biostudies-literatureDavis ZHNIAID NIH HHSNHGRI NIH HHSNCI NIH HHSNIGMS NIH HHS349-60https://www.ebi.ac.uk/biostudies/studies/S-EPMC4305015biostudies-literatureUnknown57(2)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.Molecular cellGlobal mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.PMC4305015R01 CA160556R01HG007644R01 CA136367P50 GM082250P30 AI027763P01 CA177322U54 AI081680R01 HG007644P01 AI091575CA136367CA160556P50 GM081879P01 AI090935F31 CA180609-01F31 CA180609Krogan NJPark JJang GMMaher MCHernandez RDVon Dollen JShales MJohnson TDavis ZHKleffman KVerschueren ENewton WHorner JGlaunsinger BAJohnson JRJager SfalseGlobal mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.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.2015-01-01T00:00:00Z2015 Jan2024-11-12T17:46:25.066Z2019-03-27T01:44:03ZS-EPMC43050152554456310.1016/j.molcel.2014.11.026