China
Africa
Explore chapters and articles related to this topic
Epstein–Barr Virus and Treatment of Its Infection
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Tarun Jha, Amit Kumar Halder, Nilanjan Adhikari
Immediate early gene products are considered important because these are responsible for the translation from latent to lytic phase (Kieff and Rickinson 2007). These gene products also transactivate E and L gene products. The best known IE gene product is BZLF1 or Zebra. It serves as a checkpoint for initiation of the replicative cycle. BZLF1 is a DNA-binding transactivator protein involved in triggering expression of the lytic genes and downregulation of latent genes. These lead to cell death and release of infectious virions. BZLF1 protein consists of three domains: (a) one transactivation domain, (b) a basic domain with high homology to a conserved region of the c-junc/c-fos family of transcription factor, and (c) a p53-interacting domain. Overexpression of p53 protein as well as gamma irradiation induces the expression of Zebra leading to initiation of lytic cycle. The Zebra expression was also found in some EBV-associated tumor cells (Middeldorp et al. 2003). It also helps in escaping immune response by interfering with interferon γ (IFNγ) signaling. The Zebra protein reduces the expression of IFNγ and thus results in inhibition of IFNγ-induced STAT1 tyrosine phosphorylation and subsequent disruption of MHC-II upregulation (Morrison et al. 2001). Other known IE products are BRLF1, BRRF1, and BI’LF4 transactivator genes. Transcription of IE genes occurs even in the presence of protein synthesis inhibitors.
Simiao Qingwen Baidu decoction inhibits Epstein–Barr virus-induced B lymphoproliferative disease and lytic viral replication
Published in Pharmaceutical Biology, 2021
Xianhui Yang, Lingling Liu, Huijuan Zhang, Xiaoxu Sun, Yongbin Yan, Ruiying Ran
In our study, the protein expression of LMP1 was significantly increased in CGM1 cells after treated with 10%-medicated serum. Previous study has reported that low level of EBV LMP, LMP1 promotes cell proliferation by activating NF-κB signalling pathway (Dirmeier et al. 2005). However, higher level of LMP1 expression has inhibiting effect on B cell proliferation (Kaykas and Sugden 2000). Therefore, SQBD may have an inhibiting effect on B cell proliferation by regulating LMP1 expression. Moreover, the protein expression of p-p65 (canonical NF-κB signalling marker), p52 and p100 (non-canonical NF-κB signalling markers) was significantly increased by 10%-medicated serum. 10%-medicated serum caused an up-regulation of EBNA2, and had no influence on the expression of EBV latency proteins EBNA3A and EBNA3C in CGM1 cells. Since EBV transformed lymphoblasts require LMP1-induced NF-κB for their survival (Ersing et al. 2013). EBNA2-induced c-MYC and cyclin E expression play an important role in lymphoblastoid cell line proliferation (Jansen-Durr et al. 1993; Zhao et al. 2011). Thus, these data showed that SQBD inhibited B cell proliferation by regulating LMP1-medicated canonical or non-canonical NF-κB signalling pathway, and it has no effect on c-MYC-mediated transcription in EBV-transformed B cells. In addition, we also found that SQBD caused an up-regulation of BZLF1 and BMRF1. However, SQBD had no effect on the expression of late viral capsid antigen p18. Therefore, these data suggested that lytic EBV replication in CGM1 cells was inhibited by SQBD treatment.
Novel approach to identify putative Epstein–Barr–virus microRNAs regulating host cell genes with relevance in tumor biology and immunology
Published in OncoImmunology, 2022
Simon Jasinski-Bergner, Juliane Blümke, Marcus Bauer, Saskia Luise Skiebe, Ofer Mandelboim, Claudia Wickenhauser, Barbara Seliger
The combination of several other cancer hallmarks is reflected by the analysis of the gene expression pattern of factors involved in cell proliferation, cell cycle regulation as well as of known oncogenes. Many proliferation markers and known oncogenes exerted a statistically significant altered gene expression. A connection between EBV infection and higher NRAS gene expression has been published,79 while an increased PDGFB expression has been reported in NPC, independently of EBV.80 Together with the EBV-encoded LMP2A, SYK plays a role in cell migration of epithelial cells.81 The proliferation marker and cell cycle regulator E2F1 is induced by the EBV-encoded BZLF1 protein.82
Emerging therapeutic targets for nasopharyngeal carcinoma: opportunities and challenges
Published in Expert Opinion on Therapeutic Targets, 2020
Valentin Baloche, François-Régis Ferrand, Anna Makowska, Caroline Even, Udo Kontny, Pierre Busson
The proof of concept of the potential benefits of combining drugs inducing the lytic cycle with prodrugs has been made in clinical studies dealing with EBV-associated lymphomas and more recently with NPCs [106]. In a landmark study published by Wildeman et al., the lytic induction was achieved by a combination of valproic acid – used as a histone deacetylase inhibitor (HDACi) – and gemcitabin which like some other compounds of conventional chemo has proven to favor the disruption of latency in various types of EBV-infected cells. The prodrug was ganciclovir [91]. There is currently intense research in the academia and in the industry to investigate and optimize chemical inducers of the lytic cycle. A number of epigenetic modifiers are under investigation – especially HDACi – but also miscellaneous agents like tetrahydrocarboline derivatives, intra-cellular iron chelators or compounds inducing ‘unfolded protein response’ [107–109]. It seems that much less efforts are devoted to the development of adequate prodrugs. Most pre-clinical studies rely on ganciclovir or related oral compounds. Ganciclovir is activated by EBV-PK – not EBV TK – but it was initially designed as a substrate of HSV1-TK [110]. From the development of compounds specially designed for EBV enzymes, including EBV-PK and – TK, one may expect a better therapeutic index that would benefit the development of CLVA. There is also a margin of progression with regards to the biomarkers useful to monitor CLVA. Habib et al. have reported extra-cellular release of the BZLF1 protein and its detection in the plasma of AIDS patients bearing EBV-related lymphomas [111]. BZLF1 is an immediate early viral protein whose expression occurs at a very early stage of lytic activation. Its detection in the plasma of NPC patients might become a surrogate marker of lytic activation in tumor cells. However, its detection might be hampered by the concomitant presence of anti-BZLF1 antibodies which have been reported in NPC patients.