Abstract
Epstein-Barr virus (EBV) is an opportunistic pathogen that can manifest itself as a potential contributor to human diseases years after primary infection, specifically in lymphoid and epithelial cell malignancies in immune-competent and immune-compromised hosts. The virus shuttles between B cells and epithelial cells during its infection cycle, facilitating its persistence and transmission in humans. While EBV efficiently infects and transforms B-lymphocytes, epithelial cells are not as susceptible to transformation in vitro. We utilized a 3D platform for culturing normal oral keratinocyte cells (NOKs) using Matrigel for greater insights into the molecular interactions between EBV and infected cells. We determined the transcriptome of EBV infected NOKs and peripheral blood mononuclear cells (PBMCs) for 7 and 15 days. LMPs (-1, -2A, and -2B) and EBNAs (-1, -2, -3A, -3B and -3C) were detected in all samples, and lytic gene expression was significantly higher in NOKs than PBMCs. We identified over 2000 cellular genes that were differentially expressed (P-value<0.05). Gene ontology (GO) and pathway analyses significantly identified pathways related to collagen-activation, chemokine signaling, immune response, metabolism, and antiviral responses. We also identified significant changes in metalloproteases and genes encoding chemotactic ligands and cell surface molecules. C-X-C chemokine receptor type 4 (CXCR4) was dramatically downregulated in PBMCs and upregulated in NOKs. However, MMP1 was significantly downregulated in NOKs and upregulated in PBMCs. Therefore, multiple pathways contribute to distinct pathologies associated with EBV infection in epithelial and B cells, and MMP1 and CXCR4 are critical molecules involved in regulation of latent and lytic states linked to viral associated diseases.