Herpes simplex virus-2 pathogenesis


In collaboration with Drs. Anna Wald, Christine Johnston and Lawrence Corey, we demonstrated that genital shedding episodes occur almost weekly but are extraordinarily variable over time and space.  On many occasions virus is eliminated in just a few hours and is shed without symptoms.  Yet, other episodes may persist for more than a week, and are associated with uncomfortable lesions. The local immune response, characterized by dense sheets of CD8+ and CD4+ T-cells, is intense but highly localized to micro-regions where viral levels are high.  With input from Drs. David Koelle and Jia Zhu, we have designed a range of clinical protocols, laboratory experiments and mathematical models to explain episode frequency and diversity, as well as observed spatial features of shedding and the immune response.  We remain intimately involved in protocol development that will further elucidate the pace of viral expansion and containment in different study populations.  These studies will help identify conditions necessary for an effective vaccine.

HSV-2 is a globally important infection that is the leading cause of genital ulcers worldwide, and is also a critical risk factor for HIV acquisition and transmission.  In addition, HSV can cause severe disease in persons with immunosuppression due to HIV, organ transplantation, stem cell transplantation, or other immuncompromised conditions.  Neonatal HSV infection is particularly severe and is a significant public health concern.  Existing antiviral therapies are highly useful but not completely effective.  Unfortunately, there is no licensed, effective vaccine for humans.

HSV-2 is also a fascinating disease to study.  Unlike many other important human viral infections, which replicate in deeper tissues, HSV-2 infection occurs in highly accessible skin and mucosal tissues. This allows for high frequency of sampling for virus as well as the human immune response to infection.  Our group uses a strategic combination of human studies, animal models, and mathematical modeling to better understand the complex interactions between virus and host.