Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus

Abstract

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

Prevalence of Epstein–Barr virus in tonsils and adenoids of United Arab Emirates nationals

“…However, there is now increasing evidence pointing to B lymphocytes as the likely site of persistent EBV infection, and also as the possible target of primary EBV infection [34]. Several studies have demonstrated EBV replication within the upper epithelial cell layers in oral hairy leukoplakia and are not accompanied by detectable latent infection of basal epithelial cells [35,36]. Thus, these results do not support the idea that EBV persists in epithelial cells.…”

Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein‐Barr Virus Infectious Mononucleosis

“…This is important because evidence supports EBV production in salivary glands, oropharyngeal epithelial cells, and B cells in the oropharynx. [16][17][18][19][20] Person-to-person transmission of EBV is believed to occur through exchange of infected oral fluids and cells. If EBV replication in the oral cavity is inhibited by antiviral therapy, then transmission of infectious virus may be reduced.…”

Current research on chronic active Epstein–Barr virus infection in Japan

“…38 Given that EBV-positive T or NK cells have been occasionally found in the tonsil and peripheral blood of IM patients, ectopic EBV infection in T or NK cells does not necessarily lead to the development of CAEBV. [39][40][41] Although EBV-infected T and NK cells in CAEBV patients and cell lines derived from them do not express the most immunodominant EBNA3 and EBNA2, they express EBNA1, latent membrane protein 1 (LMP1) and LMP2 (the latency II type EBV gene expression) that are frequently recognized by EBV-specific CTL. 3,[42][43][44][45] Hosts with normal immune functions are thus expected to have the capacity to recognize EBV-infected T and NK cells.…”