US3 Serine/Threonine Protein Kinase from MDV-1, MDV-2, and HVT Differentially Regulate Viral Gene Expression and Replication.

Yifei Liao,Sanjay M Reddy,Xin Fang,Mohammad Ai-Mahmood,Blanca Lupiani,Qinglei Li

doi:10.3390/microorganisms9040785

Abstract

Gallid alphaherpesvirus 2 (GaHV-2), commonly known as Marek’s disease virus type 1 (MDV-1), is an oncogenic avian alphaherpesvirus, and along with its close relatives—Gallid alphaherpesvirus 3 (GaHV-3) or MDV-2 and Meleagrid alphaherpesvirus 1 (MeHV-1) or turkey herpesvirus (HVT)—belongs to the Mardivirus genus. We and others previously showed that MDV-1 US3 protein kinase plays an important role in viral replication and pathogenesis, which could be partially compensated by MDV-2 and HVT US3. In this study, we further studied the differential roles of MDV-1, MDV-2 and HVT US3 in regulating viral gene expression and replication. Our results showed that MDV-2 and HVT US3 could differentially compensate MDV-1 US3 regulation of viral gene expression in vitro. MDV-2 and HVT US3 could also partially rescue the replication deficiency of MDV-1 US3 null virus in the spleen and thymus, as determined by immunohistochemistry analysis of MDV-1 pp38 protein. Importantly, using immunohistochemistry and dual immunofluorescence assays, we found that MDV-2 US3, but not HVT US3, fully compensated MDV-1 US3 regulation of MDV-1 replication in bursal B lymphocytes. In conclusion, our study provides the first comparative analysis of US3 from MDV-1, MDV-2 and HVT in regulating viral gene expression in cell culture and MDV-1 replication in lymphocytes.

Highlights

Marek’s disease (MD) is a lymphoproliferative disease of chickens, caused by an oncogenic avian alphaherepsvirus, Gallid alphaherpesvirus 2 [GaHV-2], commonly known asMarek’s disease virus type 1 (MDV-1)
Using chimeric MDVs (Figure 1), we recently reported that US 3 from MDV-2 and HVT, close relatives of MDV-1, could partially compensate the function of MDV-1 US 3 in virus replication and pathogenesis [17]
We further determined the role of MDV-1, MDV-2 and HVT US 3 in regulating viral gene expression in cell culture and virus replication in lymphoid organs

Summary

Introduction

Marek’s disease (MD) is a lymphoproliferative disease of chickens, caused by an oncogenic avian alphaherepsvirus, Gallid alphaherpesvirus 2 [GaHV-2], commonly known asMarek’s disease virus type 1 (MDV-1). We further determined the role of MDV-1, MDV-2 and HVT US 3 in regulating viral gene expression in cell culture and virus replication in lymphoid organs.

Results

Conclusion