Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities

J Virol. 2003 Jun;77(11):6274-83. doi: 10.1128/jvi.77.11.6274-6283.2003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Binding Sites
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Hepatitis B virus / physiology*
  • Humans
  • Rubulavirus / physiology*
  • STAT1 Transcription Factor
  • Trans-Activators / metabolism*
  • Transfection
  • Two-Hybrid System Techniques
  • Viral Regulatory and Accessory Proteins
  • Viral Structural Proteins / metabolism*

Substances

  • DDB1 protein, human
  • DDB2 protein, human
  • DNA-Binding Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • V protein, Simian parainfluenza virus 5
  • Viral Regulatory and Accessory Proteins
  • Viral Structural Proteins
  • hepatitis B virus X protein