Genome of bovine herpesvirus 5

Abstract

Here we present the complete genomic sequence of bovine herpesvirus 5 (BHV-5), an alphaherpesvirus responsible for fatal meningoencephalitis in cattle. The 138390-bp genome encodes 70 putative proteins and resembles the alpha2 subgroup of herpesviruses in genomic organization and gene content. BHV-5 is very similar to BHV-1, the etiological agent of infectious bovine rhinotracheitis, as reflected by the high level of amino acid identity in their protein repertoires (average, 82%). The highest similarity to BHV-1 products (>or=95% amino acid identity) is found in proteins involved in viral DNA replication and processing (UL5, UL15, UL29, and UL39) and in virion proteins (UL14, UL19, UL48, and US6). Among the least conserved (<or=75%) are the homologues of immediate-early (IE) proteins BICP0, BICP4, and BICP22, the three proteins being longer in BHV-5 than in BHV-1. The structure of the BHV-5 latency-related (LR) region departs markedly from that of BHV-1 in both coding and transcriptional regulatory regions. Given the potential significance of IE genes and the LR region in virus-neuron interactions, it is likely these differences contribute to BHV-5 neuropathogenicity.

FIG. 1.

Comparison of the LR regions of BHV-5 and BHV-1. The LR nucleotide positions are given above (BHV-5) and below (BHV-1) the central stippled box, and the relative nucleotide positions are in bold (1 to 3,000 bp). Restriction sites are XhoI (X), XbaI (Xb), and SphI (S). The dots above the BHV-1 LRT represent the positions of splice donor signals (27). Methionine- and non-methionine-initiated ORFs are represented by black and open boxes, respectively. Asterisks indicate the positions of in-frame stop codons. BHV-1 neuron-specific transcriptional regulatory regions NSB and NSTA are represented by boxes between XhoI and SphI sites. The hatched box in the BHV-5 regulatory region represents deleted sequences. The structure of BHV-5 frames 1 and 2 is discussed in the text and shown in detail below in Fig. 2A and B.

FIG. 2.

(A) Alignment of BHV-1 LRORF2 with translated BHV-5 genomic sequence using tfastx, indicating the homologous BHV-5 ORF in frame 2 (boxed), stop codons (*), frameshift to BHV-5 frame 3 (/), conserved substitutions (:), identities (|), and remaining open sequence in BHV-5 frame 3 (∼∼∼). Total aligned sequence (182 amino acids) is 69% identical with BHV-1 LRORF2. (B) Alignment of BHV-1 LRORF1 with translated BHV-5 sequence using tfastx. Identities and substitutions are labeled as for panel A. Total aligned sequence (367 amino acids) is 66% identical with BHV-1 LRORF1. (C) Alignment of BHV-1 and BHV-5 LR regulatory sequences represented by the hatched box in Fig. 1, using FASTA. In BHV-1, the underlined sequence 1 was specifically protected from exonuclease digestion by ganglionic nuclear factors (25); underlined sequence 2 was protected from exonuclease digestion by neuroblastoma nuclear factors (11). Potential TATA and CAT boxes are shown in bold.

FIG. 2.

(A) Alignment of BHV-1 LRORF2 with translated BHV-5 genomic sequence using tfastx, indicating the homologous BHV-5 ORF in frame 2 (boxed), stop codons (*), frameshift to BHV-5 frame 3 (/), conserved substitutions (:), identities (|), and remaining open sequence in BHV-5 frame 3 (∼∼∼). Total aligned sequence (182 amino acids) is 69% identical with BHV-1 LRORF2. (B) Alignment of BHV-1 LRORF1 with translated BHV-5 sequence using tfastx. Identities and substitutions are labeled as for panel A. Total aligned sequence (367 amino acids) is 66% identical with BHV-1 LRORF1. (C) Alignment of BHV-1 and BHV-5 LR regulatory sequences represented by the hatched box in Fig. 1, using FASTA. In BHV-1, the underlined sequence 1 was specifically protected from exonuclease digestion by ganglionic nuclear factors (25); underlined sequence 2 was protected from exonuclease digestion by neuroblastoma nuclear factors (11). Potential TATA and CAT boxes are shown in bold.