Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults

Abstract

Background: Herpes simplex virus (HSV) remains latent in nerve root ganglia of infected persons and is thought to reactivate several times yearly. Recent in situ data show the localization of HSV-specific CD8(+) T cells at the dermal epidermal junction next to peripheral sensory nerve endings, suggesting that viral reactivation may occur more frequently than previously appreciated.

Methods: Twenty-five HSV-2-seropositive and 18 HSV-1-seropositive healthy adults collected anogenital and oral swabs, respectively, 4 times per day for 60 days. Swabs were assayed for HSV, using a quantitative polymerase chain reaction assay.

Results: Twenty-four percent of anogenital reactivations and 21% of oral reactivations lasted < or =6 h, and 49% of anogenital reactivations and 39% of oral reactivations lasted < or =12 h. Lesions were reported in only 3 (7%) of 44 anogenital reactivations and 1 (8%) of 13 oral reactivations lasting < or =12 h. The median HSV DNA levels at initial and last detection were 10(3.5) and 10(3.3) copies/mL, respectively, during anogenital reactivation and 10(3.7) and 10(3.0) copies/mL, respectively, during oral reactivation.

Conclusions: This high frequency of short subclinical HSV reactivation in immunocompetent hosts strongly suggests that the peripheral mucosal immune system plays a critical role in clearing HSV reactivations.

Figure 1

Rates of herpes simplex virus shedding for 72 genital and 33 oral episodes of known duration. A, Rates of genital shedding (black) and oral shedding (grey), by sampling time point. B, Duration of genital shedding episodes. C, Duration of oral shedding episodes.

Figure 2

Herpes simplex virus levels for 72 genital and 33 oral episodes of known duration, by durations of genital (A) and oral (B) shedding episodes.

Figure 3

Representative herpes simplex virus (HSV) shedding patterns for 3 participants. Negative values indicate missing samples. A, Data for a 27-year-old woman, HSV-1 and HSV-2 seropositive, with genital herpes diagnosed just before study entry. All pictured genital reactivations are HSV-2 except the 7-h reactivation on day 16, during which HSV-1 was detected. B, Data for a 50-year-old man, HSV-1 and HSV-2 seropositive, with genital herpes diagnosed 25 years before study entry. All pictured genital reactivation episodes are HSV-2, except 1 swab specimen collected at 1 time point on day 41, had both HSV-1 and HSV-2 detected. C, Data for a 35-year-old man, HSV-1 seropositive, with oral herpes diagnosed 5 years before study entry.