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Self-excision of the BAC sequences from the recombinant Marek's disease virus genome increases replication and pathogenicity

Abstract:
Abstract Cloning of full length genomes of herpesviruses as bacterial artificial chromosomes (BAC) has greatly facilitated the manipulation of the genomes of several herpesviruses to identify the pathogenic determinants. We have previously reported the construction of the BAC clone (pRB-1B5) of the highly oncogenic Marek's disease virus (MDV) strain RB-1B, which has proven to be a valuable resource for elucidating several oncogenic determinants. Despite the retention of the BAC replicon within the genome, the reconstituted virus was able to induce tumours in susceptible chickens. Nevertheless, it was unclear whether the presence of the BAC influenced the full oncogenic potential of the reconstituted virus. To maximize the closeness of BAC-derived virus to the parental RB-1B strain, we modified the existing pRB-1B5 clone by restoring the Us2 and by introducing SV40-cre cassette within the loxP sites of the mini-F plasmid, to allow self-excision of the plasmid sequences in chicken cells. The reconstituted virus from the modified clone showed significant improvement in replication in vitro and in vivo. Excision of the BAC sequences also enhanced the pathogenicity to levels similar to that of the parental virus, as the cumulative incidence of Marek's disease in groups infected with the recombinant and the parental viruses showed no significant differences. Thus, we have been able to make significant improvements to the existing BAC clone of this highly oncogenic virus which would certainly increase its usefulness as a valuable tool for studies on identifying the oncogenic determinants of this major avian pathogen.
Publication status:
Published
Peer review status:
Peer reviewed

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Role:
Author
ORCID:
0000-0001-8916-8552
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Institution:
University of Oxford
Role:
Author
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Role:
Author
ORCID:
0000-0001-6766-6315
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0002-8255-516X


Publisher:
BioMed Central
Journal:
Virology Journal More from this journal
Volume:
5
Issue:
1
Pages:
19-19
Publication date:
2008-01-30
DOI:
EISSN:
1743-422X
ISSN:
1743-422X


Language:
English
Keywords:
Pubs id:
627282
Local pid:
pubs:627282
Source identifiers:
W2059503503
Deposit date:
2026-05-23
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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