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Journal of Virology, June 2003, p. 6274-6283, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6274-6283.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities

Olivier Leupin, Séverine Bontron, and Michel Strubin*

Department of Genetics and Microbiology, University Medical Centre (C.M.U.), 1211 Geneva 4, Switzerland

Received 20 September 2002/ Accepted 28 February 2003

The UV-damaged DNA-binding activity protein (UV-DDB) consists of two subunits, DDB1 and DDB2, and functions in DNA repair and cell cycle regulation. The DDB1 subunit is a target for the hepatitis B virus X protein (HBx). Binding of HBx to DDB1 interferes with cell growth and viability in culture and has been implicated in the establishment of viral infection. DDB1 also interacts with the V proteins encoded by several paramyxoviruses including simian virus 5 (SV5), which prevent interferon signaling by targeting either STAT1 or STAT2 proteins for proteolysis. The role of V binding to DDB1, however, remains unclear. Here we show that the V protein of SV5 (SV5-V) and HBx exhibit strikingly similar DDB1 binding properties. Thus, SV5-V and HBx bind to DDB1 in a mutually exclusive manner, and SV5-V shares with HBx the ability to enhance the steady-state levels of DDB1 and to inhibit its association with DDB2. Yet only HBx induces cell death, and SV5-V can prevent HBx from doing so by blocking its interaction with DDB1. Binding of SV5-V to DDB1 may serve another function, since SV5-V shows a decreased ability to induce STAT1 degradation in cells expressing reduced amounts of DDB1. These findings demonstrate that HBx performs a unique function through its association with DDB1 for which SV5-V cannot substitute and suggest that SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions, both by a mechanism that does not involve DDB2.

* Corresponding author. Mailing address: Department of Genetics and Microbiology, University Medical Centre (C.M.U.), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Phone: (4122) 379 5647. Fax: (4122) 379 5702. E-mail: Michel.Strubin{at}medecine.unige.ch.

Journal of Virology, June 2003, p. 6274-6283, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6274-6283.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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