ARS | Publication request: Uncovering the genetic basis of attenuation in Marek’s disease virus

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: June 24, 2012
Publication Date: June 24, 2012
Citation: Hildebrandt, E., Niikura, M., Cheng, H.H. 2012. Uncovering the genetic basis of attenuation in Marek’s disease virus [abstract]. 9th International Symposium on Marek's Disease and Avian Herpesviruses, June 24-28, 2012, Freie Universitat Berlin. p.23.

Technical Abstract: While in vitro serial passage of Marek’s disease virus (MDV) is a proven method to attenuate MDV strains, the underlying genetic changes responsible for attenuation remains unknown. To identify candidate genes and mutations, a virulent MDV generated from an Md5-containing BAC clone was serially passed in triplicate to create replicate attenuated strains. Whole genome and transcriptome sequencing of the attenuated viral populations was conducted to identify changes in DNA and RNA compared to the virulent, parental virus. Candidate mutations identified in the attenuated replicates were then tracked via targeted resequencing to determine their emergence and spread in the viral population at 10 serial passage intervals. Creation of recombinant viruses containing candidate mutations in an otherwise virulent MDV BAC background is currently underway in order to determine the extent in which the attenuated mutations affect MDV virulence. One especially noteworthy candidate gene identified is ICP4 as all attenuated replicates contained multiple nonsynonymous mutations. Several of these mutations occurred at high frequencies >50%, including one SNP that become completely fixed in one attenuated replicate, suggesting ICP4 likely plays an important role in attenuation.