scholarly journals Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis.

1981 ◽  
Vol 153 (2) ◽  
pp. 235-244 ◽  
Author(s):  
J E Robinson ◽  
D Smith ◽  
J Niederman

During the acute phase (1 wk of symptoms or less) of infectious mononucleosis (IM), 70--80% of circulating Epstein-Barr virus nuclear antigen (EBNA)-positive cells have differentiated toward plasma cells. Thus the characteristics of the infected cells in the majority of IM patients during early disease are indistinguishable from EBNA-positive tumor cells of a previously reported child who developed lymphoma during IM. IgA and IgG were the most frequent and IgM the least frequent immunoglobulin isotypes detected in EBNA-positive cells. In acute disease EBNA was present in 5.5--20% of T cell-depleted blood lymphocytes but in the 2nd or 3rd wk of illness the number of EBNA-positive cells sharply decreased to 0.4--1.4%. At the same time the fraction of antigen-positive cells containing cytoplasmic immunoglobulins also diminished, suggesting either that differentiation of infected cells was altered during the disease or that nondifferentiated antigen-positive cells had a survival advantage. Both the high proportion of plasmacytic EBNA-positive cells seen during acute disease and the apparent loss of differentiation by these cells later in disease may be regulated by host immunologic factors. Immunoglobulin-producing EBNA-positive cells may be the source of heterophile antibodies and other seemingly inappropriate antibodies usually found in serum during IM; however, increased numbers of noninfected plasma cells were present in some patients and may also be a potential source of these unusual antibodies.

1989 ◽  
Vol 20 (8) ◽  
pp. 796-799 ◽  
Author(s):  
G. Niedobitek ◽  
S. Hamilton-Dutoit ◽  
H. Herbst ◽  
T. Finn ◽  
M. Vetner ◽  
...  

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 744-750 ◽  
Author(s):  
I Anagnostopoulos ◽  
M Hummel ◽  
C Kreschel ◽  
H Stein

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.


2012 ◽  
Vol 84 (10) ◽  
pp. 1697-1697
Author(s):  
Mario Alejandro Lorenzetti ◽  
Marina Inés Gutiérrez ◽  
Jaime Altcheh ◽  
Guillermo Moscatelli ◽  
Samanta Moroni ◽  
...  

PEDIATRICS ◽  
1985 ◽  
Vol 75 (6) ◽  
pp. 1011-1019 ◽  
Author(s):  
Ciro Valent Sumaya ◽  
Yasmin Ench

An investigation was performed to address the need to establish the rate of positive heterophil antibody responses, oropharyngeal isolation of Epstein-Barr virus (EBV), and the evolving pattern of EBV-specific antibody responses among children with documented EBV-infectious mononucleosis. Findings showed that the rate of heterophil antibody responses appeared to increase progressively with advancing age from infancy up to 4 years, after which the rates approached values similar to that reported in young adult patients. The rapid slide test detected a heterophil antibody response as frequently as the Paul-Bunnell-Davidsohn horse cell test, except in children less than 4 years old. The decreased sensitivity found with the rapid slide test in the very young was associated with their less intense heterophil response. The younger group of children also developed a lower acute mean titer and, as a result, a decreased persistence of immunoglobulin M antibody to EBV-capsid antigen, whereas they had more frequent responses to EBV-early antigen directed to restricted component than both the older subjects and adults reported elsewhere. Antibodies to EBV-nuclear antigen, characteristically a late-onset antibody, tended to develop earlier than noted in adult patients. In contrast, the prevalence and continued excretion of EBV from oropharyngeal secretions was similar to that reported in adult patients. It is speculated that these age-related differences in host responses are associated with the ontogeny of the immunologic system.


PEDIATRICS ◽  
1976 ◽  
Vol 58 (6) ◽  
pp. 877-880
Author(s):  
Beverly J. Lange ◽  
Peter H. Berman ◽  
Joseph Bender ◽  
Werner Henle ◽  
John F. Hewetson

Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection.


2008 ◽  
Vol 89 (4) ◽  
pp. 866-877 ◽  
Author(s):  
Paul Young ◽  
Emma Anderton ◽  
Kostas Paschos ◽  
Rob White ◽  
Martin J. Allday

Viral nuclear oncoproteins EBNA3A and EBNA3C are essential for the efficient immortalization of B cells by Epstein–Barr virus (EBV) in vitro and it is assumed that they play an essential role in viral persistence in the human host. In order to identify cellular genes regulated by EBNA3A expression, cDNA encoding EBNA3A was incorporated into a recombinant adenoviral vector. Microarray analysis of human diploid fibroblasts infected with either adenovirus EBNA3A or an empty control adenovirus consistently showed an EBNA3A-specific induction of mRNA corresponding to the chaperones Hsp70 and Hsp70B/B′ and co-chaperones Bag3 and DNAJA1/Hsp40. Analysis of infected fibroblasts by real-time quantitative RT-PCR and Western blotting confirmed that EBNA3A, but not EBNA3C, induced expression of Hsp70, Hsp70B/B′, Bag3 and DNAJA1/Hsp40. This was also confirmed in a stable, inducible expression system. EBNA3A activated transcription from the Hsp70B promoter, but not multimerized heat-shock elements in transient transfection assays, consistent with specific chaperone and co-chaperone upregulation. Co-immunoprecipitation experiments suggest that EBNA3A can form a complex with the chaperone/co-chaperone proteins in both adenovirus-infected cells and EBV-immortalized lymphoblastoid cell lines. Consistent with this, induction of EBNA3A resulted in redistribution of Hsp70 from the cytoplasm to the nucleus. EBNA3A therefore specifically induces (and then interacts with) all of the factors necessary for an active Hsp70 chaperone complex.


2014 ◽  
Vol 42 (15) ◽  
pp. 9700-9716 ◽  
Author(s):  
Quentin Bazot ◽  
Thibaut Deschamps ◽  
Lionel Tafforeau ◽  
Maha Siouda ◽  
Pascal Leblanc ◽  
...  

AbstractThe Epstein–Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1.


Sign in / Sign up

Export Citation Format

Share Document