Epstein-Barr virus-encoded small RNAs (EBERs) do not modulate interferon effects in infected lymphocytes

Swaminathan, Sankar; Huneycutt, Brandon S.; Reiss, Carol Shoshkes; Kieff, Elliott

doi:10.1128/jvi.66.8.5133-5136.1992

Cited by 53 publications

(14 citation statements)

References 21 publications

(18 reference statements)

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“…Our experiments also utilized LCLs and PB-MCs from an adult seronegative donor, suggesting that the observed IFN--y response is due to nonspecific immunity and may be NK cell mediated. The levels of IFN--y detectable in these cultures are similar to those which can block primary B-lymphocyte transformation in vitro (20,38). IFN-y secretion also occurs in PBMCs from seropositive donors infected with cell-free virus; in this case, the primary source of secreted IFN is believed to be the CD4+ T lymphocyte (2).…”

Section: Discussionmentioning

confidence: 83%

“…Eight of the BCRF1-deleted virus mutants were passaged in this manner. Transformed cell lines became macroscopically visible 3 to 4 weeks after cocultivation and were expanded to growth in bulk without difficulty, as is characteristic of WT recombinant virus passaged by cocultivation (38). Growth of the newly transformed LCLs at 6 weeks was also indistinguishable from growth of LCLs infected with WT BCRF1 recombinants, with a doubling time of 48 to 72 h. This assay can detect differences in growth-transforming properties of mutant EBV recombinants as shown for mutant EBNA-LP EBV recombinants (23).…”

Section: !-mentioning

confidence: 94%

“…The infected cells were plated into 320 microwells and fed weekly with complete medium. PBMCs were isolated on a Ficoll-Hypaque gradient as previously described (38).…”

Section: Sal Pdvcosa2 Salmentioning

confidence: 99%

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Epstein-Barr virus recombinants with specifically mutated BCRF1 genes

Swaminathan

Hesselton

Sullivan

et al. 1993

J Virol

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Epstein-Barr virus (EBV) recombinants with specifically mutated BCRF1 genes were constructed and compared with wild-type BCRF1 recombinants derived in parallel for the ability to initiate and maintain latent infection and growth transformation in primary human B lymphocytes. A stop codon insertion after codon 116 of the 170-codon BCRF1 open reading frame or deletion of the entire gene had no effect on latent infection, B-lymphocyte proliferation into long-term lymphoblastoid cell lines (LCLs), or virus replication. LCLs infected with the stop codon recombinant were indistinguishable from wild-type recombinant-infected LCLs in tumorigenicity in SCID mice. However, mutant BCRF1 recombinant-infected cells differed from wild-type recombinant-infected cells in their inability to block gamma interferon release in cultures of permissively infected LCLs incubated with autologous human peripheral blood mononuclear cells. This is the first functional assay for BCRF1 expression from the EBV genome. BCRF1 probably plays a key role in modulating the specific and nonspecific host responses to EBV infection.

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Section: Discussionmentioning

confidence: 83%

Section: !-mentioning

confidence: 94%

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Epstein-Barr virus recombinants with specifically mutated BCRF1 genes

Swaminathan

Hesselton

Sullivan

et al. 1993

J Virol

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“…Other studies also indirectly argue against PKR being an important target of EBERs. B cell lines transformed by EBV in which the EBER genes were specifically deleted are no more sensitive to the antiviral effects of interferon as measured by their ability to support VSV replication (Swaminathan et al, 1992). Similarly, when EBER‐positive cells were infected with a VAI‐deleted adenovirus, they were able to support replication of the defective adenovirus but PKR phosphorylation was not significantly altered, suggesting that EBERs may actually rescue VAI‐deleted adenovirus by a PKR‐independent mechanism (Wang et al, 2005).…”

Section: Ebv‐encoded Small Rnasmentioning

confidence: 99%

Noncoding RNAs produced by oncogenic human herpesviruses

Swaminathan

2008

Journal Cellular Physiology

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The two human herpesviruses that are causally associated with cancer are Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus (KSHV). Both are lymphocryptoviruses that establish latency in B lymphocytes and persist for the lifetime of the host. EBV and KSHV are both linked to a variety of lymphomas. EBV is also a causative agent or cofactor in epithelial malignancies such as nasopharyngeal carcinoma whereas Kaposi’s sarcoma is of endothelial cell origin. Both viruses encode a limited number of proteins during latent replication that are important for growth transformation and evasion of the immune system. In addition, they express noncoding RNAs during both latent and lytic infection. Many of these RNAs have been highly conserved during evolution and are expressed in a wide variety of clinical settings, suggesting their fundamental importance in the viral life cycle. The function of some of these RNAs such as the nuclear EBV EBER RNAs remains elusive although they are some of the most abundant transcripts produced by each virus. Both EBV and KSHV also have recently been shown to encode and express microRNAs. The study of these viral microRNAs is just beginning although several of their cellular and viral gene targets have been established. Viral microRNAs appear to be involved in both modulation of the immune response as well as oncogenesis. Because each target gene may have many microRNAs acting on its mRNA, and each microRNA may have more than one target, there are likely to be many new discoveries regarding the complex interactions of viral microRNAs and host cell genes.

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“…In different reports on the localization of the EBERs, these RNAs were found either in the nucleus (10) or near the nuclear membrane in the cytoplasm (18), obviously tightly associated with the polyribosomes. On the basis of the homology of these RNAs to the small untranslated RNAs VAI and VAII of adenovirus (15), a highly plausible role for the EBERs is the modulation of interferon-mediated antiviral responses by binding to and inactivation of the interferon-induced DAI kinase (19)(20)(21). Furthermore, binding of the EBERs to ribosomal protein L22 was shown (23), suggesting a role in the regulation of translation.…”

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confidence: 99%

Epstein-Barr Virus Small RNA (EBER) Genes: Differential Regulation during Lytic Viral Replication

et al. 1998

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In every latently Epstein-Barr virus-infected cell the viral genes EBER-1 and EBER-2 are transcribed by polymerase III. In lytically infected cells in vivo the EBER genes could not be detected. However, in cell culture downregulation could not be confirmed, and hence the relevance of this shutdown to the replication of the virus was not clear. We assayed the transcriptional activity of the EBER genes by nuclear run-on assays with enriched lytically infected cells and demonstrated that EBER-1 and EBER-2 are differentially downregulated on the transcriptional level during the switch to lytic viral replication. This downregulation was an early event during the lytic replication of the virus.

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Epstein-Barr virus-encoded small RNAs (EBERs) do not modulate interferon effects in infected lymphocytes

Cited by 53 publications

References 21 publications

Epstein-Barr virus recombinants with specifically mutated BCRF1 genes

Epstein-Barr virus recombinants with specifically mutated BCRF1 genes

Noncoding RNAs produced by oncogenic human herpesviruses

Epstein-Barr Virus Small RNA (EBER) Genes: Differential Regulation during Lytic Viral Replication

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