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Title: Characterization of ovine herpesvirus 2-induced malignant catarrhal fever in rabbits

item Li, Hong
item Cunha, Cristina
item Gailbreath, Katherine
item O'TOOLE, DONAL - University Of Wyoming
item White, Stephen
item VANDERPLASSCHEN, A - University De Liege
item DEWALS, B - University De Liege
item Knowles Jr, Donald
item Taus, Naomi

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2011
Publication Date: 6/2/2011
Citation: Li, H., Cunha, C.W., Gailbreath, K.L., O'Toole, D., White, S.N., Vanderplasschen, A., Dewals, B., Knowles Jr, D.P., Taus, N.S. 2011. Characterization of ovine herpesvirus 2-induced malignant catarrhal fever in rabbits. Veterinary Microbiology. 150(3-4):270-7.

Interpretive Summary: Malignant catarrhal fever (MCF), a frequently fatal disease of certain ruminant species, such as cattle, and bison, is mainly caused by two viruses: Ovine herpesvirus 2 (OvHV-2) carried by sheep, Alcelaphine herpesvirus 1 (AlHV-1) carried by wildebeest. Although the diseases induced by both viruses are indistinguishable, recent studies revealed some fundamental differences between the two viruses in disease development. This study was designed to further confirm that rabbits can be used as an animal model for studies of OvHV-2-inducd MCF, and to determine how OvHV-2 replicates in rabbits in comparison with the disease in rabbits induced by AlHV-1, wildebeest-associated MCF virus. In this study, all six rabbits infected with OvHV-2 developed MCF. OvHV-2 DNA levels in peripheral blood remained undetectable during the incubation period and increased dramatically a few days before onset of clinical signs, which are very similar to what occurred in the rabbits with AlHV-1 induced MCF. However, two major differences were found in this study: 1) OvHV-2 induced MCF in rabbits is predominantly associated with viral replication; in contrast, AlHV-1 induced MCF in rabbits is associated with viral latency (non-replication); 2) OvHV-2 induces proliferation of all types of lymphocytes in diseased rabbits, while AlHV-2 induces proliferation of only one type of lymphocytes (called CD8+ cells). The data suggest that OvHV-2 and AlHV-1 employ different mechanisms in disease development.

Technical Abstract: Malignant catarrhal fever (MCF) is a frequently fatal lymphoproliferative disease syndrome primarily of ruminant species, caused by gammaherpesviruses in the genus Macavirus. Ovine herpesvirus 2 (OvHV-2),carried by sheep,causes sheep-associated MCF worldwide,while Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest,causes wildebeest-associated MCF, mainly in Africa. Diseases in rabbits can be induced by both viruse, which are clinically and pathologically similar; however, recent studies revealed different expression of viral genes associated with latency or lytic replication during clinical disease between the two viruses. In this study, we further characterized experimentally induced MCF in rabbits by nebulization with OvHV-2 from sheep nasal secretions to elucidate the course of viral replication, along with in vivo incorporation of 5-Bromo-2’-Deoxyuridine (BrdU), to evaluate lymphoproliferation. All six rabbits nebulized with OvHV-2 developed MCF between 24 and 29 days post infection. OvHV-2 DNA levels in peripheral blood leukocytes (PBL) remained undetectable during the incubation period and increased dramatically a few days before onset of clinical signs. During clinical stage, we found that predominantly lytic gene expression was detected in PBL and tissues, and both T and B cells were proliferating. The data showed that the viral gene expression profile and lymphoproliferation in rabbits with OvHV-2 induced MCF were different from that in rabbits with AIHV-1 induced MCF, suggesting that OvHV-2 and AIHV-1 may play a different role in MCF pathogenesis.