Details

Autor(en) / Beteiligte

• Davis, Zoe H.
• Verschueren, Erik
• Jang, Gwendolyn M.
• Kleffman, Kevin
• Johnson, Jeffrey R.
• Park, Jimin
• Von Dollen, John
• Maher, M. Cyrus
• Johnson, Tasha
• Newton, William
• Jäger, Stefanie
• Shales, Michael
• Horner, Julie
• Hernandez, Ryan D.
• Krogan, Nevan J.
• Glaunsinger, Britt A.

Titel

Global Mapping of Herpesvirus-Host Protein Complexes Reveals a Transcription Strategy for Late Genes

Ist Teil von

• Molecular cell, 2015-01, Vol.57 (2), p.349-360

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •A herpesvirus-human protein interactome was systematically assembled in human cells•The KSHV interaction network is a tool for predicting viral protein functions•KSHV ORF24 recruits RNA polymerase II and replaces human TBP at late promoters Kaposi’s sarcoma-associated herpesvirus (KSHV) is a major AIDS-associated pathogen. Davis et al. assemble a KSHV-host protein-protein interaction network that suggests herpesvirus-host evolutionary interplay. Using the network, they describe a hybrid KSHV-human transcription complex that activates viral late genes.