Accumulation of attenuating mutations in varying proportions within a high passage very virulent plus strain of Gallid herpesvirus type 2
Abstract
Marek's disease (MD) is controlled through mass vaccination. Although these vaccines reduce or delay tumor formation they fail to induce sterilizing immunity and prevent virus shedding. Relatively little is known about the genetic changes that lead to attenuation. It has been established that serial passage of virulent strains in avian cell lines results in the generation of attenuated progeny at some undefined passage level. A detailed cataloging of the mutations needed for attenuation will be important for advancing our understanding of MD biology and should facilitate the development of better vaccines. Using deep sequencing, the complete nucleotide sequence of the very virulent plus (vv+) strain 648A representing the 101 st passage was determined. Pathotyping studies have indicated that 648Ap101 is indeed attenuated. Comparative sequence analysis with the 648A strain at passage 11 has identified numerous gross genetic changes and subtle single nucleotide polymorphisms scattered throughout the genome. Relative to the strain (648Ap11), deletions were identified in MD-specific genes located in the repeat long (R(L)), unique long (U(L)) and repeat short (R(S)) regions. A deletion in the R(L) region, present in 33% of the p101 s...Continue Reading
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