This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Primary infection with varicella zoster virus (VZV) results in chickenpox. VZV establishes latency in sensory ganglia and, during periods of reduced immune function, can reactivate resulting in herpes zoster (HZ, shingles), a painful and debilitating disease. One of the most severe complications following VZV infection and reactivation is vascular injury. VZV-related vasculopathy often results in stroke and can lead to blindness or permanent neurological damage. Prevention of varicella and VZV reactivation through vaccination would reduce the frequency and severity of vascular complications, but the current VZV vaccines are not completely preventive. To design better vaccines to prevent VZV reactivation, we need to identify immunodominant genes and characterize protective immune responses. To accomplish this goal, we are utilizing our novel animal model in which rhesus macaques are infected with the highly homologous Simian varicella virus (SVV). Over the last year, we have characterized SVV transcriptional activity in PBMC and BAL collected during acute primary infection as well as sensory ganglia collected during latency from the same animals. Thus far, we have analyzed 30 of the 68 unique open reading frames (genes) encoded by SVV. As expected, acute infection was associated with high levels of viral transcription whereas latency was associated with limited transcriptional activity. We have detected transcripts from immediate early viral transactivators that are also detected during lytic infection. Thus, these genes would make strong candidates for subunit vaccines. Analysis of the SVV transcriptome and the immunogenicity of highly transcribed genes will be completed next year.
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