Pathogenesis Study of Enterovirus Infection Using an Authentic Bioengineered Human Enteric System (I)

Many viruses enter host through enteric system and cause diverse diseases other than enteric symptoms. Enterovirus infection is a typical example. After the primary entry in enteric system, the virus would then traffic to other organs, such as skin, heart, or central nerve system. However, how enteroviruses propagate in gut and how they spread to other organs is unclear. This integrated program project aims to study the role of enteric system on enterovirus infection using an authentic bio-engineered human enteric system. The constructed enteric tissue comprises different cell types including epithelial, muscle, nerve and blood vessel cells, which allow us not only to investigate the effects of virus infection in different cell populations at the same time but also examine the interactive networks in response among these cells. There are five component projects as following: (1) construction of bio-engineered 3D intestinal tissue for investigation of enteric infection, (2) dissecting host gene pathways involved in enterovirus infection/propagation in bio-engineered intestine tissue culture, (3) investigation of the dysregulation of antiviral response during enteroviral infection in bio-engineered intestine tissue culture by proteomics approaches, (4) receptor profiling and intervention of enterovirus infection in human enteric microsystem and (5) animal study of the role of enteric system in enterovirus infection –a xenograft (bio-engineered intestine tissue) animal model. This program project would allow us to study the pathogenesis of enterovirus infection at the molecular and cellular level, the organismal level and in a xenografted animal model. In contrast to the cancer tissue-derived cell lines, the enteric microsystem we used would behave like bona fide normal cells and exhibit biological responses to external stresses, which make them more like the authentic normal situation. Such study would provide valuable information to understand the pathogenesis of virus infection through gut entry - how enterovirus expand and traffic in host, and pave a way to develop effective therapeutic strategies.

Project ID:PC10408-1251
External Project ID:MOST104-2632-B182-002