{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:52:52Z","timestamp":1791251572388,"version":"4.1.0"},"reference-count":114,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,7,30]],"date-time":"2013-07-30T00:00:00Z","timestamp":1375142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Endonucleases catalyze critical steps in the processing, function, and turnover of many cellular <jats:styled-content style=\"fixed-case\">RNAs<\/jats:styled-content>. It is, therefore, not surprising that a number of viruses encode endonucleases that play important roles in viral gene expression. The virion host shutoff (Vhs) endonuclease of herpes simplex virus, the <jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content> protein of Kaposi Sarcoma Herpesvirus (<jats:styled-content style=\"fixed-case\">KSHV<\/jats:styled-content>), and the influenza virus <jats:styled-content style=\"fixed-case\">PB1<\/jats:styled-content> endonuclease have well\u2010characterized functions that stem from their abilities to cleave <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Vhs accelerates turnover of many cellular and viral <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content>, redirecting the cell from host to viral gene expression, counteracting key elements of the innate immune response, and facilitating sequential expression of different classes of viral genes. <jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content> reduces synthesis of many host proteins during the lytic phase of <jats:styled-content style=\"fixed-case\">KSHV<\/jats:styled-content> infections. <jats:styled-content style=\"fixed-case\">PB1<\/jats:styled-content> is a component of the influenza <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> polymerase that snatches capped oligonucleotides from cellular pre\u2010<jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content> to serve as primers during viral <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> synthesis. However, all three proteins have important second functions. Vhs stimulates translation of the 3\u2032 cistron of bicistronic <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content> that have selected cellular internal ribosome entry sites, and stimulates polysome loading and translation of selected viral <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content> at late times during productive infections. <jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content> has an alkaline exonuclease activity that is important for processing and maturation of newly synthesized copies of the <jats:styled-content style=\"fixed-case\">KSHV<\/jats:styled-content> genome. The influenza <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> polymerase binds the cap and 5\u2032 region of viral <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content> and recruits <jats:styled-content style=\"fixed-case\">eIF4G<\/jats:styled-content> and other factors to viral <jats:styled-content style=\"fixed-case\">mRNAs<\/jats:styled-content>, allowing them to be translated under conditions of reduced <jats:styled-content style=\"fixed-case\">eIF4E<\/jats:styled-content> functionality. This review will discuss the novel and expected functions of these viral endonucleases. <jats:italic>WIREs RNA<\/jats:italic> 2013, 4:693\u2013708. doi: 10.1002\/wrna.1188<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Translation &gt; Translation Mechanisms<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA Turnover and Surveillance &gt; Turnover\/Surveillance Mechanisms<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA Turnover and Surveillance &gt; Regulation of RNA Stability<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1188","type":"journal-article","created":{"date-parts":[[2013,7,30]],"date-time":"2013-07-30T18:56:56Z","timestamp":1375210616000},"page":"693-708","source":"Crossref","is-referenced-by-count":38,"title":["Virus\u2010encoded endonucleases: expected and novel functions"],"prefix":"10.1002","volume":"4","author":[{"given":"G. Sullivan","family":"Read","sequence":"first","affiliation":[{"name":"Division of Cell Biology and Biophysics University of Missouri, Kansas City Kansas City MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3160"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.78"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0309-228"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01557-12"},{"key":"e_1_2_5_6_1","first-page":"311","volume-title":"mRNA Metabolism and Post\u2010Transcriptional Gene Regulation","author":"Read GS","year":"1997"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00115-11"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01819-09"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.17.8560-8571.2002"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.15.9651-9664.2005"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.21.10272-10280.2001"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00166-10"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00137-08"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7153-7164.1999"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.12.7149-7160.1993"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-73-2-467"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1128\/jvi.61.7.2198-2207.1987","article-title":"Effects of herpes simplex virus on mRNA stability","volume":"61","author":"Strom T","year":"1987","journal-title":"J Virol"},{"key":"e_1_2_5_18_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1128\/jvi.55.3.601-610.1985","article-title":"Degradation of cellular mRNAs induced by a virion\u2010associated factor during herpes simplex virus infection of Vero cells","volume":"55","author":"Schek N","year":"1985","journal-title":"J Virol"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-65-7-1225"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1128\/jvi.46.2.498-512.1983","article-title":"Herpes simplex virus mutants defective in the virion\u2010associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of \u03b1 (immediate early) viral polypeptides","volume":"46","author":"Read GS","year":"1983","journal-title":"J Virol"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.63.5.1897-1906.1989"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.7.1926"},{"key":"e_1_2_5_23_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1128\/jvi.61.2.604-606.1987","article-title":"A mutant of herpes simplex virus type 1 exhibits increased stability of immediate\u2010early (\u03b1) mRNAs","volume":"61","author":"Oroskar AA","year":"1987","journal-title":"J Virol"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02047-07"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00615.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00005-13"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305475110"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9986"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02409-07"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2054-2061.2002"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3598-3604.2000"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.3.1063-1068.2004"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00930-12"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03049-12"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.17.9337-9345.2003"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008684"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05557-11"},{"key":"e_1_2_5_38_1","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.4049\/jimmunol.156.10.3901","article-title":"Human herpes simplex virus (HSV)\u2010specific CD8+ CTL clones recognize HSV\u20102\u2010infected fibroblasts after treatment with IFN\u2010\u03b3 or when virion host shutoff functions are disabled","volume":"156","author":"Tigges MA","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.14.6974-6986.2002"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.7.3489-3501.2004"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8245-8255.1999"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.12062"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400354101"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8582-8592.2004"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408272102"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01216-06"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.7.4090-4098.2005"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306345200"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.04.006"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600163"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.18.4969"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.13.8348-8360.2005"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00975-10"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.4.2411-2419.1996"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.1.112-122.1991"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.16.4459"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.11.6178-6187.2003"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.11.9222-9231.1999"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510712103"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01008-06"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3083"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.042"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(02)72073-4"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.1049608"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks278"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.014"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100157200"},{"key":"e_1_2_5_68_1","unstructured":"AgarwalD. Linker\u2010Insertion mutagenesis of the HSV Virion Host Shutoff (Vhs) protein: mutations that affect activity and the binding of cellular translation factors. Ph.D. Dissertation University of Missouri\u2010Kansas City 2012."},{"key":"e_1_2_5_69_1","unstructured":"SadekJS. The role of host translation factors and the exon\u2010junction complex in the control of mRNA turnover and translation by the virion host shutoff protein of herpes simplex virus. Ph.D. Dissertation University of Missouri\u2010Kansas City 2013."},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4684-4699.2004"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012377"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001583"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7536344"},{"key":"e_1_2_5_74_1","unstructured":"ShiflettLA. The herpes simplex virus virion host shutoff protein is targeted to mRNA cleavage sites through interactions with components of the host translational apparatus. Ph.D. Dissertation University of Missouri\u2010Kansas City 2011."},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1020902"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.971208"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905828106"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.2.1072-1076.2001"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.2.687-698.2003"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.16.6019-6029.2000"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18599"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.12.6859"},{"key":"e_1_2_5_83_1","first-page":"129","volume-title":"Translational Control in Biology and Medicine","author":"Doudna JA","year":"2007"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01099-9"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00055-6"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01230-12"},{"key":"e_1_2_5_87_1","first-page":"2501","volume-title":"Fields Virology","author":"Roizman B","year":"2007"},{"key":"e_1_2_5_88_1","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1128\/jvi.70.4.2124-2131.1996","article-title":"Identification and characterization of a small modular domain in the herpes simplex virus host shutoff protein sufficient for interaction with VP16","volume":"70","author":"Schmelter J","year":"1996","journal-title":"J Virol"},{"key":"e_1_2_5_89_1","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1128\/jvi.68.4.2339-2346.1994","article-title":"Herpes simplex virus VP16 forms a complex with the virion host shutoff protein vhs","volume":"68","author":"Smibert CA","year":"1994","journal-title":"J Virol"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705245104"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.12.7932-7941.1995"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01975-12"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02245-07"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00498-06"},{"key":"e_1_2_5_95_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01239-07"},{"key":"e_1_2_5_96_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01812-06"},{"key":"e_1_2_5_97_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.7.4120-4131.2005"},{"key":"e_1_2_5_98_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.8.4863-4871.1995"},{"key":"e_1_2_5_99_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1431"},{"key":"e_1_2_5_100_1","first-page":"89","volume-title":"Protein Synthesis and Translational Control","author":"Jackson RJ","year":"2012"},{"key":"e_1_2_5_101_1","unstructured":"HayesE. The mRNA degradative and IRES\u2010stimulatory activities of the herpes simplex virus virion host shutoff protein can be distinguished genetically. M.S. Thesis University of Missouri\u2010Kansas City 2013."},{"key":"e_1_2_5_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.028"},{"key":"e_1_2_5_103_1","doi-asserted-by":"publisher","DOI":"10.1042\/BC20070098"},{"key":"e_1_2_5_104_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002339"},{"key":"e_1_2_5_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00091-7"},{"key":"e_1_2_5_106_1","first-page":"2479","volume-title":"Fields Virology","author":"Pellet PE","year":"2007"},{"key":"e_1_2_5_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385032-4.00001-X"},{"key":"e_1_2_5_108_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01051-09"},{"key":"e_1_2_5_109_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611128104"},{"key":"e_1_2_5_110_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.12.7396-7401.2005"},{"key":"e_1_2_5_111_1","first-page":"1647","volume-title":"Fields Virology","author":"Palese P","year":"2007"},{"key":"e_1_2_5_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.10.028"},{"key":"e_1_2_5_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.02.012"},{"key":"e_1_2_5_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2010.12.016"},{"key":"e_1_2_5_115_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01105-07"}],"container-title":["WIREs RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fwrna.1188","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fwrna.1188","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/wrna.1188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T13:55:19Z","timestamp":1695822919000},"score":1,"resource":{"primary":{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/10.1002\/wrna.1188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,30]]},"references-count":114,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/wrna.1188"],"URL":"https:\/\/doi.org\/10.1002\/wrna.1188","archive":["Portico"],"relation":{},"ISSN":["1757-7004","1757-7012"],"issn-type":[{"value":"1757-7004","type":"print"},{"value":"1757-7012","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,30]]}}}