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Published on: March 30, 2018
Epstein Barr Virus (EBV) Latent Membrane Protein 1 (LMP-1) Regulates Functional Markers in Intermediate and
Agustina Moyano1, Ana Colado2, María Eugenia Amarillo1
1Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires C1425EFD, Argentina.
Insights
Epstein-Barr virus (EBV) infection involves intermediate (I) and non-classical (NC) monocytes. The EBV oncoprotein LMP-1 influences regulatory protein expression in these monocytes, impacting immune response.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Epstein-Barr virus (EBV) infects over 90% of humans, with innate immunity crucial in pediatric primary infection.
- Monocytes, including classical, intermediate (I), and non-classical (NC) subpopulations, play diverse roles in immune modulation.
- The specific involvement of monocyte subpopulations in EBV infection remains largely unexplored.
Purpose of the Study:
- To investigate the role of distinct monocyte subpopulations in Epstein-Barr virus (EBV) primary infection, healthy carriers, and reactivation.
- To explore the correlation between EBV infection status and the expression of specific cell surface markers on monocytes.
- To determine the influence of the EBV oncoprotein LMP-1 on monocyte subpopulations.
Main Methods:
- Analysis of peripheral blood and tonsil biopsies from EBV primary infected (PI), healthy carriers (HC), and reactivation (R) patients.
- Differentiation and characterization of monocyte subpopulations (classical, intermediate, non-classical) based on membrane protein expression.
- Correlation analysis of immune cell markers (CD163, PD-L1) and the EBV latent protein LMP-1.
Main Results:
- Classical monocytes were predominant across all EBV infection statuses.
- Significant positive correlations were observed between tonsillar CD163 and CD163 expression in non-classical (NC) monocytes in healthy carriers.
- PD-L1 expression in tonsillar cells positively correlated with PD-L1 on NC monocytes, and LMP-1 showed a positive correlation with PD-L1, CD163, and CD206 in the NC subpopulation.
Conclusions:
- Intermediate (I) and non-classical (NC) monocytes exhibit a predominant response during Epstein-Barr virus (EBV) infection.
- The EBV oncoprotein LMP-1 may regulate the expression of key proteins, including PD-L1 and CD163, on I and NC monocytes.
- These findings highlight the critical role of specific monocyte subsets in the immune response to EBV.
Abstract:
Background: The Epstein-Barr virus (EBV) infects more than 90 percent of the human population. In pediatric patients, the innate immune response against EBV primary infection plays a key role. Monocytes and macrophages can have distinct functions depending on the microenvironment surrounding them. At least three monocyte subpopulations can be differentiated depending on membrane protein expression: classical (C, CD14++CD16-), intermediate (I, CD14++CD16+), and non-classical (NC, CD14+CD16++). They also modulate T and B lymphocyte activation/inhibition through the expression of costimulatory molecules such as CD80, CD86, and PD-L1. Yet, little is known about monocytes' role in EBV infection. Methods: Peripheral blood and tonsil biopsies of EBV primary infected (PI) patients, healthy carriers (HCs), and patients undergoing reactivation (R) were studied. Results: Classical monocytes prevailed in all infectious statuses. Tonsillar CD163 positively correlated with CD163 expression in NC monocytes in HCs. PD-L1+ cells in the tonsil positively correlated with PD-L1 expression in NC monocytes. LMP-1 viral latent protein presented a positive correlation with PD-L1, CD163, and CD206 expression in the NC subpopulation. Conclusions: Our results evidence the predominant role of I and NC monocytes' response against EBV infection. Furthermore, the viral oncoprotein LMP-1 could be involved in the expression of regulatory proteins in I and NC monocytes.
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