Abstract
Ovine herpesvirus-2 (OvHV-2) is the causative agent of the sheep-associated form of malignant catarrhal fever, a usually fatal lymphoproliferative disease of bison, deer and cattle. Malignant catarrhal fever is a major cause of cattle loss in Africa with approximately 7% affected annually; and in North America has significant impact on bison farming. Research into the mechanisms by which OvHV-2 induces disease in susceptible species has been hampered by a lack of a cell culture system for the virus. Ov2 is a bZIP protein encoded by OvHV-2. Proteins with bZIP domains in other herpesviruses, such as the Kaposi’s sarcoma-associated herpesvirus K8 protein and the BZLF1 protein of Epstein-Barr virus are known to play important roles in lytic virus replication. Using a reporter based system, we demonstrate that Ov2 can modulate the activity of the major virus transactivator (Replication and Transcriptional Activator protein, RTA) to 1) drive expression of viral genes predicted to be required for efficient reactivation of the virus, including ORF49; and 2) differentially regulate the expression of the two virus encoded Bcl-2 homologues Ov4.5 and Ov9.
Highlights
Malignant catarrhal fever (MCF) is a usually fatal disease of cattle, deer, bison and other ruminants caused by viruses in the genus Macavirus of the subfamily Gammaherpesvirinae (McGeoch et al 2006)
The two most common forms of MCF detected are the sheep associated form of the disease caused by Ovine herpesvirus 2 (OvHV-2) and the wildebeest associated form of disease caused by Alcelaphine herpesvirus 1 (AlHV-1)
No tissue culture system is available to study the role of specific virus encoded proteins in OvHV-2 replication to investigate if Ov2 either alone, or in concert with the OvHV-2 replication and transcription activator (RTA), could activate or repress transcription from a variety of viral promoters, a luciferase based reporter gene system was utilised
Summary
Malignant catarrhal fever (MCF) is a usually fatal disease of cattle, deer, bison and other ruminants caused by viruses in the genus Macavirus of the subfamily Gammaherpesvirinae (McGeoch et al 2006). The two most common forms of MCF detected are the sheep associated form of the disease caused by Ovine herpesvirus 2 (OvHV-2) and the wildebeest associated form of disease caused by Alcelaphine herpesvirus 1 (AlHV-1). Infect and establish a lifelong latent infection, within lymphocytes of sheep or wildebeest, making these species reservoir hosts. Reactivation of these viruses, and the other Macaviruses from latency within reservoir populations, resulting in shedding of the virus in nasal secretions, poses an infection risk to MCF susceptible species, such as cattle, bison and deer (O'Toole and Li 2014). Shedding of OvHV-2 in nasal secretions from both adolescent and adult sheep appears to occur in short, sharp bursts that suggest a relatively tightly controlled reactivation process (Li et al 2014)
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