Complete sequence and analysis of the ovine herpesvirus 2 genome

Abstract

Ovine herpesvirus 2 (OvHV-2) is endemic in sheep populations worldwide and causes malignant catarrhal fever (MCF), a lymphoproliferative disease, in cattle, bison and deer. OvHV-2 has been placed in the gammaherpesvirus subfamily and is related closely to Alcelaphine herpesvirus 1 (AlHV-1). Here, the cloning, sequencing and analysis of the complete OvHV-2 genome derived from a lymphoblastoid cell line from an affected cow (BJ1035) are reported. The unique portion of the genome consists of 130 930 bp, with a mean G+C content of 52 mol%. The unique DNA is flanked by multiple copies of terminal repeat elements 4205 bp in length, with a mean G+C content of 72 mol%. Analysis revealed 73 open reading frames (ORFs), the majority (62) of which showed homology to other gammaherpesvirus genes. A further subset of nine ORFs is shared with only the related AlHV-1. Three ORFs are entirely unique to OvHV-2, including a spliced homologue of cellular interleukin-10 that retains the exon structure of the cellular gene. The sequence of OvHV-2 is a critical first step in the study of the pathogenesis and treatment of MCF.

The Pathology of Malignant Catarrhal Fever, With an Emphasis on Ovine Herpesvirus 2

“…56,66 The genomes of OvHV-2 and AlHV-1 have been sequenced and compared. 30,33,41,138 The products of several open reading frames (ORFs) are used in transmission studies to establish whether latent or lytic infection patterns predominate in animals following challenge at different time points. 21,23,57,59,85,99,123 Expression in tissue of specific viral genes (in the case of OvHV-2, these include ORF9, DNA polymerase; ORF25, major capsid protein; ORF50, R-transactivator inducing latent to productive cycle switch; and ORF73, latency-associated nuclear antigen [LANA] homolog [genome maintenance protein]) is used to establish when productive infection occurs in the course of experimental infection.…”

A captured viral interleukin 10 gene with cellular exon structure

“…Identification of the OvHV-2 IL-10 gene During DNA sequencing of the complete OvHV-2 genome (Hart et al, 2007), analysis of the non-coding regions between open reading frames (ORFs) using the BLASTX algorithm (Altschul et al, 1990) identified a putative gene near the left terminus of the unique portion of the genome, termed Ov2.5. This had the potential to encode a homologue of other IL-10 molecules (Fig.…”

“…These M r correspond well, after accounting for the 36HA tag (3 kDa), with those predicted from sequence analysis for the nascent and mature forms of OvHV IL-10. To account for the presence in the supernatant of proteins derived from lysed cells, HEK 293T cells were transfected with pVR1255 containing an HA-tagged cDNA of the OvHV-2 Ov2 gene (Hart et al, 2007), the product of which is known to have an M r of 40 000 on SDS-PAGE gels and a nuclear/ cytoplasmic distribution. An Ov2-HA product was contained only in the cell pellet.…”

“…While AlHV-1 has been isolated and completely sequenced (Ensser et al, 1997), the study of OvHV-2 has lagged behind due to a lack of suitable culture systems. Recently, however, the complete sequence of OvHV-2 has been determined based on cosmid clones from an infected cell line (Hart et al, 2007) and was confirmed by sequencing of DNA prepared from sheep-derived OvHV-2 virions (Taus et al, 2007).…”

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

“…The viral DNA was detected in all 30 samples examined with a mean copy number of 3.124 Â 10 6 per 500 ng of tissue DNA ranging from $300 to 3 Â 10 7 copies ( (Hart et al, 2007). ORF73 codes for a homolog of the gammaherpesvirus latency-associated nuclear protein, which is involved in viral genome maintenance and expressed during lytic and latent infection (Ahn et al, 2002;Gailbreath et al, 2008;Hart et al, 2007).…”