The X protein of HBV induces HIV-1 long terminal repeat transcription by enhancing the binding of C/EBPβ and CREB1/2 regulatory proteins to the long terminal repeat of HIV-1

Virus Res. 2011 Mar;156(1-2):81-90. doi: 10.1016/j.virusres.2011.01.001. Epub 2011 Jan 12.

Abstract

Due to share the route of transmission, the prevalence of co-infection of hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV-1) is high with chronic HBV infection affecting nearly 10% of HIV-infected patient world wide, which has become a significant global health problem. However, the cellular and molecular mechanisms associated with HBV/HIV-1 co-infection are largely unclear. In this study, we provided evidence that HBV induces HIV-1 transcription through its X protein (HBx). We further explored the mechanism by which HBx activates HIV-1 transcription. Our results showed that C/EBP and CRE cis-regulatory elements in the long terminal repeats (LTR) of HIV-1 are required for the activation of HIV-1 transcription mediated by HBx. We also demonstrated that HBx regulates HIV-1 transcription through stimulating the binding of transcriptional regulatory proteins C/EBPβ, CREB1, and CREB2 to HIV-1 LTR and that co-activator CBP is required for such regulation. These findings provide new insights into our understanding the effect of HBx on the activation of HIV-1 transcription and also provide evidence of the potential role of HBV in HIV-1 replication during the course of HBV/HIV-1 co-infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CREB-Binding Protein / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Viral / drug effects
  • Gene Expression Regulation, Viral / genetics
  • HEK293 Cells
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / genetics*
  • HIV-1 / metabolism*
  • HeLa Cells
  • Hepatitis B virus / metabolism*
  • Humans
  • Jurkat Cells
  • Promoter Regions, Genetic
  • Protein Binding
  • Trans-Activators / metabolism*
  • Trans-Activators / pharmacology
  • Transcription, Genetic / drug effects
  • Viral Regulatory and Accessory Proteins

Substances

  • DNA-Binding Proteins
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • CREB-Binding Protein