Phenotypic Characterization of Recombinant Marek's Disease Virus in Live Birds Validates Polymorphisms Associated with Virulence.

Marek's disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact. 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.

A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants.

Background: The red junglefowl, the wild outgroup of domestic chickens, has historically served as a reference for genomic studies of domestic chickens. These studies have provided insight into the etiology of traits of commercial importance. However, the use of a single reference genome does not capture diversity present among modern breeds, many of which have accumulated molecular changes due to drift and selection.

Targeted Ablation of Exon 2 of the Avian Leukosis Virus-A (ALV-A) Receptor Gene in a Chicken Fibroblast Cell Line by CRISPR Abrogates ALV-A Infection.

The U.S. Department of Agriculture Avian Disease and Oncology Laboratory currently relies on live birds of specific genetic backgrounds for producing chicken-embryo fibroblasts that are used for the diagnosis and subtyping of field isolates associated with avian leukosis virus (ALV) outbreaks.

The immune cell landscape and response of Marek's disease resistant and susceptible chickens infected with Marek's disease virus.

Genetically resistant or susceptible chickens to Marek's disease (MD) have been widely used models to identify the molecular determinants of these phenotypes. However, these prior studies lacked the basic identification and understanding of immune cell types that could be translated toward improved MD control. To gain insights into specific immune cell types and their responses to Marek's disease virus (MDV) infection, we used single-cell RNA sequencing (scRNAseq) on splenic cells from MD resistant and susceptible birds.

Contribution of the TCRβ Repertoire to Marek's Disease Genetic Resistance in the Chicken.

Marek's disease (MD) is a lymphoproliferative disease of chickens induced by Marek's disease virus (MDV), an oncogenic α-herpesvirus. MDV has increased in virulence, prompting continued efforts in both improved vaccines and enhanced genetic resistance. Model pairs of genetically MD-resistant and MD-susceptible chickens that were either MHC-matched or MHC-congenic allowed characterization of T cell receptor (TCR) repertoires associated with MDV infection.

Fast-forwarding evolution-Accelerated adaptation in a proofreading-deficient hypermutator herpesvirus.

Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high-fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses.

Codon Deoptimization of UL54 in meq-Deleted Marek's Disease Vaccine Candidate Eliminates Lymphoid Atrophy but Reduces Vaccinal Protection.

Marek's disease (MD) is an oncogenic, lymphoproliferative, and highly contagious disease of chickens. Its etiologic agent is the alphaherpesvirus Marek's disease virus (MDV, Gallid alphaherpesvirus 2), and it is a chronic and ubiquitous problem for the poultry industry with significant economic impact in the United States and worldwide. We have previously demonstrated that MDV attenuated by dicodon deoptimization of the UL54 gene results in reduced gene product accumulation in vitro, with reduced viral genome copy number upon infection and reduced atrophy of bursa and thymus in vivo as well.

Attenuation of Marek's disease virus by codon pair deoptimization of a core gene.

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus of Gallus gallus, the domesticated chicken. Control strategies rely upon vaccination with live attenuated viruses of antigenically similar avian herpesviruses or attenuated strains of MDV. Recent studies in other viruses have shown that recoding certain viral genes to employ synonymous but rarely-used codon pairs resulted in viral attenuation.