Marek's disease virus reactivation from latency: changes in gene expression at the origin of replication.
Marek's disease is a contagious lymphoma of chickens caused by Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes latency within and transforms chicken CD4+ T-cells. Transformed T-cells are seen as skin leukosis or as lymphomas in visceral organs. A major focus of our laboratory is the functional study of genes flanking the origin of replication. This origin (OriLyt) is contained within the repeats flanking the unique long (UL) region of the genome (IRL and TRL). To the left of this Ori are genes associated with MDV latent/transforming infection [1.8-kb RNA family, pp14, Meq), and to the right (UL) are genes associated with early stages of MDV lytic infection [BamHI-H-encoded protein (Hep), pp38/pp24, Mys]. During latency, MDV suppresses lytic gene expression and has evolved mechanisms for blocking the apoptosis of latently-infected CD4+ T-cells. Of the genes expressed during MDV latency and in the transformed cell, the Meq (Marek's EcoRI-Q-encoded protein) has been shown to block apoptosis and transactivate gene expression. Upon reactivation to lytic infection, we have found that splice variants of Meq predominate and that these forms lack several of the domains important to Meq trans-activation and trans-repression. We have found that rightward from the origin of replication, a family genes, including phosphoprotein 38 (pp38) are expressed during early stages of reactivation. Three separate open reading frames (Hep, Mys, and pp38) are encoded by distinct transcripts from this region. We are now determining the kinetics of expression of these transcripts and their relative abundance during reactivation.
Parcells
M S
MS
Department of Poultry Science, University of Arkansas, Fayetteville, Arkansas 72701, USA. parcells@uark.edu
Arumugaswami
V
V
Prigge
J T
JT
Pandya
K
K
Dienglewicz
R L
RL
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D005786:Gene Expression Regulation; D016209:Interleukin-8 / Q000235:genetics; D007700:Kinetics; D025922:Mardivirus / Q000235:genetics* / Q000472:pathogenicity*; D008380:Marek Disease; D010750:Phosphoproteins / Q000235:genetics; D011200:Poultry; D011201:Poultry Diseases / Q000235:genetics* / Q000821:virology*; D014158:Transcription, Genetic; D014779:Virus Replication
D016209:Interleukin-8; D010750:Phosphoproteins