Phenotypic Characterization of Recombinant Marek’s Disease Virus in Live Birds Validates Polymorphisms Associated with Virulence
Taejoong Kim,
Cari J. Hearn,
Jody Mays,
Deborah Velez-Irizarry,
Sanjay M. Reddy,
Stephen J. Spatz,
Hans H. Cheng,
John R. Dunn
Affiliations
Taejoong Kim
Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA
Cari J. Hearn
Avian Diseases and Oncology Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 4279 E. Mount Hope Road, East Lansing, MI 48823, USA
Jody Mays
Avian Diseases and Oncology Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 4279 E. Mount Hope Road, East Lansing, MI 48823, USA
Deborah Velez-Irizarry
Avian Diseases and Oncology Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 4279 E. Mount Hope Road, East Lansing, MI 48823, USA
Sanjay M. Reddy
Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA
Stephen J. Spatz
Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA
Hans H. Cheng
Avian Diseases and Oncology Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 4279 E. Mount Hope Road, East Lansing, MI 48823, USA
John R. Dunn
Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA
Marek’s disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact. Mardivirus gallidalpha 2, also known as Marek’s disease virus (MDV), is the causative pathogen and has been categorized based on its virulence rank into four pathotypes: mild (m), virulent (v), very virulent (vv), and very virulent plus (vv+). A prior comparative genomics study suggested that several single-nucleotide polymorphisms (SNPs) and genes in the MDV genome are associated with virulence, including nonsynonymous (ns) SNPs in eight open reading frames (ORF): UL22, UL36, UL37, UL41, UL43, R-LORF8, R-LORF7, and ICP4. To validate the contribution of these nsSNPs to virulence, the vv+MDV strain 686 genome was modified by replacing nucleotides with those observed in the vMDV strains. Pathogenicity studies indicated that these substitutions reduced the MD incidence and increased the survival of challenged birds. Furthermore, using the best-fit pathotyping method to rank the virulence, the modified vv+MDV 686 viruses resulted in a pathotype similar to the vvMDV Md5 strain. Thus, these results support our hypothesis that SNPs in one or more of these ORFs are associated with virulence but, as a group, are not sufficient to result in a vMDV pathotype, suggesting that there are additional variants in the MDV genome associated with virulence, which is not surprising given this complex phenotype and our previous finding of additional variants and SNPs associated with virulence.
