EBV Persistence Involves Strict Selection of Latently Infected B Cells

Joseph, Alexandra; Babcock, Gregory J.; Thorley‐Lawson, David A.

doi:10.4049/jimmunol.165.6.2975

Cited by 92 publications

(84 citation statements)

References 38 publications

(48 reference statements)

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“…Covert infections by iridoviruses have been reported in insects (reviewed in Williams et al, 2005), although it is not clear whether these infections are quiescent as they are in mammals (i.e. EpsteinBarr virus [EBV]; Joseph et al, 2000). Quiescence provides a mechanism for viral persistence between episodes of active viral replication.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Xenopus Laevis: A Possible Vector of Ranavirus Infection?

Robert

Abramowitz

Gantress

et al. 2007

Journal of Wildlife Diseases

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ABSTRACT:Frog virus 3 (FV3) or FV3-like viruses (Iridoviridae) infect a wide range of amphibian species, and they are becoming increasingly and causally associated with amphibian disease outbreaks worldwide. We have established the frog Xenopus laevis as an experimental model to study host defense and pathogenesis of FV3 infection. Although X. laevis adults usually clear FV3 infection within a few weeks, viral DNA has been detected in the kidneys several months after they had been experimentally infected; virus also has been detected in seemingly healthy nonexperimentally infected adults. Based on this information, we hypothesized that covert FV3 infection may occur in Xenopus. We first conducted a survey that detected FV3 by polymerase chain reaction (PCR) in the kidneys (the main site of FV3 infection) in a significant fraction of X. laevis raised in five different locations in the United States. Asymptomatic FV3 carriers also were detected by initiation of an acute systemic FV3 infection in frogs that had been immunosupressed by sublethal c-irradiation. Finally, we focused on macrophages as a potential site for viral persistence, and we showed that FV3 can infect peritoneal macrophages in vitro as determined by reverse transcriptase-PCR detection of viral mRNAs. Unlike kidney cell lines that are readily killed by FV3, infected macrophages, like uninfected macrophages, survived up to 12 days. Viral transcription also was detected in macrophages from animals up to 12 days after infection. These results suggest that FV3 can become quiescent in resistant species such as Xenopus, thereby making these species potential viral reservoirs.

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Section: Discussionmentioning

confidence: 99%

“…For example, EBV infects nondividing primary B lymphocytes, and then it triggers cell proliferation. Latently infected B cells express only about 10% of the EBV genome, and they rarely support the lytic form of EBV (Joseph et al, 2000). Furthermore, as a response to a stressor, the virus can be reactivated and become infectious.…”

Section: Discussionmentioning

confidence: 99%

Xenopus Laevis: A Possible Vector of Ranavirus Infection?

Robert

Abramowitz

Gantress

et al. 2007

Journal of Wildlife Diseases

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“…This likelihood is supported by several reports indicating that EBV lytic replication occurs in terminal differentiated cells. It is now generally believed that EBV persists in resting memory B cells in which only a small fraction of the infected cells are dividing in the peripheral blood (2,24,27). Moreover, using limiting-dilution reverse transcription-PCR to detect BZLF1 and the early gene BHRF1 demonstrated that about 10 to 20% of the EBV-infected plasma cells are undergoing lytic replication, compared to fewer than 0.1% of EBV-infected germinal center B cells and memory B cells (24).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication

Huang

Wang

et al. 2007

J Virol

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Uracil-DNA glycosylases (UDGs) of the uracil-N-glycosylase (UNG) family are the primary DNA repair enzymes responsible for removal of inappropriate uracil from DNA. Recent studies further suggest that the nuclear human UNG2 and the UDGs of large DNA viruses may coordinate with their DNA polymerase accessory factors to enhance DNA replication. Based on its amino acid sequence, the putative UDG of Epstein-Barr virus (EBV), BKRF3, belongs to the UNG family of proteins, and it was demonstrated previously to enhance oriLyt-dependent DNA replication in a cotransfection replication assay. However, the expression and enzyme activity of EBV BKRF3 have not yet been characterized. In this study, His-BKRF3 was expressed in bacteria and purified for biochemical analysis. Similar to the case for the Escherichia coli and human UNG enzymes, His-BKRF3 excised uracil from single-stranded DNA more efficiently than from double-stranded DNA and was inhibited by the purified bacteriophage PBS1 inhibitor Ugi. In addition, BKRF3 was able to complement an E. coli ung mutant in rifampin and nalidixic acid resistance mutator assays. The expression kinetics and subcellular localization of BKRF3 products were detected in EBV-positive lymphoid and epithelial cells by using BKRF3-specific mouse antibodies. Expression of BKRF3 is regulated mainly by the immediateearly transcription activator Rta. The efficiency of EBV lytic DNA replication was slightly affected by BKRF3 small interfering RNA (siRNA), whereas cellular UNG2 siRNA or inhibition of cellular and viral UNG activities by expressing Ugi repressed EBV lytic DNA replication. Taking these results together, we demonstrate the UNG activity of BKRF3 in vitro and in vivo and suggest that UNGs may participate in DNA replication or repair and thereby promote efficient production of viral DNA.

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“…IgD + CD27 + cells have been characterized as non-switched memory cells or marginal zone-like B cells (9,10). Healthy asymptomatic EBV carriers have low numbers of circulating EBV + B cells that are confined mainly to the IgD 2 CD27 + compartment but can also be found among IgD + CD27 + cells (11,12).…”

Section: E Pstein-barr Virus Infection Is Commonly Contracted Inmentioning

confidence: 99%

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Sohlberg

Saghafian–Hedengren

Rasul

et al. 2013

The Journal of Immunology

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EBV, a human herpesvirus, is commonly acquired during childhood and persists latently in B cells. EBV seropositivity has been connected to immunomodulatory effects such as altered T and NK cell functional responses as well as protection against early IgE sensitization; however, owing to the asymptomatic presentation during childhood little is known regarding the infection process in children of different ages. In this study, we used mononuclear cells from cord blood and from 2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the degree of EBV-induced B cell activation and expansion differs between age groups and in particular in relationship to IFN-γ production capacity. EBV infection induced redistribution between B cell subsets with enrichment of IgD+CD27+ cells (commonly referred to as non–switched memory) in infected cord blood cell cultures, and of IgD−CD27+ cells (switched memory) in cell cultures from older children. We also related results to serostatus to CMV, a persistent herpesvirus that can affect differentiation status of T and NK cells. As compared with CMV− children, the EBV-induced enrichment of IgD−CD27+ B cells was significantly reduced in infected cell cultures from CMV+ children. This effect was associated with high levels of IFN-γ and frequencies of highly mature CD8+CD57+ T cells in CMV+ children. Our results demonstrate that both a child’s age and serostatus to CMV will have an impact on EBV-induced B cell activation and expansion, and they point to the ability of viruses with immunomodulatory functions, such as CMV, to affect immune responses within the host system.

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EBV Persistence Involves Strict Selection of Latently Infected B Cells

Cited by 92 publications

References 38 publications

Xenopus Laevis: A Possible Vector of Ranavirus Infection?

Xenopus Laevis: A Possible Vector of Ranavirus Infection?

Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

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