DETERMINANTS OF EPSTEIN BARR VIRUS MUCOSAL PATHOGENESIS

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DESCRIPTION: The applicant proposes to determine the role of epithelial cell polarity in infection by EBV. Little is known about the early, molecular or otherwise, events in EBV infection, when a transient epithelial phase of infection is presumed to occur or what favors the appearance of epithelial diseases such as OHL, NPL or Burkitt's lymphoma associated with EBV. In preliminary results the applicant provides data to suggest that epithelial cell polarity may play a role, whether the uptake of EBV is mediated by the EBV receptor CR2 or by IgA modulation of infection. To address this issue the applicant has developed a MDCK cell line transformed with either (i) CDNA encoding the rabbit polymeric immunoglobulin receptor (pIgR) or (ii) CD21 (CR2) CDNA expression vector (PR4 CR2). These matched MDCK cell transformants will allow the investigators to follow the fate of EBV strains Bas.8 P3HR-1K and Akata following entry of epithelial cells by each pathway ie CR2 mediated or through IgA modulation. The investigators can examine the transcriptional program and fate of virion DNA as well as cell morphology and physiology via viral infection through both routes of entry. The investigators plan to determine whether EBV induces interleukin-10 (Il-10) in epithelial cells by ELISA, biological essays and eventually RT-PCR in collaboration.