Switching of EBV cycles between latent and lytic states

Takayuki Murata, Tatsuya Tsurumi

Research output: Contribution to journalReview article

65 Citations (Scopus)

Abstract

The EBV is a human gamma-herpesvirus that is associated with a variety of neoplasms. Upon primary infection, it transiently runs a short lytic program and then predominantly establishes latent infection. Only a small percentage of infected cells switch from the latent stage into the lytic cycle and produce progeny viruses. Although EBV in cancer cells is mostly in the latent state, the lytic cycle of the virus is also expected to play a pivotal role in development and maintenance of tumors because of its association with secretion of cytokines or growth factors. Moreover, if efficient artificial induction of lytic replication could somehow be achieved, development of oncolytic therapy for EBV-positive cancers would be conceivable. Thus, understanding the switching mechanism is of essential importance. Reactivation of the virus from latency is dependent on expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical or biological inducers, such as 12-O-tetradecanoylphorbol-13-acetate, calcium ionophore, or histone deacetylase inhibitors. Transcription from the Zp is regulated by the balance between active and suppressive epigenetic histone marks, including histone acetylation, histone H3 Lysine 4 trimethylation and histone H3 lysine 27 trimethylation, being mediated by multiple transcription factors, such as myocyte enhancer factor 2, specificity protein 1, and zinc finger E-box binding homeobox. This review will focus on such molecular mechanisms by which the EBV lytic switch is controlled and discuss the physiological significance of the switching for oncogenesis.

Original languageEnglish
Pages (from-to)142-153
Number of pages12
JournalReviews in Medical Virology
Volume24
Issue number3
DOIs
Publication statusPublished - 05-2014

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All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

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