Prolonged gene expression in mouse lung endothelial cells following transfection with Epstein–Barr virus-based episomal plasmid

Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance.

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Epstein-Barr Virus Gene Expression in Lymphomas Induced by the Virus in the Cottontop Tamarin

Epstein-Barr Virus and Human Disease • 1988 ◽

10.1007/978-1-4612-4508-7_20 ◽

1989 ◽

pp. 141-144

Author(s):

S. Finerty ◽

L. S. Young ◽

L. Brooks ◽

F. T. Scullion ◽

A. B. Rickinson ◽

...

Keyword(s):

Gene Expression ◽

Epstein Barr Virus ◽

Virus Gene ◽

Barr Virus ◽

Virus Gene Expression ◽

Epstein Barr

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Epstein-Barr Virus Facilitates Expression of KLF14 by Regulating the Cooperative Binding of the E2F-Rb-HDAC Complex in Latent Infection

Journal of Virology ◽

10.1128/jvi.01209-20 ◽

2020 ◽

Vol 94 (22) ◽

Author(s):

Yonggang Pei ◽

Josiah Hiu-yuen Wong ◽

Hem Chandra Jha ◽

Tian Tian ◽

Zhi Wei ◽

...

Keyword(s):

Gene Expression ◽

Human Population ◽

Regulatory Networks ◽

Epstein Barr Virus ◽

Latent Infection ◽

Human Tumor ◽

Barr Virus ◽

Repressor Complex ◽

Tumor Virus ◽

Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) was discovered as the first human tumor virus more than 50 years ago. EBV infects more than 90% of the human population worldwide and is associated with numerous hematologic malignancies and epithelial malignancies. EBV establishes latent infection in B cells, which is the typical program seen in lymphomagenesis. Understanding EBV-mediated transcription regulatory networks is one of the current challenges that will uncover new insights into the mechanism of viral-mediated lymphomagenesis. Here, we describe the regulatory profiles of several cellular factors (E2F6, E2F1, Rb, HDAC1, and HDAC2) together with EBV latent nuclear antigens using next-generation sequencing (NGS) analysis. Our results show that the E2F-Rb-HDAC complex exhibits similar distributions in genomic regions of EBV-positive cells and is associated with oncogenic super-enhancers involving long-range regulatory regions. Furthermore, EBV latent antigens cooperatively hijack this complex to bind at KLFs gene loci and facilitate KLF14 gene expression in lymphoblastoid cell lines (LCLs). These results demonstrate that EBV latent antigens can function as master regulators of this multisubunit repressor complex (E2F-Rb-HDAC) to reverse its suppressive activities and facilitate downstream gene expression that can contribute to viral-induced lymphomagenesis. These results provide novel insights into targets for the development of new therapeutic interventions for treating EBV-associated lymphomas. IMPORTANCE Epstein-Barr virus (EBV), as the first human tumor virus, infects more than 90% of the human population worldwide and is associated with numerous human cancers. Exploring EBV-mediated transcription regulatory networks is critical to understand viral-associated lymphomagenesis. However, the detailed mechanism is not fully explored. Now we describe the regulatory profiles of the E2F-Rb-HDAC complex together with EBV latent antigens, and we found that EBV latent antigens cooperatively facilitate KLF14 expression by antagonizing this multisubunit repressor complex in EBV-positive cells. This provides potential therapeutic targets for the treatment of EBV-associated cancers.

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Epstein-Barr Virus Latent Gene Expression in Primary Effusion Lymphomas Containing Kaposi's Sarcoma–Associated Herpesvirus/Human Herpesvirus-8

Blood ◽

10.1182/blood.v90.3.1186.1186_1186_1191 ◽

1997 ◽

Vol 90 (3) ◽

pp. 1186-1191 ◽

Cited By ~ 8

Author(s):

Marcelo G. Horenstein ◽

Roland G. Nador ◽

Amy Chadburn ◽

Elizabeth M. Hyjek ◽

Giorgio Inghirami ◽

...

Keyword(s):

Gene Expression ◽

Viral Infection ◽

Kaposi's Sarcoma ◽

Epstein Barr Virus ◽

Kaposi’S Sarcoma ◽

Barr Virus ◽

Low Levels ◽

Kaposi's Sarcoma Associated Herpesvirus ◽

Epstein Barr ◽

Kaposi’S Sarcoma Associated Herpesvirus

Primary effusion (body cavity–based) lymphoma (PEL) is a recently recognized subtype of malignant lymphoma that exhibits distinctive clinical and biological features, most notably its usual infection with the Kaposi's sarcoma–associated herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus (EBV). This dual viral infection is the first example of a consistent dual herpesviral infection in a human neoplasm and provides a unique model to study viral interactions. We analyzed the pattern of EBV latent gene expression to determine the pathogenic role of this agent in PELs. We examined five PELs coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, a consistent marker of viral latency, was positive in all PEL cases, although at lower levels than in the non-PEL controls due to EBER1 expression by only a variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp-initiated mRNAs, encoding all EBNAs and characteristic of latency III, were negative in all cases. LMP1 mRNA, expressed in latencies II and III, was present in three cases of PEL, although at very low levels that were not detectable at the protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly positive in four cases, suggesting a productive viral infection in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases, and low LMP1 and LMP2A levels.

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