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Viruses 2016, 8(1), 8; doi:10.3390/v8010008

Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase—A Potential Strategy for Suppression of the Wnt Pathway

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore 21287, MD, USA
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Academic Editor: Eric O. Freed
Received: 23 October 2015 / Revised: 18 December 2015 / Accepted: 25 December 2015 / Published: 29 December 2015
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Abstract

Human cytomegalovirus (HCMV) was reported to downregulate the Wnt/β-catenin pathway. Induction of Axin1, the negative regulator of the Wnt pathway, has been reported as an important mechanism for inhibition of β-catenin. Since Tankyrase (TNKS) negatively regulates Axin1, we investigated the effect of HCMV on TNKS expression and poly-ADP ribose polymerase (PARsylation) activity, during virus replication. Starting at 24 h post infection, HCMV stabilized the expression of TNKS and reduced its PARsylation activity, resulting in accumulation of Axin1 and reduction in its PARsylation as well. General PARsylation was not changed in HCMV-infected cells, suggesting specific inhibition of TNKS PARsylation. Similarly, treatment with XAV939, a chemical inhibitor of TNKS’ activity, resulted in the accumulation of TNKS in both non-infected and HCMV-infected cell lines. Reduction of TNKS activity or knockdown of TNKS was beneficial for HCMV, evidenced by its improved growth in fibroblasts. Our results suggest that HCMV modulates the activity of TNKS to induce Axin1, resulting in inhibition of the β-catenin pathway. Since HCMV replication is facilitated by TNKS knockdown or inhibition of its activity, TNKS may serve as an important virus target for control of a variety of cellular processes. View Full-Text
Keywords: Human cytomegalovirus (HCMV); tankyrase; Axin1; PARsylation; ubiquitination; Wnt/β-catenin Human cytomegalovirus (HCMV); tankyrase; Axin1; PARsylation; ubiquitination; Wnt/β-catenin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Roy, S.; Liu, F.; Arav-Boger, R. Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase—A Potential Strategy for Suppression of the Wnt Pathway. Viruses 2016, 8, 8.

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