Marek’s disease virus-1 (MDV-1) is a cell-associated alphaherpesvirus that infects chickens and

belongs to the same subfamily as herpes simplex virus type 1 (HSV-1). HSV-1 has been shown to

extensively remodel the mRNA landscape of the cell, largely attributed through the activity of the

virion host shutoff (vhs) protein, a well-known endoribonuclease involved in degrading mRNA and

leading to host translational shutoff.

Due to its strictly cell-associated nature, transcriptomic studies with MDV-1 can be challenging

as not all cells within the monolayer become infected. To overcome this limitation, a GFP+ virus

was used as a marker of infection to investigate the transcriptomic changes during in vitro

infection of primary chicken embryo fibroblast (CEF) cells. This revealed that MDV-1 alters the

global transcriptome in response to infection.

MDV-1 expresses a homologue of vhs (vhsM). To better understand its activity, vhsM was

ectopically expressed in both HeLa cells and the chicken DF1 fibroblast cell line. The studies

demonstrated that vhsM activity is influenced by the host cell context and highlighted that the

outputs of vhs activity may be mechanistically separable.

However, the activity of viral proteins may be influenced by other viral factors, highlighting the

importance of studying their function during infection. Therefore, infection-based studies were

performed in primary CEF cells using a ΔvhsM virus generated by CRISPR-Cas9. Nonetheless,

deletion of vhsM only had a subtle effect during MDV-1 infection of primary CEF cells. As

fibroblast cells are not primary target cells for MDV-1 in vivo, an animal study was subsequently

performed to investigate whether vhsM functions differently in tissue types such as peripheral

blood mononuclear cells (PBMCs) and feathers. These studies suggested that vhsM may

contribute to the progression of infection within the natural host.