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In most of the associated tumors, the virus remains in a latently infected state. During latency, EBV expresses Latent Membrane Protein 2A (LMP2A) along with few other genes. We previously showed that LMP2A causes downregulation of HLA-ABC surface expression in EBV associated gastric carcinomas. However, the mechanism that leads to this downregulation remain unclear. We therefore analyzed methylation-mediated regulation of HLA-ABC expression by LMP2A. Interestingly, according to the \u2018missing self\u2019 hypothesis, when there is a decrease in HLA-ABC surface expression, expression of NKG2D ligands\u2019 must be upregulated to facilitate killing by Natural Killer (NK) cells. Analysis of NKG2D ligands\u2019 expression, revealed downregulation of MIC-A\/B surface expression in response to LMP2A. Furthermore, the role of Unfolded Protein Response (UPR) in the regulation of MIC-A\/B surface expression in cells expressing LMP2A was also investigated. Protein Disulfide Isomerase (PDI) mediated inhibition of MIC-A\/B surface expression was observed in LMP2A expressing cells. Our current findings provide new insights in LMP2A arbitrated dysregulation of host immune response in epithelial cell carcinomas.<\/jats:p>","DOI":"10.1038\/s41598-020-62081-0","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T11:03:32Z","timestamp":1585134212000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Downregulation of HLA-ABC expression through promoter hypermethylation and downmodulation of MIC-A\/B surface expression in LMP2A-positive epithelial carcinoma cell lines"],"prefix":"10.1038","volume":"10","author":[{"given":"Shweta","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subrata","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"62081_CR1","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S1357-4310(99)01451-3","volume":"5","author":"DJ Hicklin","year":"1999","unstructured":"Hicklin, D. 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