Herpes simplex virus (HSV) is a double-stranded DNA virus that participates in the development of various diseases. The development of HSV-1 infection is influenced by numerous host or cell factors (so-called virulence factors), among which is the ADAR1 protein. ADAR1 is one of the main enzymes that edit RNA and regulate numerous defense mechanisms of the cell, including the modulation of protein kinase R (PKR) activation. Activation of PKR can lead to block of protein synthesis and thereby prevent efficient viral replication. In addition to host proteins, a number of viral nonstructural proteins, such as ICP34.5, a major neurovirulence factor, inhibit signaling pathways that overlap with ADAR1 regulation, including host defense PKR. Using the methods of transfection, Western Blot analysis and titration, our research showed that in cells with reduced or terminated expression of ADAR1, activation of PKR occurs after HSV-1 infection, regardless of the presence of ICP34.5, a viral inhibitor of the same signaling pathways. These results suggest that in the absence of ADAR1, the PKR activation signal is too strong and that ICP34.5 has no inhibitory capacity or activation occurs before significant ICP34.5 expression. Our hypothesis is that inhibition of activated PKR-mediated shutoff of protein synthesis will lead to enhanced viral replication in ADAR1-deficient cells. In the next part of the experiment, we successfully confirmed the proviral role of the enzyme ADAR1 and the subsequently added molecule ISRIB. ISRIB is a pharmacological inhibitor that binds to eIF2β and thereby supresses the activation of eIF2α and enables further protein synthesis. Our research confirmed our hypothesis, i.e. treatment of cells with ISRIB led to enhanced virus replication in ADAR1 KO cells. However, to our surprise, we discovered that the addition of ISRIB in HSV-1 infection also results in reduced activation of the PKR kinase. These results suggest a potential regulatory feedback mechanism, however the exact mechanism remains to be confirmed.