Abstract

Epstein–Barr virus (EBV) is a common human pathogen that infects over 95% of the population worldwide. In the present study, the whole transcriptome microarray data were generated from peripheral blood mononuclear cells from Chinese children with acute infectious mononucleosis (AIM) and chronic active EBV infection (CAEBV) that were also compared with a publicly available microarray dataset from a study of American college students with AIM. Our study characterized for the first time a broad spectrum of molecular signatures in AIM and CAEBV. The key findings from the transcriptome profiling were validated with qPCR and flow cytometry assays. The most important finding in our study is the discovery of predominant γδ TCR expression and γδ T cell expansion in AIM. This finding, in combination with the striking up-regulation of CD3, CD8 and CD94, suggests that CD8+ T cells and CD94+ NK cells may play a major role in AIM. Moreover, the unique up-regulation of CD64A/B and its significant correlation with the monocyte marker CD14 was observed in CAEBV and that implies an important role of monocytes in CAEBV. In conclusion, our study reveals major cell types (particularly γδ T cells) in the host cellular immune response against AIM and CAEBV.

Highlights

  • Epstein–Barr virus (EBV), known as human herpesvirus-4, is one of the most important human pathogens worldwide

  • In Zhang et al.[11], Japanese children with EBV infections were studied and they identified a molecular signature from six SNK/T cell lines that were isolated from three patients with nasal natural killer (NK)/T-cell lymphoma and from the peripheral blood of three patients with chronic active EBV infection (CAEBV)

  • 12 acute infectious mononucleosis (AIM), 4 CAEBV and 14 healthy control subjects were used in the Quantitative PCR assay (qPCR) assays, and 28 AIM and 35 healthy control subjects were used in the flow cytometry assays

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Summary

Introduction

Epstein–Barr virus (EBV), known as human herpesvirus-4, is one of the most important human pathogens worldwide. Greenough et al analyzed gene expression of sorted CD8+ T cells from 10 American college students with AIM They reported a 28-gene molecular signature that correlated with CD8+ T cell expansion[14]. While these microarray profiling studies identified important molecular signatures and key genes associated with EBV infection, they have utilized sorted cells, cell lines, or microarray platforms with limited coverage of transcriptome, or they have been limited to specific populations with either AIM or CAEBV but not both in a single study. We evaluated the similarities and differences in expression of major immune molecules between the present study and a publicly available gene expression dataset from a study of American college students with AIM13. Our study will expand our understanding of the immunopathology of EBV infection and will serve as the basis for further exploration towards the development of diagnostic and therapeutic strategies for the EBV infection

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