Simian varicella virus: molecular virology

Abstract

Simian varicella virus (SVV) is a primate herpesvirus that is closely related to varicella-zoster virus (VZV), the causative agent of varicella (chickenpox) and herpes zoster (shingles). Epizootics of simian varicella occur sporadically in facilities housing Old World monkeys. This review summarizes the molecular properties of SVV. The SVV and VZV genomes are similar in size, structure, and gene arrangement. The 124.5 kilobase pair (kbp) SVV genome includes a 104.7 kbp long component covalently linked to a short component, which includes a 4.9 kbp unique short segment flanked by 7.5 kbp inverted repeat sequences. SVV DNA encodes 69 distinct open reading frames, three of which are duplicated within the viral inverted repeats. The viral genome is coordinately expressed, and immediate early (IE), early, and late genes have been characterized. Genetic approaches have been developed to create SVV mutants, which will be used to study the role of SVV genes in viral pathogenesis, latency, and reactivation. In addition, SVV expressing foreign genes are being investigated as potential recombinant varicella vaccines.

Figure 1

SVV-infected Vero cells. (A) Cytopathic effect in a SVV-infected Vero cell monolayer (20X). (B) Electron microscopy of a SVV-infected Vero cell. SVV nucleocapsids (NC) within the cell nucleus (N) and degraded virions within cell vacuoles (V) are shown. Reprinted with permission by Springer Science and Business Media from Oakes and d’Offay in Virus Diseases in Laboratory and Captive Animals 1988; 163–174. Copyright Kluwer Academic/Plenum Publishers.

Figure 2

Structure of SVV genome. The 124.7 kb SVV genome consists of a long (L) component covalently linked to a short (S) component. The L component includes a 104.0 kb unique long (UL) segment bracketed by repeat sequences. The S component includes a 4.9 kb unique short (US) segment flanked by 7.5 kb terminal (TRS) and internal (IRS) repeat sequences. The SVV left end has a 666 bp terminal element which includes a 506 bp unique sequence flanked by 80 bp inverted repeats (TRL and IRL-A), of which 65 bp are also present at the right end of the UL segment (IRL-B) (data revised from Mahalingam and Gray, 2007).

Figure 3

The SVV gene map. SVV ORFs are designated as horizontal arrows indicating gene location on each DNA strand. Potential polyadenylation sites are shown as vertical lines. The putative origins of replication (oriS) are indicated as open boxes. The R1, R2, R3, and R4 repeat elements are shown as black boxes.

Figure 4

Creation of SVV mutants and recombinant viruses using the SVV cosmid-based recombination system. The relative genomic location of each 32–38 kb SVV fragment cloned into cosmid vectors is indicated. As an example, the arrow indicates the location for insertion of translational stop codons or a foreign gene into the unique KpnI site of ORF 14 (gC gene) within CosA. Following co-transfection of Vero cells, genetic recombination occurs resulting in the generation of infectious recombinant virus harboring the specified mutation or foreign gene.