Kathy Shair: Discoveries of Epstein-Barr virus molecular pathogenesis and biomarker for risk assessment of nasopharyngeal carcinoma

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Here is the link to the webinar: https://gu-se.zoom.us/j/69425328760

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Speaker: Kathy Shair, University of Pittsburg, USA

Topic:

The nasopharyngeal tissue is composed of pseudostratified and stratified epithelia, which can be modeled in three dimensional (3-D) cell culture. The progenitor cell for Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is unknown; however, both latent and lytic infection are thought to be important in preneoplastic mechanisms and are intimately tied to cellular differentiation. Developing 3-D cell culture models of the nasopharyngeal epithelium is a critical step in defining EBV molecular pathogenesis in NPC. We have developed two distinct 3-D cell culture methods using conditionally reprogrammed cells from the nasopharynx, that are susceptible to de novo EBV infection: (1) a pseudostratified air-liquid interface (pseudo-ALI) model to study respiratory epithelia and, (2) an organotypic raft model to study the stratified epithelium. In both models, cells in 3-D culture are exposed to EBV inoculum by co-culture with anti-human IgG-reactivated EBV-positive B-cell inoculum. We demonstrate that EBV latent and lytic infection can be identified in these 3-D culture models, that donor variation exists, and that the infection program can be distinguished by cell types using immunostaining and single cell RNA-sequencing. With these new approaches, we demonstrate that pseudostratified cultures can be generated from persons undergoing skull base surgery (with no sinus co-pathology), as well as from patients undergoing surgery in the sinus clinic. Thus, these new 3-D cell culture models can be used to identify susceptible cell types, and to study the molecular determinants of EBV pathogenesis in the nasopharynx, in persons with or without disease pathology in the upper airway.

http://www.mvm.pitt.edu/node/638

Host: Ka-Wei Tang, Dep. of Biomedicine

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