Using Imaging Approaches to Gain Mechanistic Insights into HIV Transmission and Prevention
Thomas J. Hope Northwestern University, Feinberg School of Medicine, Department of Cell and Molecular Biology, Chicago, IL
Over the past 20 years my laboratory has developed a series of imaging based tools that allow the imaging of individual HIV particles as they interact with cells and tissues and intact mucosal barriers in the rhesus macaque model. Although these studies defined potential paths of viral penetration through mucosal barriers to encounter would-be target cells, the role of paths for sexual transmission was unclear. Therefore, we developed a single round dual reporter SIV vector system that allows the macroscopic identification of the initial sites of infection after Mucosal challenge. This system works well in the study of the portal of transmission revealing that Th17 cells and immature dendritic cells (iDC) are the major first targets of vaginal and rectal transmission. Importantly, this reporter system identifies sites of mucosal barrier disfunction and therefore identifies sites of SIV replication in a mixed challenge experiment. The study of these early foci of transmission reveal a highly dynamic environment where innate host responses to the local SIV replication can be documented as soon as 48 hours after challenge. We have recently adapted our systems using fluorescently tagged virions and antibodies to allow their detection by whole animal Positronic Emission Tomography (PET) to study the distribution of virions and antibodies in the context of the anatomy and physiology of a living macaque.