Abstract
Varicella-zoster virus (VZV) open reading frame 63 (ORF63) protein is expressed during latency in human
sensory ganglia. Deletion of ORF63 impairs virus replication in cell culture and establishment of latency in
cotton rats. We found that cells infected with a VZV ORF63 deletion mutant yielded low titers of cell-free virus
and produced very few enveloped virions detectable by electron microscopy compared with those infected with
parental virus. Microarray analysis of cells infected with a recombinant adenovirus expressing ORF63 showed
that transcription of few human genes was affected by ORF63; a heat shock 70-kDa protein gene was
downregulated, and several histone genes were upregulated. In experiments using VZV transcription arrays,
deletion of ORF63 from VZV resulted in a fourfold increase in expression of ORF62, the major viral transcriptional
activator. A threefold increase in ORF62 protein was observed in cells infected with the ORF63
deletion mutant compared with those infected with parental virus. Cells infected with ORF63 mutants impaired
for replication and latency (J. I. Cohen, T. Krogmann, S. Bontems, C. Sadzot-Delvaux, and L. Pesnicak,
J. Virol. 79:50695077, 2005) showed an increase in ORF62 transcription compared with those infected with
parental virus. In contrast, cells infected with an ORF63 mutant that is not impaired for replication or latency
showed ORF62 RNA levels equivalent to those in cells infected with parental virus. The ability of ORF63 to
downregulate ORF62 transcription may play an important role in virus replication and latency.
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