{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:50:25Z","timestamp":1789055425339,"version":"build-2803163510"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,21]]},"abstract":"<jats:p>\n                    Wildebeests carry asymptomatically\n                    <jats:italic>alcelaphine herpesvirus 1<\/jats:italic>\n                    (AlHV-1), a \u03b3-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period after transmission. Our recent findings with the rabbit model indicated that AlHV-1 infection is not productive during MCF. Here, we investigated whether latency establishment could explain this apparent absence of productive infection and sought to determine its role in MCF pathogenesis. First, whole-genome cellular and viral gene expression analyses were performed in lymph nodes of MCF-developing calves. Whereas a severe disruption in cellular genes was observed, only 10% of the entire AlHV-1 genome was expressed, contrasting with the 45% observed during productive infection in vitro. In vivo, the expressed viral genes included the latency-associated nuclear antigen homolog ORF73 but none of the regions known to be essential for productive infection. Next, genomic conformation analyses revealed that AlHV-1 was essentially episomal, further suggesting that MCF might be the consequence of a latent infection rather than abortive lytic infection. This hypothesis was further supported by the high frequencies of infected CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells during MCF using immunodetection of ORF73 protein and single-cell RT-PCR approaches. Finally, the role of latency-associated ORF73 was addressed. A lack of ORF73 did not impair initial virus replication in vivo, but it rendered AlHV-1 unable to induce MCF and persist in vivo and conferred protection against a lethal challenge with a WT virus. Together, these findings suggest that a latent infection is essential for MCF induction.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1216531110","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T00:27:35Z","timestamp":1367281655000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["An essential role for \u03b3-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle"],"prefix":"10.1073","volume":"110","author":[{"given":"Leonor","family":"Palmeira","sequence":"first","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oc\u00e9ane","family":"Sorel","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Van Campe","sequence":"additional","affiliation":[{"name":"Veterinary and Agrochemical Research Center (CODA-CERVA), B-1180 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Boudry","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Roels","sequence":"additional","affiliation":[{"name":"Veterinary and Agrochemical Research Center (CODA-CERVA), B-1180 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Myster","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Reschner","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre G.","family":"Coulie","sequence":"additional","affiliation":[{"name":"de Duve Institute, University of Louvain, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Kerkhofs","sequence":"additional","affiliation":[{"name":"Veterinary and Agrochemical Research Center (CODA-CERVA), B-1180 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Vanderplasschen","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin G.","family":"Dewals","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Immunology-Vaccinology (B43b), Faculty of Veterinary Medicine, University of Li\u00e8ge, B-4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4,29]]},"reference":[{"key":"e_1_1_2_17_11_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1995.0152"},{"key":"e_1_1_2_17_11_2_2","first-page":"58","volume-title":"Assessing the Impact of Malignant Catarrhal Fever in Ngorongoro District, Tanzania","author":"Cleaveland S","year":"2001","unstructured":"S Cleaveland, L Kusiluka, J ole Kuway, C Bell, R Kazwala Assessing the Impact of Malignant Catarrhal Fever in Ngorongoro District, Tanzania (Community-Based Animal Health and Participatory Epidemiology Unit, Organization of African Unity, University of Edinburgh), pp. 58 (2001)."},{"key":"e_1_1_2_17_11_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00286-11"},{"key":"e_1_1_2_17_11_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-42-95"},{"key":"e_1_1_2_17_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-87312-5.50023-0"},{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/467272a","article-title":"Road will ruin Serengeti","volume":"467","author":"Dobson AP","year":"2010","unstructured":"AP Dobson, et al., Road will ruin Serengeti. Nature 467, 272\u2013273 (2010).","journal-title":"Nature"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"e16370","DOI":"10.1371\/journal.pone.0016370","article-title":"Predicted impact of barriers to migration on the Serengeti wildebeest population","volume":"6","author":"Holdo RM","year":"2011","unstructured":"RM Holdo, JM Fryxell, AR Sinclair, A Dobson, RD Holt, Predicted impact of barriers to migration on the Serengeti wildebeest population. PLoS One 6, e16370 (2011).","journal-title":"PLoS One"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/B978-0-444-87312-5.50023-0","volume-title":"Virus Infections of Ruminants","author":"Plowright W","year":"1990","unstructured":"W Plowright, Malignant catarrhal fever virus. Virus Infections of Ruminants, eds Z Dinter, B Morein (Elsevier Science, Amsterdam), pp. 123\u2013150 (1990)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/1881167a0","article-title":"Blue wildebeest and the aetiological agent of bovine malignant catarrhal fever","volume":"188","author":"Plowright W","year":"1960","unstructured":"W Plowright, RD Ferris, GR Scott, Blue wildebeest and the aetiological agent of bovine malignant catarrhal fever. Nature 188, 1167\u20131169 (1960).","journal-title":"Nature"},{"key":"e_1_3_4_5_2","first-page":"56","article-title":"Malignant catarrhal fever in East Africa. I. Behaviour of the virus in free-living populations of blue wildebeest (Gorgon Taurinus Taurinus, Burchell)","volume":"6","author":"Plowright W","year":"1965","unstructured":"W Plowright, Malignant catarrhal fever in East Africa. I. Behaviour of the virus in free-living populations of blue wildebeest (Gorgon Taurinus Taurinus, Burchell). Res Vet Sci 6, 56\u201368 (1965).","journal-title":"Res Vet Sci"},{"key":"e_1_3_4_6_2","first-page":"69","article-title":"Malignant catarrhal Fever in East Africa. II. Observations on wildebeest calves at the laboratory and contact transmission of the infection to cattle","volume":"6","author":"Plowright W","year":"1965","unstructured":"W Plowright, Malignant catarrhal Fever in East Africa. II. Observations on wildebeest calves at the laboratory and contact transmission of the infection to cattle. Res Vet Sci 6, 69\u201383 (1965).","journal-title":"Res Vet Sci"},{"key":"e_1_3_4_7_2","volume-title":"The Impact of Malignant Catarrhal Fever on Maasai Pastoral Communites in Kitengela Wildlife Dispersal Area, Kenya","author":"Bedelian C","year":"2004","unstructured":"C Bedelian The Impact of Malignant Catarrhal Fever on Maasai Pastoral Communites in Kitengela Wildlife Dispersal Area, Kenya (University of Edinburgh, Edinburgh, 2004)."},{"key":"e_1_3_4_8_2","first-page":"58","volume-title":"Assessing the Impact of Malignant Catarrhal Fever in Ngorongoro District, Tanzania","author":"Cleaveland S","year":"2001","unstructured":"S Cleaveland, L Kusiluka, J ole Kuway, C Bell, R Kazwala Assessing the Impact of Malignant Catarrhal Fever in Ngorongoro District, Tanzania (Community-Based Animal Health and Participatory Epidemiology Unit, Organization of African Unity, University of Edinburgh), pp. 58 (2001)."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.tvjl.2007.11.007","article-title":"Malignant catarrhal fever: a review","volume":"179","author":"Russell GC","year":"2009","unstructured":"GC Russell, JP Stewart, DM Haig, Malignant catarrhal fever: a review. Vet J 179, 324\u2013335 (2009).","journal-title":"Vet J"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0378-1135(96)01239-4","article-title":"Characterisation of the lymphoproliferation in rabbits experimentally affected with malignant catarrhal fever","volume":"53","author":"Schock A","year":"1996","unstructured":"A Schock, HW Reid, Characterisation of the lymphoproliferation in rabbits experimentally affected with malignant catarrhal fever. Vet Microbiol 53, 111\u2013119 (1996).","journal-title":"Vet Microbiol"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1046\/j.1365-2567.2001.01154.x","article-title":"Constitutive activation of Lck and Fyn tyrosine kinases in large granular lymphocytes infected with the gamma-herpesvirus agents of malignant catarrhal fever","volume":"102","author":"Swa S","year":"2001","unstructured":"S Swa, H Wright, J Thomson, H Reid, D Haig, Constitutive activation of Lck and Fyn tyrosine kinases in large granular lymphocytes infected with the gamma-herpesvirus agents of malignant catarrhal fever. 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Vet Rec 106, 243\u2013245 (1980).","journal-title":"Vet Rec"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1297-9716-42-95","article-title":"Malignant catarrhal fever induced by Alcelaphine herpesvirus 1 is characterized by an expansion of activated CD3+CD8+CD4- T cells expressing a cytotoxic phenotype in both lymphoid and non-lymphoid tissues","volume":"42","author":"Dewals BG","year":"2011","unstructured":"BG Dewals, A Vanderplasschen, Malignant catarrhal fever induced by Alcelaphine herpesvirus 1 is characterized by an expansion of activated CD3+CD8+CD4- T cells expressing a cytotoxic phenotype in both lymphoid and non-lymphoid tissues. 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