title: Examination of the effect of a naturally occurring mutation in glycoprotein L on Marek's disease virus pathogenesis.
abstract: We recently reported a comparison of glycoprotein-encoding genes of different Marek's disease virus pathotypes (MDVs). One mutation found predominantly in very virulent (vv)+MDVs was a 12-bp (four-amino acid) deletion in the glycoprotein L (gL)-encoding gene in four of 23 MDV strains examined (three were vv+MDVs and one was a vvMDV). This mutation was noted in the gL of the TK (615K) strain, but not in the RL (615J) strain of MDV. These strains have identical mutations in the meq gene characteristic of vv+MDVs but can be distinguished by the mutation in the gL-encoding gene. The TK strain was originally isolated from vaccinated chickens and appeared to confer or enhance horizontal transmission of the vaccine virus, herpesvirus of turkeys (HVT). Because the molecular basis for increased virulence of MDV field strains is unknown, we hypothesized that one mechanism might be by coreplication of MDV-1 strains with HVT and that it could be mediated by the mutation of gL, an essential component of the glycoprotein H/L complex. In this study, we compared the pathogenicity of TK (615K) and RL (615J) strains of MDV in the presence and absence of simultaneous HVT coinfection. MDV infections were monitored at the levels of viremia (for both MDV-1 and HVT), clinical signs of MD, tumor incidence, and mortality in 1) inoculated chickens, 2) chickens exposed at 1 day of age, 3) chickens exposed at 2 wk of age, and 4) chickens exposed to both TK/HVT- and RL/HVT-infected chickens at 6 wk of age. We found high incidences of clinical MD signs in all inoculated treatment groups and all chickens exposed to TK and RL viruses, regardless of the presence of HVT. The median time to death of chickens exposed to TK1HVT-infected chickens, however, was lower than the other treatment groups for contact-exposed chickens. Although this difference was not considered to be statistically significant to a rigorously interpreted degree because of the removal of chickens for sampling from the test groups, these data suggest that replication of the TK strain and HVT, when coadministered, might incrementally affect the virulence of MDV-1 strains. The strict correlation of this enhancement of virulence with the mutation in gL, however, requires additional experiments with genetically identical MDV background strains.
authors.affiliation: Departamento de Medicina Veterinária, Setor de Ciências Agrárias, UFPR, Curitiba-Pr, Brazil.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Santin
authors.forename: Christine E
authors.initials: CE
authors.lastname: Shamblin
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Prigge
authors.forename: Vaithilingaraja
authors.initials: V
authors.lastname: Arumugaswami
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dienglewicz
authors.forename: Mark S
authors.initials: MS
authors.lastname: Parcells
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002645:Chickens / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D001352:Herpesvirus 1, Gallid / Q000235:genetics* / Q000472:pathogenicity*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008380:Marek Disease / Q000401:mortality / Q000635:transmission / Q000821:virology*; D009154:Mutation / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics*; D014766:Viremia; D014774:Virulence; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; C089459:glycoprotein L, Marek's disease virus