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Viruses 2015, 7(4), 1668-1684;

Human Pirh2 is A Novel Inhibitor of Prototype Foamy Virus Replication

Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China
College of Life Sciences, Shanxi Normal University, Xi'an 710062, China
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China
Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China
Authors to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 18 December 2014 / Revised: 2 February 2015 / Accepted: 25 March 2015 / Published: 2 April 2015
(This article belongs to the Section Animal Viruses)
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Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic retroviruses. PFV causes lifelong chronic infections, which are partially attributable to a number of host cell factors that restrict viral replication. Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that Pirh2 negatively influences the Tas-dependent transcriptional activation of the PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the transactivator Tas and down-regulating its expression. In addition, the viral inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together, these results indicated that Pirh2 suppresses PFV replication by negatively impacting its transactivator Tas and the transcription of two viral promoters, which may contribute to the latency of PFV infection. View Full-Text
Keywords: PFV; Pirh2; replication; ubiquitination PFV; Pirh2; replication; ubiquitination

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Dong, L.; Cheng, Q.; Wang, Z.; Yuan, P.; Li, Z.; Sun, Y.; Han, S.; Yin, J.; Peng, B.; He, X.; Liu, W. Human Pirh2 is A Novel Inhibitor of Prototype Foamy Virus Replication. Viruses 2015, 7, 1668-1684.

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