Animal models of Epstein Barr virus infection

Gujer, Cornelia; Chatterjee, Bithi; Landtwing, Vanessa; Raykova, Ana; McHugh, Donal; Münz, Christian

doi:10.1016/j.coviro.2015.03.014

Cited by 24 publications

(20 citation statements)

References 62 publications

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“…If these transformed cells are not killed, LPD and cancer can develop. EBV-induced LPD and tumors develop in both the Hu-PBL-SCID and Hu-SRC-SCID models (44, 45). …”

Section: Infectious Disease In Humanized Micementioning

confidence: 99%

Humanized Mouse Models of Clinical Disease

Walsh

Kenney

Jangalwe

et al. 2017

Annu. Rev. Pathol. Mech. Dis.

443

384

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Immunodeficient mice engrafted with functional human cells and tissues, i.e., “humanized mice”, have become increasingly important as small pre-clinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rgnull) in the early 2000’s, investigators have been able to engraft murine recipients with human hematopoietic stem cells that develop into functional human immune systems. These mice can also be engrafted with human tissues such as islets, liver, skin, and most solid and hematologic cancers. Humanized mice are permitting significant progress in studies of human infectious disease, cancer, regenerative medicine, graft versus host disease, allergies, and immunity. Ultimately, use of humanized mice may lead to the implementation of truly “personalized” medicine in the clinic. This review discusses recent progress in the development and use of humanized mice, and highlights their utility for the study of human diseases.

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“…If these transformed cells are not killed, LPD and cancer can develop. EBV-induced LPD and tumors develop in both the Hu-PBL-SCID and Hu-SRC-SCID models (44, 45). …”

Section: Infectious Disease In Humanized Micementioning

confidence: 99%

Humanized Mouse Models of Clinical Disease

Walsh

Kenney

Jangalwe

et al. 2017

Annu. Rev. Pathol. Mech. Dis.

443

384

View full text Add to dashboard Cite

show abstract

“…There is currently no vaccine or effective treatment for AIM or other EBV related diseases. Because EBV infection is limited to primates, there are no small animal models of infection except humanized mice [ 5 ]. Neither humanized mice nor mice infected with the related gamma herpesvirus MHV68 exhibit true AIM.…”

Section: Introductionmentioning

confidence: 99%

The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events

et al. 2015

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Epstein-Barr virus (EBV) is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV’s lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset–coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in concert with viral genomes increasing in the blood and oral cavity, possibly due to a systemic type I interferon response. This study provides the first description of events during the incubation period of natural EBV infection in humans and definitive data upon which to formulate theories of viral control and disease pathogenesis.

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“…Using the EBER mutant EBV strains, we tested whether EBERs affect establishment of EBV infection in NSG mice with a humanized hematopoietic system ( 11 ). In three separate experiments involving a total of 44 correctly reconstituted mice, there was no significant difference between the frequencies of infection detected in the blood or in the spleen with deletion of either or both EBER genes from the virus genome.…”

Section: Textmentioning

confidence: 99%

Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice

Gregorovic

Boulden

Bosshard

et al. 2015

J Virol

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Functions of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were tested in lymphoblastoid cell lines containing EBER mutants of EBV. Binding of EBER1 to ribosomal protein L22 (RPL22) was confirmed. Deletion of EBER1 or EBER2 correlated with increased levels of cytoplasmic EBV LMP2 RNA and with small effects on specific cellular microRNA (miRNA) levels, but protein levels of LMP1 and LMP2A were not affected. Wild-type EBV and EBER deletion EBV had approximately equal abilities to infect immunodeficient mice reconstituted with a human hematopoietic system.

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Animal models of Epstein Barr virus infection

Cited by 24 publications

References 62 publications

Humanized Mouse Models of Clinical Disease

Humanized Mouse Models of Clinical Disease

The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events

Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice

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