The genome of turkey herpesvirus

Abstract

Here we present the first complete genomic sequence of Marek's disease virus serotype 3 (MDV3), also known as turkey herpesvirus (HVT). The 159,160-bp genome encodes an estimated 99 putative proteins and resembles alphaherpesviruses in genomic organization and gene content. HVT is very similar to MDV1 and MDV2 within the unique long (UL) and unique short (US) genomic regions, where homologous genes share a high degree of colinearity and their proteins share a high level of amino acid identity. Within the UL region, HVT contains 57 genes with homologues found in herpes simplex virus type 1 (HSV-1), six genes with homologues found only in MDV, and two genes (HVT068 and HVT070 genes) which are unique to HVT. The HVT US region is 2.2 kb shorter than that of MDV1 (Md5 strain) due to the absence of an MDV093 (SORF4) homologue and to differences at the UL/short repeat (RS) boundary. HVT lacks a homologue of MDV087, a protein encoded at the UL/RS boundary of MDV1 (Md5), and it contains two homologues of MDV096 (glycoprotein E) in the RS. HVT RS are 1,039 bp longer than those in MDV1, and with the exception of an ICP4 gene homologue, the gene content is different from that of MDV1. Six unique genes, including a homologue of the antiapoptotic gene Bcl-2, are found in the RS. This is the first reported Bcl-2 homologue in an alphaherpesvirus. HVT long repeats (RL) are 7,407 bp shorter than those in MDV1 and do not contain homologues of MDV1 genes with functions involving virulence, oncogenicity, and immune evasion. HVT lacks homologues of MDV1 oncoprotein MEQ, CxC chemokine, oncogenicity-associated phosphoprotein pp24, and conserved domains of phosphoprotein pp38. These significant genomic differences in and adjacent to RS and RL regions likely account for the differences in host range, virulence, and oncogenicity between nonpathogenic HVT and highly pathogenic MDV1.

FIG. 1

Linear map of the HVT genome. Genes (colored arrows) are numbered from left to right based on positions of methionine initiation codons and transcribed in the direction indicated. Genes included in different genomic regions are defined by the color key. Nucleotide positions are indicated below the map. Spliced genes are indicated by asterisks.

FIG. 2

Accession numbers are from GenBank, SwissProt, and PIR databases; the accession number for Md5 genes is AF243438. Names for viruses: bovine herpesvirus (BHV), canine herpesvirus (CHV), duck enteritis virus (DEV), equine herpesviruses 1 and 4 (EHV-1 and -4), feline herpesvirus (FHV), herpes simplex virus (HSV), herpesvirus of turkeys (HVT), infectious laryngotracheitis virus (ILT), Marek's disease virus serotypes 1 and 2 (MDV1 and -2), varicella-zoster virus (VZV), cercopithecine herpesvirus 9 (CPHV), and avian adenovirus type 8 (Aadv8). Function was deduced either from the degree of amino acid (aa) similarity to known genes or by the presence of Prosite signatures.

FIG. 2

Accession numbers are from GenBank, SwissProt, and PIR databases; the accession number for Md5 genes is AF243438. Names for viruses: bovine herpesvirus (BHV), canine herpesvirus (CHV), duck enteritis virus (DEV), equine herpesviruses 1 and 4 (EHV-1 and -4), feline herpesvirus (FHV), herpes simplex virus (HSV), herpesvirus of turkeys (HVT), infectious laryngotracheitis virus (ILT), Marek's disease virus serotypes 1 and 2 (MDV1 and -2), varicella-zoster virus (VZV), cercopithecine herpesvirus 9 (CPHV), and avian adenovirus type 8 (Aadv8). Function was deduced either from the degree of amino acid (aa) similarity to known genes or by the presence of Prosite signatures.

FIG. 3

Multiple amino acid sequence alignment of HVT096 with Bcl-2 family members. Asterisks mark anti- and proapoptotic domains, and shaded residues indicate identity to HVT096. Gaps generated during the alignment with Pileup are indicated with dashes. Amino acid positions are indicated on the right. Rat, Rattus norvegicus, accession no. U34963; Chicken, Gallus gallus, accession no. Q07816; Quail, Coturnix japonica, accession no. X84418; BHV-4, bovine herpesvirus 4, accession no. AF129421.