Interaction of EBV latent origin of replication with the nuclear matrix: identification of S/MAR sequences and

Giulia Mearini1, Silvia Chichiarelli, Michele Zampieri

  • 1Department of Public Health Sciences, University La Sapienza, Rome, Italy. giulia.mearini@hpi.uni-hamburg.de <giulia.mearini@hpi.uni-hamburg.de>

FEBS Letters
|July 16, 2003
PubMed

Insights

Epstein Barr virus (EBV) DNA attaches to the nuclear matrix during latency via the ori P region. Specific nuclear matrix proteins bind ori P, essential for EBV

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Epstein Barr virus (EBV) establishes lifelong latency in humans.
  • During latency, the EBV genome exists as an episome attached to the host cell's nuclear matrix (NM).
  • Attachment to the NM is mediated by the latent origin of replication, ori P.

Purpose of the Study:

  • To investigate the specific EBV DNA sequences and nuclear matrix proteins involved in EBV genome attachment.
  • To understand the role of this interaction in EBV latent replication.

Main Methods:

  • Used a 580 bp DNA fragment from the EBV ori P region to identify binding sites to the nuclear matrix.
  • Employed cis-diamminedichloroplatinum cross-linking to identify interacting nuclear matrix proteins.
  • Analyzed protein-DNA interactions and their modulation during EBV lytic cycle induction.

Main Results:

  • A 580 bp region within EBV's ori P, including the DS element, demonstrated the highest affinity for the nuclear matrix.
  • Two nuclear matrix proteins (85 and 60 kDa) were identified that bind specifically to ori P.
  • These proteins are constitutively present and their interaction with ori P is disrupted during the EBV lytic cycle.

Conclusions:

  • Specific binding of EBV's ori P to nuclear matrix proteins is crucial for maintaining EBV episomal attachment.
  • This interaction is essential for Epstein Barr virus latent replication.
  • The identified proteins and their interaction represent a potential target for controlling EBV latency.