Simian varicella virus gene expression during acute and latent infection of rhesus macaques
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Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. Reactivation of VZV results in herpes zoster and other neurological complications. Our understanding of the VZV transcriptome during acute and latent infection in immune competent individuals remains incomplete. Infection of rhesus macaques with the homologous simian varicella virus (SVV) recapitulates the hallmarks of VZV infection. We therefore characterized the SVV transcriptome by quantitative real-time reverse transcriptase PCR during acute infection in bronchial alveolar lavage (BAL) cells and peripheral blood mononuclear cells, and during latency in sensory ganglia obtained from the same rhesus macaques. During acute infection, all known SVV open reading frames (ORFs) were detected, and the most abundantly expressed ORFs are involved in virus replication and assembly such as the transcriptional activator ORF 63 and the structural proteins ORF 41 and ORF 49. In contrast, latent SVV gene expression is highly restricted. ORF 61, a viral transactivator and latency-associated transcript, is the most prevalent transcript detected in sensory ganglia. We also detected ORFs A, B, 4, 10, 63, 64, 65, 66, and 68 though significantly less frequently than ORF 61. This comprehensive analysis has revealed genes that potentially play a role in the establishment and/or maintenance of SVV latency.
KeywordsHerpesvirus Simian varicella virus Gene expression Latency Rhesus macaque
We would like to thank Anj Stadnik and Kyung Park for technical assistance; the Division of Animal Resources (DAR) at the Oregon National Primate Research Center for expert animal care, especially Drs. Anne Lewis and Lois Colgin for conducting the necropsies and collecting tissues; and Alfred Legasse, Miranda Fischer, and Jesse Dewayne for collection of blood and BAL samples. This work was supported by the American Heart Association career development grant 0930234N, NIH R01AG037042, 2T32AI007472-16, NIH P51 RR00163-51, and the Brookdale Foundation.
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