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Antibodies to several EBV\u2010encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV\u2010encoded proteins in the etiology of these and other EBV\u2010associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen\u2010stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon\u2010\u03b3 after re\u2010stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase\u2010treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease. J. Med. Virol. 74:442\u2013448, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.20196","type":"journal-article","created":{"date-parts":[[2004,9,14]],"date-time":"2004-09-14T16:02:13Z","timestamp":1095177733000},"page":"442-448","source":"Crossref","is-referenced-by-count":24,"title":["Epstein\u2013Barr virus\u2010encoded dUTPase modulates immune function and induces sickness behavior in mice"],"prefix":"10.1002","volume":"74","author":[{"given":"David A.","family":"Padgett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew K.","family":"Hotchkiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah M.","family":"Pyter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy J.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peir\u2010En","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Litsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marshall","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Glaser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,14]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-8-reviews3011"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/310207a0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00343-6"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2001.1915"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(80)90524-3"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.10.6162"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(02)84005-2"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb05827.x"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.663"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(97)00033-1"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(98)00160-0"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(91)90018-6"},{"key":"e_1_2_1_14_1","first-page":"189","article-title":"The importance of viral markers in the study of Epstein\u2013Barr virus\u2010associated illness","volume":"85","author":"Glaser R","year":"1987","journal-title":"Bull Inst Pasteur"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-142-37176"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"8617","DOI":"10.1016\/S0021-9258(17)34337-5","article-title":"Two Epstein\u2013Barr virus\u2010associated DNA polymerase activities","volume":"253","author":"Goodman SR","year":"1978","journal-title":"J Biol Chem"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000069517"},{"key":"e_1_2_1_18_1","first-page":"361","article-title":"Antibodies to Epstein\u2013Barr virus\u2010related antigens in nasopharyngeal carcinoma. 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