Nucleic Acids Research Advance Access originally published online on May 3, 2007
Nucleic Acids Research 2007 35(10):3391-3406; doi:10.1093/nar/gkm170
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Nucleic Acids Research, 2007, Vol. 35, No. 10 3391-3406
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Complexities associated with expression of Epstein–Barr virus (EBV) lytic origins of DNA replication
Viral Oncology Unit, Division of Medicine, Wright-Fleming Institute, Imperial College at St Mary's, Norfolk Place, London W2 1PG, UK
*To whom correspondence should be addressed. Tel: +44-207-594-3670; Fax: +44-207-410-1037; Email: b.griffin{at}imperial.ac.uk
Received February 20, 2007. Revised March 6, 2007. Accepted March 6, 2007.
EBV has two lytic origins (oriLyt) of DNA replication lying at divergent sites on the viral genome within a duplicated sequence (DS). The latter contains potential hairpin loops, ‘hinge’ elements and the promoters for transcripts from viral genes BHLF1 and LF3. These genes themselves consist largely of 125 and 102 bp repetitive sequences, respectively, and encode basic proteins. We have examined these genomic regions in detail in attempts to understand why lytic replication—necessary for virus survival—is so inefficient, and to identify controlling elements. Our studies uncovered a diverse family of promoters (P) for BHLF1 and LF3, only one pair of which (P1) proved sensitive to chemical inducing agents. The others (P2–P3/4), abutting the replication ‘core’ origin elements in DS and extending into 5'-unique sequences, may play roles in the maintenance of viral latency. We further identified a family of overlapping small complementary-strand RNAs that transverse the replication ‘core’ origin elements in a manner suggesting a role for them as ‘antisense’ species and/or DNA replication primers. Our data are discussed in terms of alternative lytic replication models. We suggest our findings might prove useful in seeking better control over viral lytic replication and devising strategies for therapy.
Present address: Department of Immunology & Molecular Pathology, Royal Free and University College Medicine School, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
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