Rta is the principal activator of Epstein-Barr virus epithelial lytic transcription.

Autor: Ali A; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America.; National Center for Research, Khartoum, Sudan., Ohashi M; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America., Casco A; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America., Djavadian R; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America., Eichelberg M; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America., Kenney SC; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America.; Department of Medicine, Division of Infectious Diseases, University of Wisconsin, Madison, Wisconsin, United States of America., Johannsen E; Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison Wisconsin, United States of America.; Department of Medicine, Division of Infectious Diseases, University of Wisconsin, Madison, Wisconsin, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Sep 29; Vol. 18 (9), pp. e1010886. Date of Electronic Publication: 2022 Sep 29 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010886
Abstrakt: The transition from latent Epstein-Barr virus (EBV) infection to lytic viral replication is mediated by the viral transcription factors Rta and Zta. Although both are required for virion production, dissecting the specific roles played by Rta and Zta is challenging because they induce each other's expression. To circumvent this, we constructed an EBV mutant deleted for the genes encoding Rta and Zta (BRLF1 and BZLF1, respectively) in the Akata strain BACmid. This mutant, termed EBVΔRZ, was used to infect several epithelial cell lines, including telomerase-immortalized normal oral keratinocytes, a highly physiologic model of EBV epithelial cell infection. Using RNA-seq, we determined the gene expression induced by each viral transactivator. Surprisingly, Zta alone only induced expression of the lytic origin transcripts BHLF1 and LF3. In contrast, Rta activated the majority of EBV early gene transcripts. As expected, Zta and Rta were both required for expression of late gene transcripts. Zta also cooperated with Rta to enhance a subset of early gene transcripts (Rtasynergy transcripts) that Zta was unable to activate when expressed alone. Interestingly, Rta and Zta each cooperatively enhanced the other's binding to EBV early gene promoters, but this effect was not restricted to promoters where synergy was observed. We demonstrate that Zta did not affect Rtasynergy transcript stability, but increased Rtasynergy gene transcription despite having no effect on their transcription when expressed alone. Our results suggest that, at least in epithelial cells, Rta is the dominant transactivator and that Zta functions primarily to support DNA replication and co-activate a subset of early promoters with Rta. This closely parallels the arrangement in KSHV where ORF50 (Rta homolog) is the principal activator of lytic transcription and K8 (Zta homolog) is required for DNA replication at oriLyt.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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