Genital herpes, which is caused by the herpes simplex virus (HSV), is a lifelong infection with periods of latency and flare-up. During latency, the virus lies dormant in nerve cells in the genitals, and during reactivation, the virus traffics from these nerve cells to genital skin cells, where it replicates and can sometimes cause painful lesions. Whether the reactivation is clinical, meaning that noticeable symptoms such as lesions occur, or subclinical, meaning that replicating virus is present in the genital skin cells but the person feels no symptoms, the immune system eventually clears the virus from the skin cells and the infection goes back to its latent phase. Researchers have recently noticed that in each HSV-infected person, reactivation episodes range widely in terms of amount of replicating virus present in the genitals, severity of symptoms, and duration of the episode. Such variations can occur rapidly, so that in the span of a few weeks or months, an individual might have several episodes of varying length and severity.
To address the possible reasons behind this variability, VIDD clinical research associate Dr. Josh Schiffer and colleagues expanded their previous mathematical model of HSV infection. In the model, which was built off experimental data of 1,003 shedding episodes from 386 infected people, the researchers varied either immune cell density at episode onset or amount of virus released from neurons, and followed natural expansion and decay of immune cells (specifically, CD8+ T-cells) present in the genital skin, and asked which of these variables had a greater effect on episode severity and duration. They found that immune cell density at episode onset had by far a larger influence on episode variability. In contrast, making the amount of virus released from neurons a thousand times larger had very little effect on episode severity in the model. In addition, even small decreases in infected cell lifespan (40 minutes) due to increased T-cell density resulted in a change from symptomatic lesions to asymptomatic shedding, and a corresponding reduction of the number of infected epithelial cells from more than 100,000 to just a few cells. These findings hint that therapies aimed at increasing immune cell density in the genital mucosa may be a fruitful path to more effectively diminish HSV reactivation.
Schiffer JT, Abu-Raddad L, Mark KE, Zhu J, Selke S, Koelle DM, Wald A, Corey L. Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18973-8.