Virologic and immunologic evidence of multifocal genital herpes simplex virus type 2 infection.

Publication Type:

Journal Article

Source:

Journal of virology, Volume 88, Issue 9, p.4921-31 (2014)

Keywords:

2014, Center-Authored Paper, Immune Monitoring Core Facility, March 2014, Shared Resources, Vaccine and Infectious Disease Division

Abstract:

Genital HSV reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized.To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2 seropositive persons. HSV was detected via PCR and sites of asymptomatic HSV shedding were biopsied within 24 hours. CD4+ and CD8+ T cells were quantified by immunofluorescence, and HSV specific CD4+ T cells were identified by intracellular cytokine cytometry.HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range 0-22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (p<0.001). In biopsies of asymptomatic shedding sites, we found increased numbers of CD8+ T cells compared to control tissue (27 vs. 13 cells/mm(2), p=0.03) and identified HSV specific CD4+ T cells.HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV-specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.