Different activation of Epstein-Barr virus immediate-early and early genes in Burkitt lymphoma cells and lymphoblastoid cell lines

Bogedain, Christoph; Alliger, Peter; Schwarzmann, Fritz; Marschall, Manfred; Wolf, Hans; Jilg, Wolfgang

doi:10.1128/jvi.68.2.1200-1203.1994

Cited by 27 publications

(10 citation statements)

References 37 publications

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“…In this case the transcriptional control of early genes would be independent of Zta, whereas another transcription transactivator may be involved in this process. In accordance with the results from the study of Bogedain et al we propose that in astrocytes, as in LCLs, where the influence of Zta expression is less efficient than in cells derived from Burkitt lymphomas, Rta could play an important transactivator role (4).…”

Section: Discussionsupporting

confidence: 91%

Epstein-Barr Virus Infection of Human Astrocyte Cell Lines

Menet

Speth

Larcher

et al. 1999

J Virol

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Epstein-Barr virus (EBV) is implicated in different central nervous system syndromes. The major cellular receptor for EBV, complement receptor type 2 (CR2) (CD21), is expressed by different astrocyte cell lines and human fetal astrocytes, suggesting their susceptibility to EBV infection. We demonstrated the infection of two astrocyte cell lines, T98 and CB193, at low levels. As infection was mediated by CR2, we used two stable CR2 transfectant astrocyte cell lines (T98CR2 and CB193CR2) to achieve a more efficient infection. We have monitored EBV gene expression for 2 months and observed the transient infection of T98 and T98CR2 cells and persistent infection of CB193 and CB193CR2 cells. The detection of BZLF1, BALF2, and BcLF1 mRNA expression suggests that the lytic cycle is initiated at early time points postinfection. At later time points the pattern of mRNA expressed (EBER1, EBNA1, EBNA2, and LMP1) differs from latency type III in the absence of LMP2A transcription and in the expression of BALF2 and BcLF1 but not BZLF1. A reactivation of the lytic cycle was achieved in CB193CR2 cells by the addition of phorbol esters. These studies identify astrocyte cell lines as targets for EBV infection and suggest that this infection might play a role in the pathology of EBV in the brain.

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Section: Discussionsupporting

confidence: 91%

Epstein-Barr Virus Infection of Human Astrocyte Cell Lines

Menet

Speth

Larcher

et al. 1999

J Virol

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“…The activation of the replicative cycle of EBV starts with the expression of immediate-early trans activators Zta, Rta, and IЈta, encoded by the reading frames BZLF1, BRLF1, and BIЈLF4 (4,16,23,25,39), respectively, which cooperate in activation of further early genes and finally result in expression of late viral proteins. In Burkitt's lymphoma (BL)-derived cell lines, Zta was shown to be the only viral trans activator able to interrupt latency and to induce the lytic replication (5,7,15). The key role of Zta in maintaining a balance between latent and lytic replication may be reflected in its control on different levels of expression.…”

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confidence: 99%

Epstein-Barr virus lytic replication is controlled by posttranscriptional negative regulation of BZLF1

Prang

Wolf

Schwarzmann

1995

J Virol

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Regulation of the immediate-early gene BZLF1 is assumed to play a key role in triggering the lytic replication of Epstein-Barr virus (EBV). The expression of BZLF1 is regulated on multiple levels, including control of transcription by several positive and negative cis-acting elements as well as posttranslational modifications and protein-protein interactions. Localization of BZLF1 on one strand of the genome and the latent EBNA1 transcription unit on the complementary strand suggests a regulatory mechanism via hybridization of antisense RNA. With a plasmid encoding a defective BZLF1 RNA, which could not be translated, we were able to induce expression of endogenous BZLF1 gene product Zta and other proteins of the lytic cycle. Our data show for the first time that latent replication is stabilized by negative regulation of an immediate-early gene of the lytic cycle by a posttranscriptional mechanism. This might be a common theme of herpes simplex virus and EBV latency.

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“…HLA types from donor cells were determined by standard serological methods. Recombinant vaccinia viruses R-Vac and Z-Vac expressing Rta and Zta, respectively, under the control of the vaccinia virus 7.5-kDa early/ late promoter were described previously (3).…”

Section: Cells and Virusesmentioning

confidence: 99%

“…Like Zta, Rta plays an important role during the switch from latency to the lytic cycle. In some cell types, such as epithelial cells, Rta alone is able to disrupt latency; in other cell types, a combination of Rta and Zta induces maximal activation of early viral promoters (3,48). We identified nine different CTL epitopes distributed over the entire Rta protein sequence.…”

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confidence: 99%

Immediate-Early Transactivator Rta of Epstein-Barr Virus (EBV) Shows Multiple Epitopes Recognized by EBV-Specific Cytotoxic T Lymphocytes

et al. 1998

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We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV) for its role as a target for specific cytotoxic T lymphocytes (CTL). Panels of overlapping peptides covering the entire amino acid sequence of Rta were synthesized and used to induce and analyze specific CTL responses in EBV-positive donors. Using peptide-pulsed target cells, we found nine different CTL epitopes that are distributed over the entire protein sequence. One epitope restricted by HLA-A24 could be mapped to the decameric sequence DYCNVLNKEF between amino acid positions 28 and 37 of the Rta protein. A second epitope could be assigned to the same region of Rta (residues 25 to 39) and was shown to be restricted by HLA-B18. Another, minimal epitope could be mapped to the nonameric sequence ATIGTAMYK between amino acid positions 134 and 142; this peptide was restricted by HLA-A11. Another four epitopes were proven to be restricted by HLA-A2, -A3, -B61, and -Cw4 and were located between Rta residues 225 and 239, 145 and 159, 529 and 543, and 393 and 407, respectively. For two other epitopes, only the location within the Rta protein is known so far (residues 121 to 135 and 441 to 455); their exact HLA restriction patterns have not yet been identified. Using target cells infected with recombinant vaccinia virus containing the gene for Rta, we showed that six of eight Rta-specific CTL lines recognized the corresponding peptides also after endogenous processing. These data suggest that Rta comprises an important target for EBV-specific cellular cytotoxicity. Together with recent findings of other immediate-early and early proteins also acting as CTL targets, they reveal the role of proteins of the lytic cycle in the immune recognition of EBV-infected cells.

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Different activation of Epstein-Barr virus immediate-early and early genes in Burkitt lymphoma cells and lymphoblastoid cell lines

Cited by 27 publications

References 37 publications

Epstein-Barr Virus Infection of Human Astrocyte Cell Lines

Epstein-Barr Virus Infection of Human Astrocyte Cell Lines

Epstein-Barr virus lytic replication is controlled by posttranscriptional negative regulation of BZLF1

Immediate-Early Transactivator Rta of Epstein-Barr Virus (EBV) Shows Multiple Epitopes Recognized by EBV-Specific Cytotoxic T Lymphocytes

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