Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma
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Updated: Aug 6, 2026
Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Srikumar Sengupta1, Johan A den Boon, I-How Chen
1Institute for Molecular Virology, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
Abstract:
To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA1, EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes. Among the human genes whose inhibition was most strongly correlated with increased EBV gene expression were multiple MHC class I HLA genes involved in regulating immune response via antigen presentation. The association between EBV gene expression and inhibition of MHC class I HLA expression implies that antigen display is either directly inhibited by EBV, facilitating immune evasion by tumor cells, and/or that tumor cells with inhibited presentation are selected for their ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene-mediated tumor-promoting actions. Our data clearly reflect such tumor promotion, showing that deregulation of key proteins involved in apoptosis (BCL2-related protein A1 and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP, SCYL1, and NIN), and metastasis (matrix metalloproteinase 1) is closely correlated with the levels of EBV gene expression in NPC.
Insights
Epstein-Barr virus (EBV) gene expression in nasopharyngeal carcinoma (NPC) correlates with suppressed immune response and tumor-promoting gene activity. This suggests EBV drives cancer progression by evading immune detection and disrupting normal cellular functions.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Nasopharyngeal carcinoma (NPC) is an epithelial cancer associated with Epstein-Barr virus (EBV).
- The molecular mechanisms maintaining EBV-associated NPC are not fully understood.
- Understanding these mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying EBV-associated NPC maintenance.
- To correlate EBV gene expression with host gene expression in NPC tissues.
- To identify host genes and pathways modulated by EBV in NPC.
Main Methods:
- Global gene expression profiling of 31 laser-captured NPC tissues and 10 normal nasopharyngeal tissues.
- Measurement of latent EBV gene expression (EBNA1, EBNA2, EBNA3A, EBNA3B, LMP1, LMP2A).
- Correlation analysis between viral and host gene expression levels.
Main Results:
- Gene expression profiles clearly distinguished NPC tumors from normal tissues.
- EBV gene expression levels were inversely correlated with a significant subset of host genes.
- Inhibition of MHC class I HLA genes, involved in immune response, strongly correlated with increased EBV gene expression.
- Deregulation of apoptosis, cell cycle, and metastasis-related genes was closely correlated with EBV gene expression levels.
Conclusions:
- EBV likely facilitates immune evasion in NPC by inhibiting antigen presentation (MHC class I HLA expression).
- EBV promotes tumor growth by deregulating host genes involved in apoptosis, cell cycle control, and metastasis.
- These findings elucidate key molecular mechanisms of EBV-driven NPC pathogenesis.
