal of this study was to determine whether herpesvirus latency is linked to a local immune cell infiltration in human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42 examined TGs from 21 healthy individuals. The presence of immune cells correlated constantly with the occurrence of the HSV-1 latency-associated transcript (LAT) and only irregularly with the presence of latent VZV protein. In contrast, uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma, tumor necrosis factor-alpha, IP-10, and RANTES transcripts were significantly induced in TGs latently infected with HSV-1 but not in uninfected TGs. The persisting lymphocytic cell infiltration and the elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the first time that latent herpesviral infection in humans is accompanied by a chronic inflammatory process at an immunoprivileged site but without any neuronal destruction. The chronic immune response seems to maintain viral latency and influence viral reactivation.
Theil
Diethilde
D
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. dtheil@brain.nefo.med.uni-muenchen.de
Derfuss
Tobias
T
Paripovic
Igor
I
Herberger
Simone
S
Meinl
Edgar
E
Schueler
Olaf
O
Strupp
Michael
M
Arbusow
Viktor
V
Brandt
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D003199:Computer Systems; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology* / Q000503:physiopathology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000821:virology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D017735:Virus Latency
C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C477253:latency associated transcript, herpes simplex virus-1