Abstract
Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces malignant catarrhal fever (MCF), a fatal lymphoproliferative disease of ruminants, including cattle. The strain C500 has been cloned as an infectious, pathogenic bacterial artificial chromosome (BAC) that is used to study MCF. Although AlHV-1 infection can be established in cell culture, multiple passages in vitro cause a loss of virulence associated with rearrangements of the viral genome. Here, sequencing of the BAC clone showed that the long unique region (LUR) of the genome is nearly identical to that of the previously sequenced strain from which the BAC was derived, and identified the duplication and translocation of a region from within LUR, containing the entire coding sequences of ORF50-encoding reactivation transactivator Rta and A6-encoding bZIP protein genes. The duplicated region was further located to a position within the terminal repeat (TR) and its deletion resulted in lower ORF50 expression levels and reduced viral fitness. Finally, the presence of a similar but not identical duplication and translocation containing both genes was found in AlHV-1 strain WC11. These results indicate that selection pressure for enhanced viral fitness may drive the duplication of ORF50 and A6 in AlHV-1.
Highlights
An ox developing Malignant catarrhal fever (MCF) and a blue wildebeest (Connochaetes taurinus), respectively[2,13,14]
A7 and A10 encode putative glycoproteins whereas ORF50 encodes a reactivation transactivator (Rta)[19], and A6 is a positional homolog of basic leucine zipper-encoding genes such as those encoding Epstein-Barr virus (EBV) transcription factor Zta and Kaposi’s sarcoma-associated herpesvirus (KSHV) K8 protein[20,21,22]
Little is known for alcelaphine herpesvirus 1 (AlHV-1) ORF5023, Rta orthologues in other gammaherpesviruses are essential for viral replication and reactivation from latency[19], and basic leucine zipper (bZIP) proteins like Zta are involved in the switch needed to induce the lytic phase of the EBV life cycle in latently infected B cells[22] while KSHV bZIP K8 is involved in the early stages of lytic DNA replication[21]
Summary
An ox developing MCF and a blue wildebeest (Connochaetes taurinus), respectively[2,13,14]. The entire genome of strain C500 has been cloned from low-passage, virulent virus as a bacterial artificial chromosome (BAC), in which infectivity and pathogenicity have been shown to be preserved[24]. We found that the sequence is almost identical to that of the parental strain, and we discovered and localised a duplicated and translocated region encoding ORF50 and A6 as well as partial sequences of ORF48 and A7. Since this duplication is present in a virulent BAC clone, it is not associated with a loss of pathogenicity.
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