induced by interferons can also be overcome by the action of ICP0. This function of ICP0 also prevents production of RNase L, an enzyme that degrades single-stranded viral and cellular RNAs and induces host cell apoptosis in virus infected cells. Interaction with host cell SUMO-1 protein and disruption PML Nuclear Bodies Small ubiquitin-related modifier 1 (SUMO-1) is a protein produced by human cells that is involved in the modification of many proteins, including human PML protein. HSV-1 ICP0 and several of its homologs in other herpes viruses bind to SUMO-1 in a manner similar to endogenous proteins, causing depletion of SUMO-1, and disruption of nuclear bodies. Interaction with neuron-differentiating protein NRSF and protein cofactor coREST ICP0 interacts with a human protein, known as Neuronal Restrictive Silencer Factor (NRSF) or RE1-silencing transcription factor (REST) that regulates differences in gene expression between cells of neuronal or non-neuronal origin; NRSF is found in non-neuronal cells but not in fully differentiated neurons. This interaction is attributed to the partial similarity of ICP0 to the human protein CoREST, also called REST corepressor 1 (RCOR1), which combines with NRSF to repress expression of neuronal genes in non-neuronal cells. Although the full NRSF protein is not typically found in neurons, truncated forms of NRSF are produced that selectively control the expression of certain neurotransmitter channels in specialized neurons. Combination of ICP0 with these NRSF-like neuronal factors may silence herpes genes in neurons, blocking the production of other immediate-early genes such as ICP4 and reducing production of ICP22. The repressed production of immediate-early HSV genes may contribute to the establishment of latency during infection with herpes viruses. CoREST and NRSF combine with another cellular protein, histone deacetylase-1 (HDAC) to form a HDAC/CoREST/NRSF complex. This complex silences production of the HSV-1 protein ICP4 by interfering with chromatin remodeling of the viral DNA that is necessary to allow viral gene transcription; it deacetylates histones associated with viral DNA in viral chromatin. Furthermore, an NRSF-binding region is located between the viral genes expressing proteins ICP4 and ICP22. ICP0 interacts with coREST, dissociating HDAC1 from CoREST/NRSF in the HDAC/CoREST/NRSF complex and preventing the silencing of the HSV genome in non-neuronal cells. Suppression of ICP0 activity Interaction with latency-associated RNA transcript (LAT) During latent infection a viral RNA transcript inhibits expression of the herpes virus ICP0 gene via an antisense RNA mechanism. The RNA transcript is produced by the virus and accumulates in