Simian varicella virus gene expression during acute and latent infection of rhesus macaques
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Simian varicella virus gene expression during acute and latent infection of rhesus macaques Christine Meyer & Amelia Kerns & Alex Barron & Craig Kreklywich & Daniel N. Streblow & Ilhem Messaoudi
Received: 28 July 2011 / Revised: 26 September 2011 / Accepted: 6 October 2011 / Published online: 4 November 2011 # Journal of NeuroVirology, Inc. 2011
Abstract Varicella zoster virus (VZV) is a neurotropic αherpesvirus 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 Electronic supplementary material The online version of this article (doi:10.1007/s13365-011-0057-y) contains supplementary material, which is available to authorized users. C. Meyer : A. Kerns : A. Barron : D. N. Streblow : I. Messaoudi Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, USA C. Meyer : C. Kreklywich : D. N. Streblow : I. Messaoudi Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, USA I. Messaoudi Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, USA C. Kreklywich Department of Surgery, Oregon Health and Science University, Portland, USA I. Messaoudi (*) Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006, USA e-mail: [email protected]
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. Keywords Herpesvirus . Simian varicella virus . Gene expression . Latency . Rhesus macaque
Introduction Primary infection with varicella zoster virus (VZV), a neurotropic α-herpesvirus, results in chickenpox (varicella). VZV then establishes a lifelong latent infection in sensory ganglia such as the trigeminal and dorsal root ganglia. Reactivation of VZV leads to herpes zoster (shingles), which c
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