In the current study, our aim was to unravel host factors that drive neuronal damage during HSV‐1 infection that may be priming the molecular landscape of the central nervous system towards disease processes such as demyelinating disorders and in that regard show the disruption of the MLKL‒OPTN axis in driving widespread demyelination resulting in behavioural and functional deficits in our animal model. This evidence concerns the gene MLKL and demyelinating disease.