Southern Group Research Summary: Microbial Infections at Human Mucosal Surfaces
We have developed ex vivo experimental systems to study transmission and initiation of human microbial infections. Our procedures rely on short-term human organ cultures and primary human cell populations. We have worked for many years with the human retroviruses, human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1) that are transmitted either vertically or horizontally in human populations. Standard experimental formats allow study of essential parameters, in both the donor and recipient of infectivity, that impact on the overall probability of transmission. Insight into the specific processes of transmission can contribute to evaluation of preventative and protective interventions to diminish transmission. In the course of working with human tissue samples, we realized that "normal tissue" represents a broad range of conditions and that pre-existing infections must be recognized as contributory factors for susceptibility to de novo infections. Active, seemingly asymptomatic infections with human herpes virus 6 (HHV-6) and one or more human polyomaviruses (HPyV) have been detected in the majority of colon, palatine tonsil and premenopausal cervix samples in the Southern Group tissue collection. Additionally, we have derived several spontaneously immortalized B cell lines supporting latent Epstein Barr virus (EBV) infection and have a unique patient-derived B cell population that sustains cytolytic EBV infection. Collectively, the human ex vivo experimental systems provide a foundation for human-based studies that can be utilized for all types of microbial infections with the recognition of biologically relevant polymicrobial conditions.