B-cell polyclonal activation and Epstein-Barr viral abortive lytic cycle are two key features in acute infectious mononucleosis

J Clin Virol. 2011 Sep;52(1):33-7. doi: 10.1016/j.jcv.2011.05.023.

Abstract

Background: Acute infectious mononucleosis (AIM) is generally associated with a large EBV B cell reservoir cells and an intense B-cell polyclonal activation whereas the number of quiescent EBV-infected memory B cells in chronically EBV-infected healthy controls is very low.

Objectives: To evaluate the extent and functionality of ex vivo B-cell polyclonal activation, quantify the EBV DNA integrated in B cells, enumerate the functional EBV DNA reservoir in B cells and circulating B cells spontaneously secreting EBV antigens in AIM.

Study design: Circulating B cells and B cells differentiating into plamablasts and plasma cells, early (BZLF1)- and late viral antigen (gp350)-secreting-cells (SCs) were enumerated in six AIM patients and seven healthy EBV carriers.

Results: In vitro B-cell polyclonal activation induced 8000-24,000 BZLF1- and 1000-3000gp350-SCs/10(6) B cells, respectively. These data suggest that only 11.1-19.5% of cells expressing BZLF1 synthesized gp350 and so completed the EBV-lytic cycle. Furthermore, circulating spontaneous BZLF1- and gp350-SCs that reflect ongoing viral replication were rare (20-120 and 10-30/10(6) B cells, respectively), and their low numbers contrasted with the high levels of circulating plasma cells (1.1-10.2% of CD19(+) B cells).

Conclusion: The in vivo terminal-B-cell differentiation into plasma cells could unmask EBV B-cell reservoir to specific cytotoxic T-cell response and combined with a predominant abortive functional-EBV-reservoir, strongly contribute to rapid decay of cellular EBV reservoir in AIM.

MeSH terms

  • Acute Disease
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Infectious Mononucleosis / diagnosis
  • Infectious Mononucleosis / immunology*
  • Infectious Mononucleosis / pathology
  • Lymphocyte Activation / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Trans-Activators / analysis
  • Trans-Activators / biosynthesis
  • Trans-Activators / metabolism
  • Viral Proteins / analysis
  • Viral Proteins / biosynthesis
  • Viral Proteins / metabolism
  • alpha-Macroglobulins / immunology

Substances

  • Antigens, Viral
  • BZLF1 protein, Herpesvirus 4, Human
  • Epstein-Barr Virus Nuclear Antigens
  • Trans-Activators
  • Viral Proteins
  • alpha-Macroglobulins
  • polyclonal B cell activator