The Marek's Disease Virus Unique Gene MDV082 Is Dispensable for Virus Replication but Contributes to a Rapid Disease Onset

J Virol. 2021 Jul 12;95(15):e0013121. doi: 10.1128/JVI.00131-21. Epub 2021 Jul 12.

Abstract

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus of chickens that causes lymphomas in various organs. Most MDV genes are conserved among herpesviruses, while others are unique to MDV and may contribute to pathogenesis and/or tumor formation. High transcript levels of the MDV-specific genes MDV082, RLORF11, and SORF6 were recently detected in lytically infected cells; however, it remained elusive if the respective proteins are expressed and if they play a role in MDV pathogenesis. In this study, we first addressed if these proteins are expressed by inserting FLAG tags at their N or C termini. We could demonstrate that among the three genes tested, MDV082 is the only gene that encodes a protein and is expressed very late in MDV plaques in vitro. To investigate the role of this novel MDV082 protein in MDV pathogenesis, we generated a recombinant virus that lacks expression of the MDV082 protein. Our data revealed that the MDV082 protein contributes to the rapid onset of Marek's disease but is not essential for virus replication, spread, and tumor formation. Taken together, this study sheds light on the expression of MDV-specific genes and unravels the role of the late protein MDV082 in MDV pathogenesis. IMPORTANCE MDV is a highly oncogenic alphaherpesvirus that causes Marek's disease in chickens. The virus causes immense economic losses in the poultry industry due to the high morbidity and mortality, but also the cost of the vaccination. MDV encodes over 100 genes that are involved in various processes of the viral life cycle. Functional characterization of MDV genes is an essential step toward understanding the complex virus life cycle and MDV pathogenesis. Here, we have identified a novel protein encoded by MDV082 and two potential noncoding RNAs (RLORF11 and SORF6). The novel MDV082 protein is not needed for efficient MDV replication and tumor formation. However, our data demonstrate that the MDV082 protein is involved in the rapid onset of Marek's disease.

Keywords: MDV082; Marek’s disease virus; RLORF11; SORF6; expression kinetics; pathogenesis; tumorigenesis; unique genes; virus replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Viral / genetics*
  • Chickens / virology
  • Herpesvirus 2, Gallid / genetics*
  • Marek Disease / virology*
  • Poultry / virology
  • Viral Proteins / genetics*
  • Virus Replication / genetics

Substances

  • Viral Proteins