T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice

Frank Heuts, Martin E. Rottenberg, D. Salamon, Eahsan Rasul, Monika Adori, George Klein, Eva Klein, Noemi Nagy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Human B cells, the main target of Epstein-Barr virus (EBV), can display several types of latent viral protein expression, denoted 0, I, IIa, IIb, or III. Of these, only type III expression induces proliferation of cells in vitro. These latency types are present at specific stages of infection and are also characteristic of different tumor types, but their generation is not fully understood. In this study, we analyzed the role of T cells in the regulation of EBV viral latency by using humanized NOD/SCID/IL2Rγ-/- mice. Several spleens presented macroscopic tumors 4 weeks after infection. Explanted spleen B cells from some of the EBV-infected mice proliferated in vitro, but this was usually lowered when cyclosporine was added to the cultures. This suggested that the in vitro growth of EBV-infected B cells required T cell help; thus, cells other than type III cells were also present in the spleens. Quantitative PCR analysis of promoter activities specific for the different EBV latency types confirmed that in addition to type III cells, type IIa and type I cells were present in the spleen. The relative usage of the viral promoter specific for I and IIa latency types (Q promoter) was higher in CD8+ cell-depleted mice, and it was absent from CD4+ cell-depleted mice. These results indicate that CD4+ T cells are necessary for the generation/maintenance of cells with latency I/IIa in the humanized mice. CD4+ T cells contributed to this process through their CD40L expression.

Original languageEnglish
Pages (from-to)3235-3245
Number of pages11
JournalJournal of Virology
Volume88
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Virus Latency
Human herpesvirus 4
Human Herpesvirus 4
T-lymphocytes
T-Lymphocytes
Phenotype
phenotype
mice
Infection
infection
spleen
Spleen
B-lymphocytes
cells
B-Lymphocytes
promoter regions
CD40 Ligand
neoplasms
cyclosporine
SCID Mice

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Heuts, F., Rottenberg, M. E., Salamon, D., Rasul, E., Adori, M., Klein, G., ... Nagy, N. (2014). T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice. Journal of Virology, 88(6), 3235-3245. https://doi.org/10.1128/JVI.02885-13

T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice. / Heuts, Frank; Rottenberg, Martin E.; Salamon, D.; Rasul, Eahsan; Adori, Monika; Klein, George; Klein, Eva; Nagy, Noemi.

In: Journal of Virology, Vol. 88, No. 6, 2014, p. 3235-3245.

Research output: Contribution to journalArticle

Heuts, F, Rottenberg, ME, Salamon, D, Rasul, E, Adori, M, Klein, G, Klein, E & Nagy, N 2014, 'T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice', Journal of Virology, vol. 88, no. 6, pp. 3235-3245. https://doi.org/10.1128/JVI.02885-13
Heuts, Frank ; Rottenberg, Martin E. ; Salamon, D. ; Rasul, Eahsan ; Adori, Monika ; Klein, George ; Klein, Eva ; Nagy, Noemi. / T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice. In: Journal of Virology. 2014 ; Vol. 88, No. 6. pp. 3235-3245.
@article{799d6ed0dd62499e99e3c6c1e23b10ce,
title = "T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice",
abstract = "Human B cells, the main target of Epstein-Barr virus (EBV), can display several types of latent viral protein expression, denoted 0, I, IIa, IIb, or III. Of these, only type III expression induces proliferation of cells in vitro. These latency types are present at specific stages of infection and are also characteristic of different tumor types, but their generation is not fully understood. In this study, we analyzed the role of T cells in the regulation of EBV viral latency by using humanized NOD/SCID/IL2Rγ-/- mice. Several spleens presented macroscopic tumors 4 weeks after infection. Explanted spleen B cells from some of the EBV-infected mice proliferated in vitro, but this was usually lowered when cyclosporine was added to the cultures. This suggested that the in vitro growth of EBV-infected B cells required T cell help; thus, cells other than type III cells were also present in the spleens. Quantitative PCR analysis of promoter activities specific for the different EBV latency types confirmed that in addition to type III cells, type IIa and type I cells were present in the spleen. The relative usage of the viral promoter specific for I and IIa latency types (Q promoter) was higher in CD8+ cell-depleted mice, and it was absent from CD4+ cell-depleted mice. These results indicate that CD4+ T cells are necessary for the generation/maintenance of cells with latency I/IIa in the humanized mice. CD4+ T cells contributed to this process through their CD40L expression.",
author = "Frank Heuts and Rottenberg, {Martin E.} and D. Salamon and Eahsan Rasul and Monika Adori and George Klein and Eva Klein and Noemi Nagy",
year = "2014",
doi = "10.1128/JVI.02885-13",
language = "English",
volume = "88",
pages = "3235--3245",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice

AU - Heuts, Frank

AU - Rottenberg, Martin E.

AU - Salamon, D.

AU - Rasul, Eahsan

AU - Adori, Monika

AU - Klein, George

AU - Klein, Eva

AU - Nagy, Noemi

PY - 2014

Y1 - 2014

N2 - Human B cells, the main target of Epstein-Barr virus (EBV), can display several types of latent viral protein expression, denoted 0, I, IIa, IIb, or III. Of these, only type III expression induces proliferation of cells in vitro. These latency types are present at specific stages of infection and are also characteristic of different tumor types, but their generation is not fully understood. In this study, we analyzed the role of T cells in the regulation of EBV viral latency by using humanized NOD/SCID/IL2Rγ-/- mice. Several spleens presented macroscopic tumors 4 weeks after infection. Explanted spleen B cells from some of the EBV-infected mice proliferated in vitro, but this was usually lowered when cyclosporine was added to the cultures. This suggested that the in vitro growth of EBV-infected B cells required T cell help; thus, cells other than type III cells were also present in the spleens. Quantitative PCR analysis of promoter activities specific for the different EBV latency types confirmed that in addition to type III cells, type IIa and type I cells were present in the spleen. The relative usage of the viral promoter specific for I and IIa latency types (Q promoter) was higher in CD8+ cell-depleted mice, and it was absent from CD4+ cell-depleted mice. These results indicate that CD4+ T cells are necessary for the generation/maintenance of cells with latency I/IIa in the humanized mice. CD4+ T cells contributed to this process through their CD40L expression.

AB - Human B cells, the main target of Epstein-Barr virus (EBV), can display several types of latent viral protein expression, denoted 0, I, IIa, IIb, or III. Of these, only type III expression induces proliferation of cells in vitro. These latency types are present at specific stages of infection and are also characteristic of different tumor types, but their generation is not fully understood. In this study, we analyzed the role of T cells in the regulation of EBV viral latency by using humanized NOD/SCID/IL2Rγ-/- mice. Several spleens presented macroscopic tumors 4 weeks after infection. Explanted spleen B cells from some of the EBV-infected mice proliferated in vitro, but this was usually lowered when cyclosporine was added to the cultures. This suggested that the in vitro growth of EBV-infected B cells required T cell help; thus, cells other than type III cells were also present in the spleens. Quantitative PCR analysis of promoter activities specific for the different EBV latency types confirmed that in addition to type III cells, type IIa and type I cells were present in the spleen. The relative usage of the viral promoter specific for I and IIa latency types (Q promoter) was higher in CD8+ cell-depleted mice, and it was absent from CD4+ cell-depleted mice. These results indicate that CD4+ T cells are necessary for the generation/maintenance of cells with latency I/IIa in the humanized mice. CD4+ T cells contributed to this process through their CD40L expression.

UR - http://www.scopus.com/inward/record.url?scp=84894595699&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894595699&partnerID=8YFLogxK

U2 - 10.1128/JVI.02885-13

DO - 10.1128/JVI.02885-13

M3 - Article

VL - 88

SP - 3235

EP - 3245

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -