Human Natural Killer Cells Prevent Infectious Mononucleosis Features by Targeting Lytic Epstein-Barr Virus Infection

Chijioke, Obinna; Müller, Anne; Feederle, Regina; Barros, Mário Henrique M.; Krieg, Carsten; Emmel, Vanessa Erichsen; Marcenaro, Emanuela; Leung, Carol S.; Antsiferova, Olga; Landtwing, Vanessa; Bossart, Walter; Moretta, Alessandro; Hassan, Rocı́o; Boyman, Onur; Niedobitek, Gerald; Delecluse, Henri Jacques; Capaul, Riccarda; Münz, Christian

doi:10.1016/j.celrep.2013.11.041

“…Frequency of EBV-reactive CD8 effector cells has been shown to be reduced in MS [25], deficiency of NK cells has been associated with reduced control of EBV [26], and EBV infection may be a prerequisite for MS [27]. Antibodies to the EBV protein EBNA-1 have been shown to increase with EBV activation and are used as a proxy measurement of EBV activity [28].…”

Section: Is Epstein Barr Virus Ebna-1 Titre Associated With the Et Phmentioning

confidence: 99%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

¹

,

Gatt

²

,

Fewings

³

et al. 2016

Clinical Immunology

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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p<10 -4 ) and high heritability (h 2 =0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were underrepresented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

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“…Both latent and lytic EBV antigen expression can be observed in infected HIS mice (Strowig et al, 2009;Chijioke et al, 2013;Tsai et al, 2013). Depending on the dose of EBV, it is possible to generate asymptomatic persistent infection or acute infectious mononucleosis-like symptoms, as well as lymphoproliferative disease in HIS mice (Yajima et al, 2008).…”

Section: Programs Of Ebv Infection In His Micementioning

confidence: 99%

“…This could indicate that a low level of T cell interaction with B cells in HIS mice allows for the access of lower EBV latency programs. Nevertheless, persistent infection with EBV in HIS mice does not depend on lytic replication, because EBV lacking BZLF1, the immediate early transactivator of lytic replication, can still establish infection in HIS mice (Ma et al, 2011;Chijioke et al, 2013).…”

Section: Programs Of Ebv Infection In His Micementioning

confidence: 99%

Animal models of Epstein Barr virus infection

Chatterjee

¹

,

Leung

²

,

Münz

³

2014

Journal of Immunological Methods

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Epstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. AbstractEpstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50 years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. Chatterjee et al. 3

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“…In these rare, lytically EBV replicating cells however, both early and late lytic antigen expression can be found (Chijioke et al, 2013). Accordingly, both cellassociated and plasma viral DNA loads can be detected in EBV infected HIS mice (Chijioke et al, 2013). However, it remains unclear how much of the plasma viral DNA load is infectious or 7 whether it could merely be DNA released from dying infected cells.…”

Section: Programs Of Ebv Infection In His Micementioning

confidence: 99%

“…In addition to T cells, NK cells have been also depleted in HIS mice. The NKp46 specific antibody BAB281 (mIgG1) was applied on 3 consecutive days with an intraperitoneal dose of 100 g per mouse (Chijioke et al, 2013).…”

Section: Antibody Depletion Of Ebv Specific Immune Controlmentioning

confidence: 99%

Animal models of Epstein Barr virus infection

Gujer

¹

,

Chatterjee

²

,

Landtwing

³

et al. 2015

Current Opinion in Virology

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Epstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. AbstractEpstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50 years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. Chatterjee et al. 3

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Human Natural Killer Cells Prevent Infectious Mononucleosis Features by Targeting Lytic Epstein-Barr Virus Infection

Cited by 189 publications

References 45 publications

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Animal models of Epstein Barr virus infection

Animal models of Epstein Barr virus infection

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