Herpes Simplex Virus-2 Pathogenesis

Herpes simplex virus-2 (HSV-2) is the leading cause of genital ulcers worldwide, an important risk factor for HIV acquisition and transmission, and a cause of severe disease in immunosuppressed individuals and infants. No effective, licensed vaccine exists for HSV-2 in humans, and existing antiviral therapies are only partially effective.

Accessibility of the skin and mucosal tissues where HSV-2 replicates has allowed for frequent sampling to measure viral levels and immune responses, enabling the completion of complex and informative studies of this fascinating virus.

Through a strategic combination of human studies, animal models, and mathematical modeling, our group has advanced scientific understanding of the complex interactions between HSV-2 and the host. Specifically, we demonstrated that viral shedding episodes occur almost weekly but are extraordinarily variable over time and space. HSV-2 is often eliminated in just a few hours and is shed without symptoms, but some episodes cause uncomfortable lesions and persist for more than a week. The immune response, characterized by dense sheets of CD8+ and CD4+ T cells, is intense but highly localized to micro-regions where viral levels were previously high.

Our mathematical models help explain high episode frequency and diversity, as well as the observed spatial features of shedding and the immune response. These studies will help identify the density and type of T cells necessary for an effective vaccine.

HSV-2 pathogenesis
HSV-2 pathogenesis