Modification of EBV-Associated Pathologies and Immune Control by Coinfections

Münz, Christian

doi:10.3389/fonc.2021.756480

Cited by 6 publications

(7 citation statements)

References 100 publications

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“…Despite this limitation, we are confident about the robustness of the study design, which allowed us to demonstrate for the first time that antibody levels to different P. vivax antigens were significantly lower in subjects with persistent EBV "DNAmia". As the main host cell of the EBV is the human B cell (reviewed by [67]), ongoing experiments are in progress to evaluate on the role of a persistent detection of EBV-DNA in the long-term P. vivax-specific B cell response. In this proof of concept study, we provide evidence that a persistent detection of EBV is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) in peripheral blood of an adult P. vivax semi-immune population may impact the long-term malaria immune response to major malaria vaccine candidates.…”

Section: Discussionmentioning

confidence: 99%

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

Dias

Guimarães

Barcelos

et al. 2022

Preprint

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Background: The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt's Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. Methodology/Principal Findings: The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed adults living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersV DNA, n=27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegV DNA, n=29). During the follow-up period, the serological detection of EBV antibodies to lytic/latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersV DNA > NegV DNA ). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersV DNA group showed low levels of antibodies as compared with NegV DNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. Conclusions/Significance: In a proof-of-concept study we provide evidence that a persistent detection of EBV DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.

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Section: Discussionmentioning

confidence: 99%

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

Dias

Guimarães

Barcelos

et al. 2022

Preprint

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“…Notwithstanding these limitations, we are confident about the robustness of the study design, which allowed us to demonstrate for the first time that antibody levels to different P. vivax antigens were significantly lower in subjects with persistent EBV “DNAmia”. As the main host cell of the EBV is the human B cell (reviewed by [ 80 ]), ongoing experiments are in progress to evaluate on the role of a persistent detection of EBV-DNA in the long-term P . vivax -specific B cell response.…”

Section: Discussionmentioning

confidence: 99%

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

et al. 2022

View full text Add to dashboard Cite

Background The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt’s Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. Methodology/Principal findings The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. Conclusions/Significance In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.

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“…Moreover, in patients with chronic HIV infection, which results in CD4 T-cell loss and reduced anti-viral function of CD8 T and NK cells, uncontrolled proliferation of EBV-infected lymphocytes may occur; accordingly, most HIV-associated LPDs display a plasma cell phenotype and are linked to EBV infection [ 33 ]. Moreover, simultaneous infection with Plasmodium falciparum or Kaposi sarcoma-associated herpesvirus (KSHV) results in higher EBV-positivity of LPDs in coinfected patients, which has been attributed to the capacity of the coinfecting pathogens to reduce the anti-EBV function of T and NK cells and to directly stimulate the pathogenic potential of EBV [ 34 ]. Of great clinical importance, individuals affected with various IEI can develop severe or even fatal EBV-induced diseases, an area of extensive investigation that has produced considerable information on the aspects of immunity that crucially control EBV infection.…”

Section: Complex Ebv Infection In the Context Of Immunodeficiencymentioning

confidence: 99%

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

Desimio

Covino

Rivalta

et al. 2023

Cancers

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The Epstein–Barr virus (EBV) is a ubiquitous herpesvirus most often transmitted during infancy and infecting the vast majority of human beings. Usually, EBV infection is nearly asymptomatic and results in life-long persistency of the virus in a latent state under the control of the host immune system. Yet EBV can cause an acute infectious mononucleosis (IM), particularly in adolescents, and is associated with several malignancies and severe diseases that pose a serious threat to individuals with specific inborn error of immunity (IEI). While there is a general consensus on the requirement for functional CD8 T cells to control EBV infection, the role of the natural killer (NK) cells of the innate arm of immunity is more enigmatic. Here we provide an overview of the interaction between EBV and NK cells in the immunocompetent host as well as in the context of primary and secondary immunodeficiencies. Moreover, we report in vitro data on the mechanisms that regulate the capacity of NK cells to recognize and kill EBV-infected cell targets and discuss the potential of recently optimized NK cell-based immunotherapies for the treatment of EBV-associated diseases.

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Modification of EBV-Associated Pathologies and Immune Control by Coinfections

Cited by 6 publications

References 100 publications

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response

The Role of NK Cells in EBV Infection and Related Diseases: Current Understanding and Hints for Novel Therapies

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