Key result
Md5B40BAC-derived viruses showed better replication in vivo and higher virulence, while mixing homogeneous virulent MDV with avirulent virus noticeably compromised overall virulence.
The generation of virulent MDV from BAC clones demonstrates that viral population complexity is important in MDV pathogenesis.
Supports viral population complexity as key to MDV virulence in animals; hypothesis-generating for broader herpesvirus pathogenesis research.
Genetic homogeneity of a test population is essential to precisely associate a viral genome sequence and its phenotype at the nucleotide level. However, homogeneity is not easy to achieve for Marek's disease virus (MDV) due to its strictly cell-associated replication. To address this problem, two virulent infectious bacterial artificial chromosome (BAC) clones of MDV were generated from an MDV genome previously cloned as five overlapping cosmids. The Md5SN5BAC clone has the BAC vector inserted between the 3' ends of UL3 and UL4, such that no known ORFs should be disrupted. The BAC vector is flanked by loxP sites, so that it can be deleted from the viral genome by transfecting Md5SN5BAC into a newly developed chicken cell line that constitutively expresses Cre recombinase. The Md5B40BAC clone has the BAC vector replacing a portion of US2, a location similar to that used by other groups to construct MDV-BAC clones. Although both BACs were capable of producing infectious virulent MDV when inoculated into susceptible chickens, Md5B40BAC-derived viruses showed somewhat better replication in vivo and higher virulence. Removal of the BAC vector in Md5SN5BAC-derived viruses had no influence on virulence. Interestingly, when genetically homogeneous virulent MDV generated from Md5B40BAC was mixed with avirulent virus, the overall virulence of the mixed population was noticeably compromised, which emphasizes the importance of MDV population complexity in pathogenesis.
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Niikura et al. (2010) studied Marek's disease virus (MDV). Md5SN5BAC and Md5B40BAC clones vs. Avirulent virus was evaluated on Viral replication and virulence in susceptible chickens. Md5B40BAC-derived viruses showed better replication in vivo and higher virulence, while mixing homogeneous virulent MDV with avirulent virus noticeably compromised overall virulence.
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