Human herpes virus 4: No bar to understanding

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  • Published: May 1, 2014
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Human herpes virus 4: No bar to understanding

Common virus

Structural and Functional Characterization of a Complex between the Acidic Transactivation Domain of EBNA2 and the Tfb1/p62 Subunit of TFIIH Credit: PLoS Pathogens et al

NMR spectroscopy has been used to investigate how a viral protein in human herpes virus 4 (also known as Epstein-Barr) regulates the activity of a second essential protein and so reveals a possible new target for the development of antiviral drugs against this common infectious agent.

Epstein-Barr is perhaps best known as the virus that causes infectious mononucleosis (more colloquially known as glandular fever or the "kissing disease". Infection is commonly via the oral route, and 9 out of 10 of us are thought to be infected, although kissing does not have to be involved in transmission but simply transfer of droplets of infected saliva). While, mononucleosis can be debilitating the same virus is also implicated in certain forms of cancer, such as Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma and several conditions associated with human immunodeficiency virus (HIV) such as hairy leukoplakia and central nervous system lymphomas. It is therefore considered an important target for drug discovery and development.

Viral trickery

Viruses such as EBV - a double-stranded DNA virus - use sophisticated strategies to subvert human cells during an infection. The viruses cannot survive outside of human cells and for this reason they have developed strategies to mimic key components of human cell function such as the RNA polymerase. Now, researchers at Université de Montréal, Canada have revealed how a component of the Epstein-Barr (EBV) virus hijacks the cell's gene-regulating machinery and so facilitates viral replication. "Unravelling the atomic level details of these interactions using structural biology allows us to understand how the virus tricks the human defence systems. Having this knowledge is the first step towards developing new therapeutic treatments for viral infections," explains Montreal's James Omichinski, who is working with Jacques Archambault of the Institut de Recherches Cliniques de Montréal (IRCM) and colleagues Philippe Chabot, Luca Raiola, Mathieu Lussier-Price, Thomas Morse and Genevieve Arseneault.

The team used heteronuclear NMR spectroscopy studies to investigate how the EBNA2 (Epstein-Barr virus nuclear antigen 2) protein of the EBV virus binds to one of the proteins of the TFIIH (general transcription factor IIH) complex that helps regulate another protein called ribonucleic acid (RNA) polymerase II, a molecule that is responsible for the control of most of our genes. "We were able to unravel the molecular details of the interaction between these proteins," explains Omichinski.

Kissing benefit

To do so, team member Philippe Chabot labelled the EBNA2 protein and TFIIH with stable isotopes for the NMR work. One direct benefit of this research is that the "kissing" interaction between the EBNA2 protein and TFIIH could become a structural focal point drug discovery.

Related Links

Plos Pathogens, 2014, 81, 430-434: "Structural and Functional Characterization of a Complex between the Acidic Transactivation Domain of EBNA2 and the Tfb1/p62 Subunit of TFIIH"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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