Marek’s Disease Virus (MDV) is a cell-associated alphaherpesvirus that infects chickens and is within the same subfamily as herpes simplex virus type 1 (HSV-1). HSV-1 has been shown to alter the mRNA landscape of the cell through the activity of the virion host shutoff (vhs) protein, a well-characterised endoribonuclease involved in degrading mRNA and leading to host translational shutoff. MDV expresses a homologue of vhs (vhsM), but its effect on the transcriptome has not been characterised before during infection. Because MDV is highly cell-associated, synchronous infection in vitro is difficult to achieve, and previous transcriptomic studies have been difficult to interpret due to the background of uninfected cells. To overcome this issue, we have used a GFP+ MDV strain to generate an MDV virus lacking the vhsM ORF (MDV-GFP-Δvhs) using CRISPR-Cas9 and have isolated GFP+ populations of WT and Δvhs MDV infected primary chicken embryo fibroblasts for subsequent RNA-sequencing. The results revealed that like HSV-1, MDV depletes the infected cell transcriptome. Nonetheless, this depletion is only modestly rescued in MDV-Δvhs infection, suggesting that vhs plays a more subtle role in MDV compared to HSV-1 infection, potentially targeting specific subsets of transcripts. To determine if vhsM plays a more obvious role in the chicken, we have recently performed an in vivo experiment with our MDV-Δvhs to investigate whether vhs functions differentially in tissue types such as peripheral blood mononuclear cells or feather follicle epithelium cells, the site of virus shedding. The results from these experiments will be presented.