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.

Genetic characterization of a Marek’s disease virus strain isolated in Japan

“…The deletion in MDV013/MDV013.5 was also found in some highly virulent strains [15]. However, this deletion does not seem to be correlated with increased virulence [48]. The Chinese and European strains showed a deletion in the same region of MDV056.…”

Marek’s disease viruses lacking either R-LORF10 or LORF4 have altered virulence in chickens

“…As mentioned previously, gL has been proposed as important factor to virus entry and cell-tocell spread via hetero-oligomeric complex formation with gH. However, there is an association between MDV virulence and naturally occurring gL mutation in MDV strains of varying virulence [26]. Furthermore, while not the primary goal of this study, the cell surface expression of MHC class II in CEF infected with mutant MDVs infected was monitored.…”

Evaluation of factors influencing the development of late Marek’s disease virus-induced immunosuppression: virus pathotype and host sex

“…Several studies have been conducted to identify molecular markers that could be used to pathotype MDVs and that will aid in understanding the molecular bases of MDV increased virulence (Lupiani et al, 2004;Shamblin et al, 2004;Santin et al, 2006;Spatz & Silva, 2007;Spatz et al, , 2008Tavlarides-Hontz et al, 2009;Spatz, 2010;Renz et al, 2012). However, specific virus-encoded factors of MDV-1 that contribute to enhanced virulence are still unclear.…”

“…Molecular changes in the oncogene meq have been shown to be associated with pathogenicity alteration of MDV-1, but they do not necessarily correlate with the already existing pathotyping system (Lupiani et al, 2004;Shamblin et al, 2004;Spatz & Silva, 2007;Spatz et al, , 2008Spatz, 2010;Renz et al, 2012). Changes in other regions such as glycoprotein L (Santin et al, 2006;Tavlarides-Hontz et al, 2009) and pp38 (Shamblin et al, 2004) have also been associated with increase in virulence, but the correlation with current classification in pathotypes remains elusive. Recently, Morgan et al (2008) reported differential expression of MDV-1 microRNA in MDVs, with higher expression of mdv1-miR-M4 and mdv1-miR-M2 in highly virulent MDVs than in less virulent MDVs.…”