title: Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.
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.
authors.affiliation: 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.
authors.forename: Zoe H
authors.initials: ZH
authors.lastname: Davis
authors.affiliation: 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.
authors.forename: Erik
authors.initials: E
authors.lastname: Verschueren
authors.affiliation: 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.
authors.forename: Gwendolyn M
authors.initials: GM
authors.lastname: Jang
authors.affiliation: Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kleffman
authors.affiliation: 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.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jimin
authors.initials: J
authors.lastname: Park
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Von Dollen
authors.affiliation: 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.
authors.forename: M Cyrus
authors.initials: MC
authors.lastname: Maher
authors.affiliation: 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.
authors.forename: Tasha
authors.initials: T
authors.lastname: Johnson
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Newton
authors.affiliation: 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.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jäger
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.affiliation: Thermo Fisher Scientific, 355 River Oaks Parkway, San Jose, CA 95134, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Horner
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Hernandez
authors.affiliation: 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.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: glaunsinger@berkeley.edu.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Glaunsinger
mesh_terms: D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D012319:RNA Polymerase II / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D035181:TATA-Box Binding Protein; D014764:Viral Proteins; D012319:RNA Polymerase II