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

Journal Article · · Virology
 [1];  [1];  [2]
  1. Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States)
  2. Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States) and Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States)

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.

OSTI ID:
20729134
Journal Information:
Virology, Journal Name: Virology Journal Issue: 2 Vol. 340; ISSN VIRLAX; ISSN 0042-6822
Country of Publication:
United States
Language:
English

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