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

Publication Type:

Journal Article


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


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


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.