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Virology Journal
Published in: Virology Journal 1/2015

Open Access 01-12-2015 | Research

Agnoprotein of polyomavirus BK interacts with proliferating cell nuclear antigen and inhibits DNA replication

Authors: Nancy Gerits, Mona Johannessen, Conny Tümmler, Mari Walquist, Sergiy Kostenko, Igor Snapkov, Barbara van Loon, Elena Ferrari, Ulrich Hübscher, Ugo Moens

Published in: Virology Journal | Issue 1/2015

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Abstract

Background

The human polyomavirus BK expresses a 66 amino-acid peptide referred to as agnoprotein. Though mutants lacking agnoprotein are severely reduced in producing infectious virions, the exact function of this peptide remains incompletely understood. To elucidate the function of agnoprotein, we searched for novel cellular interaction partners.

Methods

Yeast-two hybrid assay was performed with agnoprotein as bait against human kidney and thymus libraries. The interaction between agnoprotein and putative partners was further examined by GST pull down, co-immunoprecipitation, and fluorescence resonance energy transfer studies. Biochemical and biological studies were performed to examine the functional implication of the interaction of agnoprotein with cellular target proteins.

Results

Proliferating cell nuclear antigen (PCNA), which acts as a processivity factor for DNA polymerase δ, was identified as an interaction partner. The interaction between agnoprotein and PCNA is direct and occurs also in human cells. Agnoprotein exerts an inhibitory effect on PCNA-dependent DNA synthesis in vitro and reduces cell proliferation when ectopically expressed. Overexpression of PCNA restores agnoprotein-mediated inhibition of cell proliferation.

Conclusion

Our data suggest that PCNA is a genuine interaction partner of agnoprotein and the inhibitory effect on PCNA-dependent DNA synthesis by the agnoprotein may play a role in switching off (viral) DNA replication late in the viral replication cycle when assembly of replicated genomes and synthesized viral capsid proteins occurs.
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Metadata
Title
Agnoprotein of polyomavirus BK interacts with proliferating cell nuclear antigen and inhibits DNA replication
Authors
Nancy Gerits
Mona Johannessen
Conny Tümmler
Mari Walquist
Sergiy Kostenko
Igor Snapkov
Barbara van Loon
Elena Ferrari
Ulrich Hübscher
Ugo Moens
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2015
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-014-0220-1

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