Epstein-Barr virus: the impact of scientific advances on clinical practice

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 862-869 ◽  
Author(s):  
Hilary Williams ◽  
Dorothy H. Crawford

AbstractEpstein-Barr virus (EBV) is a tumorigenic herpes virus that infects and persists in B lymphocytes in the majority of humans, generally without causing disease. However, in a few individuals the virus is associated with significant pathology, particularly benign and malignant lymphoproliferations. Recently acquired knowledge on the mechanisms of EBV persistence, immune control of primary and persistent infection, and disease pathogenesis is now being translated into the clinic with novel methods of diagnosis, prevention and treatment contributing to improved patient care. This review concentrates on these recent advances in the field of hematology/oncology.

2021 ◽  
Vol 49 (18) ◽  
pp. 10657-10676
Author(s):  
Evelyne Manet ◽  
Hélène Polvèche ◽  
Fabrice Mure ◽  
Paulina Mrozek-Gorska ◽  
Florian Roisné-Hamelin ◽  
...  

Abstract Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides—besides transcription—an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP—together with the RBM4 splicing factor—in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.


2003 ◽  
Vol 198 (11) ◽  
pp. 1653-1663 ◽  
Author(s):  
Kara Bickham ◽  
Kiera Goodman ◽  
Casper Paludan ◽  
Sarah Nikiforow ◽  
Ming Li Tsang ◽  
...  

The initiation of cell-mediated immunity to Epstein-Barr virus (EBV) has been analyzed with cells from EBV-seronegative blood donors in culture. The addition of dendritic cells (DCs) is essential to prime naive T cells that recognize EBV-latent antigens in enzyme-linked immunospot assays for interferon γ secretion and eradicate transformed B cells in regression assays. In contrast, DCs are not required to control the outgrowth of EBV-transformed B lymphocytes from seropositive donors. Enriched CD4+ and CD8+ T cells mediate regression of EBV-transformed cells in seronegative and seropositive donors, but the kinetics of T-dependent regression occurs with much greater speed with seropositives. EBV infection of DCs cannot be detected by reverse transcription–polymerase chain reaction with primers specific for mRNA for the EBNA1 U and K exons. Instead, DCs capture B cell debris and generate T cells specific for EBV latency antigens. We suggest that the cross-presentation of EBV-latent antigens from infected B cells by DCs is required for the initiation of EBV-specific immune control in vivo and that future EBV vaccine strategies should target viral antigens to DCs.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 285
Author(s):  
Xinle Cui ◽  
Zhouhong Cao ◽  
Yuriko Ishikawa ◽  
Sara Cui ◽  
Ken-Ichi Imadome ◽  
...  

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.


1994 ◽  
Vol 269 (29) ◽  
pp. 18743-18746 ◽  
Author(s):  
F.E. Maly ◽  
L.A. Quilliam ◽  
O. Dorseuil ◽  
C.J. Der ◽  
G.M. Bokoch

2014 ◽  
Vol 58 (2-3) ◽  
pp. 268-276 ◽  
Author(s):  
Olivia L. Hatton ◽  
Aleishia Harris-Arnold ◽  
Steven Schaffert ◽  
Sheri M. Krams ◽  
Olivia M. Martinez

Author(s):  
David Liebowitz ◽  
Elliott Kieff ◽  
Jeffery Sample ◽  
Mark Birkenbach ◽  
Fred Wang

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