Interferons and Antiviral Action

Viruses and their hosts have evolved to coexist by maintaining viral homeostasis. At the organism level, the immune system of the host plays a major role in clearing the infection or driving the viruses to enter a latent phase. In addition to the direct action of the cells of the immune system, various cytokines, most importantly the interferons (IFNs) system, produced by them are critically important in this process. The majority of the interferon-stimulated genes (ISGs) that are induced by IFN, double-stranded RNA (dsRNA), and viruses contain IFN-stimulated response elements (ISREs) in their promoters. The usual mechanism calls for inhibition of several steps of viral gene expression through the actions of several ISG products. ISG-encoded proteins have been chosen because of the diversity of their functions and their perceived importance in mediating antiviral actions. Protein kinase RNA regulated (PKR) was one of the earliest antiviral ISGs identified and is one of the most thoroughly investigated to date. PKR has been implicated in regulation of apoptosis both in the presence and absence of viral infection. The importance of PKR in mediating antiviral actions of IFN is manifested by the variety of strategies used by different viruses to evade PKR’s activation or action. The common structural features of adenosine deaminase acting on RNA (ADAR) family proteins include a dsRNA-binding domain and a conserved cytidine deaminase domain at the carboxyl terminus that contains highly conserved residues thought to be involved in catalysis.