scholarly journals Modification of EBV-Associated Pathologies and Immune Control by Coinfections

2021 ◽  
Vol 11 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Adult Population ◽  
Kaposi Sarcoma ◽  
Human Immune System ◽  
Immune Control ◽  
Barr Virus ◽  
Human B Cells ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Underlying Mechanisms

The oncogenic Epstein–Barr virus (EBV) persistently infects more than 95% of the human adult population. Even so it can readily transform human B cells after infection in vitro, it only rarely causes tumors in patients. A substantial proportion of the 1% of all human cancers that are associated with EBV occurs during coinfections, including those with the malaria parasite Plasmodium falciparum, the human immunodeficiency virus (HIV), and the also oncogenic and closely EBV-related Kaposi sarcoma-associated herpesvirus (KSHV). In this review, I will discuss how these infections interact with EBV, modify its immune control, and shape its tumorigenesis. The underlying mechanisms reveal new aspects of EBV-associated pathologies and point toward treatment possibilities for their prevention by the human immune system.

scholarly journals Modification of EBV Associated Lymphomagenesis and Its Immune Control by Co-Infections and Genetics in Humanized Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Schuhmachers ◽  
Christian Münz
Keyword(s):  
Adult Population ◽  
Human Tumor ◽  
Kaposi Sarcoma ◽  
Humanized Mice ◽  
Immune Control ◽  
Barr Virus ◽  
Human B Cells ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Potent Growth

Epstein Barr virus (EBV) is one of the most successful pathogens in humans with more than 95% of the human adult population persistently infected. EBV infects only humans and threatens these with its potent growth transforming ability that readily allows for immortalization of human B cells in culture. Accordingly, it is also found in around 1-2% of human tumors, primarily lymphomas and epithelial cell carcinomas. Fortunately, however, our immune system has learned to control this most transforming human tumor virus in most EBV carriers, and it requires modification of EBV associated lymphomagenesis and its immune control by either co-infections, such as malaria, Kaposi sarcoma associated herpesvirus (KSHV) and human immunodeficiency virus (HIV), or genetic predispositions for EBV positive tumors to emerge. Some of these can be modelled in humanized mice that, therefore, provide a valuable platform to test curative immunotherapies and prophylactic vaccines against these EBV associated pathologies.

scholarly journals Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 217 ◽  
Author(s):  
Christian Münz
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Adult Population ◽  
Humanized Mice ◽  
Cytotoxic Lymphocytes ◽  
Human Immune System ◽  
Immune Control ◽  
Cytotoxic Lymphocyte ◽  
Barr Virus ◽  
Epstein Barr

Mice with reconstituted human immune system components (humanized mice) offer the unique opportunity to test vaccines preclinically in the context of vaccine adjuvant sensing by human antigen presenting cells and priming of human cytotoxic lymphocyte populations. These features are particularly attractive for immune control of the Epstein–Barr virus (EBV), which represents the most potent growth-transforming pathogen in man and exclusively relies on cytotoxic lymphocytes for its asymptomatic persistence in the vast majority of healthy virus carriers. This immune control is particularly impressive because EBV infects more than 95% of the human adult population and persists without pathology for more than 50 years in most of them. This review will discuss the pathologies that EBV elicits in humanized mice, which immune responses control it in this model, as well as which passive and active vaccination schemes with adoptive T cell transfer and with virus-like particles or individual antigens, respectively, have been explored in this model so far. EBV-specific CD8+ T cell priming in humanized mice could provide crucial insights into how cytotoxic lymphocytes against other viruses and tumors might be elicited by vaccination in humans.

scholarly journals The Role of Dendritic Cells in Immune Control and Vaccination against γ-Herpesviruses

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1125 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Kaposi Sarcoma ◽  
Immune Control ◽  
Barr Virus ◽  
Persistent Infections ◽  
Cell Responses ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Antigen Presenting ◽  
Adoptive Transfer Therapy

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they serve as paradigms of how near-perfect cell-mediated immune control can be initiated and maintained for decades. Interestingly, EBV especially quite efficiently avoids dendritic cell (DC) activation, and little evidence exists that these most potent antigen-presenting cells of the human body are involved in the priming of immune control against this tumor virus. However, DCs can be harnessed therapeutically to expand virus-specific T cells for adoptive transfer therapy of patients with virus-associated malignancies and are also currently explored for vaccinations. Unfortunately, despite 55 and 25 years of research on EBV and KSHV, respectively, the priming of their immune control that belongs to the most robust and durable immune responses in humans still remains unclear.

scholarly journals How Epstein-Barr Virus “Manipulates” The Tumoral Microenvironment in Hodgkin Lymphoma?

2019 ◽  
Vol 16 (2) ◽  
pp. 47-52
Author(s):  
Andrei Turbatu ◽  
Andrei Coliţă ◽  
Marilena Stoian ◽  
Ana-Maria Bordea ◽  
Mădălina Oprea ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Primary Infection ◽  
Epstein Barr Virus ◽  
Adult Population ◽  
In Vivo Models ◽  
Benign Condition ◽  
Barr Virus ◽  
Epstein Barr

AbstractThe Epstein-Barr virus (EBV) is a gamma-herpesvirus that colonizes the B-cell system of its human host, allowing it to persist asymptomatically in the majority of the world’s adult population. In most people primary infection goes unnoticed, whereas in a minority of individuals, primary infection results in infectious mononucleosis (IM), a benign condition that almost always resolves after several weeks or months. However, EBV is also causally linked with a number of malignancies, including B-cell lymphomas, such as classical Hodgkin lymphoma (cHL).A proportion of patients with cHL harbor EBV within their tumor cells. Emerging evidence suggests that while EBV is able to subvert cellular processes to promote the growth and survival of HRS cells or their progenitors, mutations in key cell signalization pathways are probably required to do this when EBV is absent. The challenge is to unravel exactly how EBV and its latent genes contribute to the pathogenesis of cHL particularly with respect to how the virus co-operates with cellular genetic and epigenetic changes to drive transformation. It is hoped that the development of better in vitro and in vivo models of disease will reveal more fundamental aspects of EBV’s role in Hodgkin lymphoma pathogenesis and pave the way for targeted therapies for patients with EBV-positive cHL.

scholarly journals Mechanisms of B-Cell Oncogenesis Induced by Epstein-Barr Virus

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Abhik Saha ◽  
Erle S. Robertson
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Genetically Engineered ◽  
World Population ◽  
Barr Virus ◽  
Viral Particles ◽  
Epstein Barr ◽  
Underlying Mechanisms

ABSTRACTEpstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus which asymptomatically infects the majority of the world population. Under immunocompromised conditions, EBV can trigger human cancers of epithelial and lymphoid origin. The oncogenic potential of EBV is demonstrated byin vitroinfection and transformation of quiescent B cells into lymphoblastoid cell lines (LCLs). These cell lines, along with primary infection using genetically engineered viral particles coupled with recent technological advancements, have elucidated the underlying mechanisms of EBV-induced B-cell lymphomagenesis.

scholarly journals Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1231-1239 ◽  
Author(s):  
Cagan Gurer ◽  
Till Strowig ◽  
Fabienne Brilot ◽  
Maggi Pack ◽  
Christine Trumpfheller ◽  
...  
Keyword(s):  
T Cells ◽  
Epstein Barr Virus ◽  
Poly I:C ◽  
Nuclear Antigen ◽  
Human Immune System ◽  
Proliferating Cells ◽  
Mhc I ◽  
Barr Virus ◽  
Epstein Barr

Abstract Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8+ and CD4+ T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor, in the presence of the DC maturation stimulus poly(I:C), expanded EBNA1-specific CD4+ and CD8+ memory T cells, and these lymphocytes could control the outgrowth of autologous EBV-infected B cells in vitro. In addition, using a novel mouse model with reconstituted human immune system components, we demonstrated that vaccination with αDEC-205-EBNA1 antibodies primed EBNA1-specific IFN-γ–secreting T cells and also induced anti-EBNA1 antibodies in a subset of immunized mice. Because EBNA1 is the one EBV antigen that is expressed in all proliferating cells infected with this virus, our data suggest that DEC-205 targeting should be explored as a vaccination approach against symptomatic primary EBV infection and against EBV-associated malignancies.

scholarly journals Oncogenic Viral Prevalence in Invasive Vulvar Cancer Specimens From Human Immunodeficiency Virus–Positive and -Negative Women in Botswana

2014 ◽  
Vol 24 (4) ◽  
pp. 758-765 ◽  
Author(s):  
Martha Tesfalul ◽  
Kenneth Simbiri ◽  
Chikoti M. Wheat ◽  
Didintle Motsepe ◽  
Hayley Goldbach ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Kaposi Sarcoma ◽  
Oncogenic Viruses ◽  
Hiv Status ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Viral Testing ◽  
Epstein Barr

ObjectiveThe primary aim of this study was to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with human immunodeficiency virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world.MethodsA cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) viral testing were done for Epstein-Barr virus, human papillomavirus (HPV) strains, and Kaposi sarcoma herpesvirus, and PCR viral testing alone was done for John Cunningham virus.ResultsHuman papillomavirus prevalence by PCR was 100% (35/35) among tested samples. Human papillomavirus type 16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). Kaposi sarcoma herpesvirus prevalence by PCR had a significant association with HIV status (P = 0.013), but not by IHC (P = 0.650).ConclusionsThe high burden of HPV, specifically HPV16, in vulvar squamous cell cancer in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses Kaposi sarcoma herpesvirus and Epstein-Barr virus were also more prevalent in our study population, although their potential role in vulvar squamous cell cancer pathology is unclear.

scholarly journals Dendritic Cells Initiate Immune Control of Epstein-Barr Virus Transformation of B Lymphocytes In Vitro

2003 ◽  
Vol 198 (11) ◽  
pp. 1653-1663 ◽  
Author(s):  
Kara Bickham ◽  
Kiera Goodman ◽  
Casper Paludan ◽  
Sarah Nikiforow ◽  
Ming Li Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
Cell Mediated Immunity ◽  
Immune Control ◽  
Barr Virus ◽  
Epstein Barr

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.

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