Simian varicella virus (SVV) and varicella-zoster virus (VZV

Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV), the causative agent of chickenpox and shingles. The SVV and VZV gene 61 polypeptides are homologs of the HSV-1 ICP0, a viral transactivator which appears to play a role in viral latency and reactivation. In this study, the molecular properties of the SVV 61 were characterized. The SVV open reading frame (ORF) 61 encodes a 54.1-kDa polypeptide with 37% amino acid identity to the VZV 61. Homology to the HSV-1 ICP-0 is limited to a conserved RING finger motif at the amino terminus of the protein. A nuclear localization sequence (nls) at the carboxy-terminus directs the SVV 61 to the cell nucleus, while a SVV 61nls(-) mutant is confined to the cell cytoplasm. The SVV 61 transactivates its own promoter as well as SVV immediate early (IE, ORF 62), early (ORFs 28 and 29), and late (ORF 68) gene promoters in transfected Vero cells. The RING finger and nls motifs are required for efficient SVV 61 transactivation. The SVV 61 has no effect on the ability of the major SVV transactivator (IE62) to induce SVV promoters. Generation and propagation of a SVV gene 61 deletion mutant demonstrated that the SVV 61 is non-essential for in vitro replication. SVV gene 61 is expressed in liver, lung, and neural ganglia of infected monkeys during acute simian varicella.

The varicella-zoster virus (VZV) Oka vaccine offers potential as a recombinant vaccine against other pathogens. In this study, recombinant simian varicella viruses (rSVV) expressing simian immunodeficiency virus (SIV) envelope (env, gp130) and gag antigens were constructed. Expression of the SIV env and gag transcripts and antigens in rSVV-infected Vero cells was confirmed. The rSVV-SIVenv and rSVV-SIVgag viruses replicated as efficiently as wild-type SVV in cell culture. The immunogenicity of rSVV-SIVenv and rSVV-SIVgag was investigated in immunized vervet monkeys. Humoral immune responses to the SIV gp130 and gag antigens were detected as early as 4 weeks after the initial immunization with higher antibody titers following a booster immunization. Cellular immune responses against the SIV gp130 antigen were detected by ELISPOT assay. The rSVV established latent infection in neural ganglia. A subsequent study will evaluate the ability of rSVV vaccines expressing SIV antigens to protect nonhuman primates against simian AIDS.

Recombinant simian varicella viruses (rSVVs) were engineered to express respiratory syncytial virus (RSV) antigens. The RSV surface glycoprotein G and second matrix protein M2 (22k) genes were cloned into the SVV genome, and recombinant viruses were characterized in vitro and in vivo. rSVVs were also engineered to express the membrane-anchored or secreted forms of the RSV-G protein as well as an RSV G lacking its chemokine mimicry motif (CX3C), which may have different effects on priming the host immune response. The RSV genes were efficiently expressed in rSVV/RSV-infected Vero cells as RSV-G and -M2 transcripts were detected by RT-PCR, and RSV antigens were detected by immunofluorescence and immunoblot assays. The rSVVs replicated efficiently in Vero cell culture. Rhesus macaques immunized with rSVV/RSV-G and rSVV/RSV-M2 vaccines produced antibody responses to SVV and RSV antigens. The results demonstrate that recombinant varicella viruses are suitable vectors for the expression of RSV antigens and may represent a novel vaccine strategy for immunization against both pathogens.