DNA Sequence and Genetic Organization of the Unique Short (U s) Region of the Simian Varicella Virus Genome

Abstract

Simian varicella virus (SVV) infection of nonhuman primates is a model for the study of human varicella zoster virus (VZV) infections. The DNA sequence of the entire SVV unique short (U s) region and adjacent flanking sequences of the inverted repeats were determined. The U s region is 4904 bp in size and has a 60.9% A + T base composition. Four potential open reading frames (ORFs), designated SVUS 1, SVUS 2, SVUS 3, and SVUS 4, were identified and found to be remarkably similar in size, genetic content, and transcriptional orientation to their respective VZV U s counterparts; ORF 65, ORF 66 (U s PK), ORF 67 (gpIV), and ORF 68 (gpl). The SVUS 1 ORF encodes a putative 9 kDa homolog of the herpes simplex virus type-1 (HSV-1) U s9 tegument phosphoprotein. The SVUS 2 ORF encodes a predicted 345 amino acid polypeptide that contains a number of sequence domains conserved in cellular and viral serine/threonine (S/T) protein kinases and exhibits extensive homology with previously reported alphaherpesviral U s S/T PKs, including VZV ORF 66, HSV-1 U s3, pseudorabies virus (PRV) PK, and equine herpesvirus (EHV-1) ORF 69. The SVUS 3 and SVUS 4 ORFs exhibit features characteristic of membrane glycoproteins: an amino terminal signal sequence, potential N-linked glycosylation sites, and a large hydrophobia transmembrane domain. The predicted 353 amine acid protein encoded by SVUS 3 ORF is homologous to the VZV gpIV (ORF 67), HSV-1 gl (U s7), PRV gp63, and EHV-1 gl (ORF 73) gene products. The SVUS 4 ORF encodes a putative 604 amino acid polypeptide which exhibits extensive homology with VZV gpl and more limited homology with HSV-1 gE (U s8), PRV gpl, and EHV gE (ORF 74). This report describes the initial characterization of individual SVV genes and further defines the evolutionary relationships between SVV, VZV, and other alphaherpesviruses.