Complexities associated with expression of Epstein-Barr virus (EBV) lytic origins of DNA replication

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 consi...

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Bibliographic Details
Published in:Nucleic acids research 2007-05, Vol.35 (10), p.3391-3406
Main Authors: Xue, Shao-An, Griffin, Beverly E
Format: Article
Language:English
Subjects:
Animals
Cell Line
DNA Replication
DNA, Viral - biosynthesis
Epstein-Barr virus
Gene Expression Regulation, Viral
Herpesvirus 4, Human - genetics
Herpesvirus 4, Human - metabolism
Herpesvirus 4, Human - physiology
Humans
Molecular Biology
Nuclease Protection Assays
Promoter Regions, Genetic
Replication Origin
Reverse Transcriptase Polymerase Chain Reaction
RNA, Antisense - analysis
RNA, Messenger - biosynthesis
RNA, Messenger - chemistry
RNA, Viral - biosynthesis
RNA, Viral - chemistry
Transcription Initiation Site
Transcription, Genetic
Viral Proteins - biosynthesis
Viral Proteins - genetics
Virus Replication
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkm170