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

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

doi:10.1016/j.molcel.2014.11.026

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.

Authors

Zoe H Davis¹, Erik Verschueren², Gwendolyn M Jang², Kevin Kleffman³, Jeffrey R Johnson², Jimin Park³, John Von Dollen², M Cyrus Maher⁴, Tasha Johnson², William Newton², Stefanie Jäger², Michael Shales², Julie Horner⁵, Ryan D Hernandez⁶, Nevan J Krogan⁷, Britt A Glaunsinger⁸

Affiliations

¹ Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Division of Infectious Diseases and Immunity, School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.
² Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁴ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
⁵ Thermo Fisher Scientific, 355 River Oaks Parkway, San Jose, CA 95134, USA.
⁶ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
⁷ Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: nevan.krogan@ucsf.edu.
⁸ Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: glaunsinger@berkeley.edu.

Abstract

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

Substances

TATA-Box Binding Protein
Viral Proteins
RNA Polymerase II

Abstract

Publication types

MeSH terms

Substances

Grants and funding