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In recent years we have analyzed the contribution of virus-encoded glycoproteins to neuroinvasion and transneuronal spread (reviewed in T. C. Mettenleiter, Virus Res. 92:197-206, 2003). We now extend our studies to analyze the role of tegument proteins in these processes. To this end, PrV mutants unable to express the UL11, UL37, UL46, UL47, and UL48 tegument proteins, as well as the corresponding rescued viruses, were intranasally instilled into 6- to 8-week-old CD1 strain mice. First, mean survival times were determined which showed that mice infected with the UL46 deletion mutant succumbed to the disease as early as wild-type PrV-infected animals. Survival times increased in the order: PrV-\u0394UL47-, PrV-\u0394UL11-, and PrV-\u0394UL48-infected animals, a finding which parallels the growth phenotype of these viruses in cell culture. In contrast, none of the PrV-\u0394UL37-infected animals died. Upon closer histological examination, all viruses except PrV-\u0394UL37 were able to infect the nasal cavity and propagate to first- and second-order neurons as shown by two-color immunofluorescence. However, neuroinvasion was delayed in PrV-\u0394UL47, PrV-\u0394UL11, and PrV-\u0394UL48, a finding that correlated with the extended survival times. Surprisingly, whereas PrV-\u0394UL48 and PrV-\u0394UL37 replicated to similar titers in cell culture which were \u223c500-fold lower than those of wild-type virus, after intranasal infection of mice PrV-\u0394UL48 was able to infect areas of the brain like wild-type PrV, although only after a considerably longer time period. In contrast, PrV-\u0394UL37 was not able to enter neurons and was restricted to the infection of single cells in the nasal respiratory epithelium. Thus, our data demonstrate the importance of herpesviral tegument proteins in neuronal infection and show a different contribution of tegument proteins to the neuroinvasion phenotype of a neurotropic alphaherpesvirus.<\/jats:p>","DOI":"10.1128\/jvi.78.6.2956-2966.2004","type":"journal-article","created":{"date-parts":[[2004,2,27]],"date-time":"2004-02-27T21:47:38Z","timestamp":1077918458000},"page":"2956-2966","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Influence of Tegument Proteins of Pseudorabies Virus on Neuroinvasion and Transneuronal Spread in the Nervous System of Adult Mice after Intranasal Inoculation"],"prefix":"10.1128","volume":"78","author":[{"given":"Robert","family":"Klopfleisch","sequence":"first","affiliation":[{"name":"Institutes of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens P.","family":"Teifke","sequence":"additional","affiliation":[{"name":"Infectology, Friedrich-Loeffler-Institutes, Federal Research Centre for Virus Diseases of Animals, D-17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institutes of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kopp","sequence":"additional","affiliation":[{"name":"Institutes of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara G.","family":"Klupp","sequence":"additional","affiliation":[{"name":"Institutes of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Mettenleiter","sequence":"additional","affiliation":[{"name":"Institutes of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0247"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-9-2277"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.4421-4426.1993"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1576"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.8.5168-5174.1992"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.46.2.371-377.1983"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1221"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8692-8699.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.5364-5372.1999"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.9.4004-4016.2000"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.2.834-845.2000"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.10.4549-4561.2000"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(84)90427-3"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9791"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.21.10259-10271.2001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.24.11608-11618.2000"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)90241-X"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7153-7164.1999"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/344278"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(08)60787-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(01)00486-2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-23-2-145"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-26-1-145"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.22.11137-11145.2001"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9975(69)90063-2"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.13.6729-6742.2002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.16.8208-8217.2002"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_3_2_30_2","first-page":"192","volume":"44","year":"1980","unstructured":"Hagemoser, W. 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