Protein modification with ISG15 blocks coxsackievirus pathology via antiviral and metabolic reprogramming
During early encounters between a pathogen and a cell, receptors located on the cell surface, in the cytosol or within endosomal (storage) compartments engage with the pathogen's nucleic acid (DNA/RNA) or pathogen-associated molecular patterns (PAMPs), as a host response to combat infection. The host response can initiate specific gene expression patterns and posttranscriptional (prior to translation of a gene into a protein product) control mechanisms at multiple levels and stages during disease development. The outcomes cause cells to produce type I interferons (IFNs) as a first line of defense to orchestrate a complex defense network in both infected and noninfected cells. As a classic example, the ubiquitin family protein IFN-stimulated gene of 15 kDa (known as ISG15) and its conjugation machinery including the enzyme Ube1L represents an IFN-induced broad spectrum antimicrobial system.