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1 Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
2 Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
Correspondence
Adrian Whitehouse
a.whitehouse{at}leeds.ac.uk
Herpesvirus saimiri (HVS) establishes a latent infection in which the viral genome persists as a non-integrated episome. Analysis has shown that only open reading frames (ORFs) 7173 are transcribed in an in vitro model of HVS latency. ORF73 also colocalizes with HVS genomic DNA on host mitotic chromosomes and maintains the stability of HVS terminal-repeat-containing plasmids. However, it is not known whether ORF73 is the only HVS-encoded protein required for episomal maintenance. In this study, the elements required for episomal maintenance in the context of a full-length HVS genome were examined by mutational analysis. A recombinant virus, HVS-BAC
71-73, lacking the latency-associated genes was unable to persist in a dividing cell population. However, retrofitting an ORF73 expression cassette into the recombinant virus rescued episomal maintenance. This indicates that ORF73 is the key trans-acting factor for episomal persistence and efficient establishment of a latent infection.
These authors contributed equally to this work.
Present address: The Channing Laboratory, Brigham and Women's Hospital and Departments of Medicine, Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA.
Present address: Imperial College School of Medicine, St Mary's Hospital Campus, Norfolk Place, London W2 1PG, UK.
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