Processivity factor of KSHV contains a nuclear localization signal and binding domains for transporting viral DNA polymerase into the nucleus

Virology. 2005 Sep 30;340(2):183-91. doi: 10.1016/j.virol.2005.06.017.


Kaposi's sarcoma-associated human herpesvirus (KSHV) encodes a processivity factor (PF-8, ORF59) that forms homodimers and binds to viral DNA polymerase (Pol-8, ORF9). PF-8 is essential for stabilizing Pol-8 on template DNA so that Pol-8 can incorporate nucleotides continuously. Here, the intracellular interaction of these two viral proteins was examined by confocal immunofluorescence microscopy. When individually expressed, PF-8 was observed exclusively in the nucleus, whereas Pol-8 was found only in the cytoplasm. However, when co-expressed, Pol-8 was co-translocated with PF-8 into the nucleus. Mutational analysis revealed that PF-8 contains a nuclear localization signal (NLS) as well as domains located at the N-terminus and the C-proximal regions that are required for Pol-8 binding. This study suggests that the mechanism that enables PF-8 to transport Pol-8 into the nucleus is the first critical step required for Pol-8 and PF-8 to function processively in KSHV DNA synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Cytoplasm / metabolism
  • DNA Primers
  • DNA Replication
  • DNA, Viral / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Herpesvirus 8, Human / enzymology*
  • Herpesvirus 8, Human / genetics
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Protein Transport
  • Signal Transduction
  • Transfection
  • Vero Cells
  • Viral Proteins / metabolism


  • DNA Primers
  • DNA, Viral
  • Viral Proteins
  • DNA-Directed DNA Polymerase