MECHANISMS OF VIRUS SPREAD AND INNATE RESPONSES TO INFECTION IN SOLID TISSUES MAINTAINED EX VIVO

Despite extensive studies of viral infection and spread, using tissue culture cells or animal models, our understanding of virus interactions with the clinically-relevant target tissues is limited. To study viral interactions within a complex three-dimensional solid tissue, we have developed an ex vivo experimental model, consisting of the native target tissues, obtained from the surgery room, and maintained as organ cultures. In this presentation, two herpes viruses, HSV1 and HCMV, will be discussed in relation to their target tissues in human. HSV1 usually infects the skin, causing sour blisters, and occasionally spread to the brain to trigger encephalitis. Infection of these two target tissues ex vivo demonstrated different modes of HSV1 infection and spread and unique tissue-specific innate responses. HCMV is a leading cause of congenital infection affecting ~1% of live newborns. Transfer of HCMV form the mother through the placenta is key determinant of congenital infection. To study this type of infection, we have developed an organ culture from the decidual tissue, a multicellular structure at the interface between the mother and the fetus. HCMV infection of the decidual tissue ex vivo provided a novel system to analyze the mode of virus transmission to the fetus and of the immune responses to the infection. Taken together, the organ culture methodology presents a new approach in the analysis of viral infection and pathogenesis and is applicable in the screening of new antiviral drugs.