23 September 2020
Controlling reactivation of herpes simplex virus-2
Published online 21 October 2010
Herpes simplex virus-2 (HSV-2) poses a serious public health threat, causing recurring genital lesions that persist in the host. Incidence is associated with other severe diseases, such as meningitis and hepatitis, and it is a strong risk factor for HIV infection.
After the primary infection, the virus invades nerve cells, where it can quietly reside. The virus can reactivate anytime and then target epithelial cells. The recurrence rate and severity of episodes, even in one person, varies considerably with no definite reason.
A team of researchers from the University of Washington, the Fred Hutchinson Cancer Research Center and Weill Cornell Medical College in Qatar created a mathematical model to study what conditions prompt sporadic episodes.
They found that the severity of a recurrent attack is not determined by the amount of virus released from the nerve terminals, but by the concentration of CD8+ T cells located at the site during the onset of reactivation. When concentration is high enough, CD8+ T cells quickly destroy infected cells before their population expands to a level that would allow for a severe episode. A thousand folds increase in the quantity of HSV-2 released had little effect on the severity of an attack. A slight decrease in CD8+ T-cells concentration can give the virus enough time to infect several thousand cells, which can lead to a prolonged episode.
The researchers suggest that a HSV-2 vaccine that increases the concentration of CD8+ T cells at mucosal surfaces may help control virus reactivation and decrease consequent clinical symptoms.
- Schiffer, J. et al. Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes. PNAS 18 Oct 2010. doi: doi:10.1073/pnas.1006614107