Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes

Mol Cell. 2015 Jan 22;57(2):349-60. doi: 10.1016/j.molcel.2014.11.026. Epub 2014 Dec 24.


Mapping host-pathogen interactions has proven instrumental for understanding how viruses manipulate host machinery and how numerous cellular processes are regulated. DNA viruses such as herpesviruses have relatively large coding capacity and thus can target an extensive network of cellular proteins. To identify the host proteins hijacked by this pathogen, we systematically affinity tagged and purified all 89 proteins of Kaposi's sarcoma-associated herpesvirus (KSHV) from human cells. Mass spectrometry of this material identified over 500 virus-host interactions. KSHV causes AIDS-associated cancers, and its interaction network is enriched for proteins linked to cancer and overlaps with proteins that are also targeted by HIV-1. We found that the conserved KSHV protein ORF24 binds to RNA polymerase II and brings it to viral late promoters by mimicking and replacing cellular TATA-box-binding protein (TBP). This is required for herpesviral late gene expression, a complex and poorly understood phase of the viral lifecycle.

Publication types

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

MeSH terms

  • Gene Expression Regulation, Viral
  • HEK293 Cells
  • Herpesvirus 8, Human / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • RNA Polymerase II / metabolism
  • TATA-Box Binding Protein / metabolism
  • Transcription, Genetic*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • TATA-Box Binding Protein
  • Viral Proteins
  • RNA Polymerase II