Uncovering viral inhibitory mechanisms of interferon poduction and signaling
OA Version
Citation
Abstract
Viruses pose a major threat to human health. In response, the human immune system has evolved various methods to combat viral infections. During viral infection, the innate immune system recognizes and counteracts foreign pathogens by inducing an antiviral response that involves the production of type I interferons (IFNs), such as IFNꞵ, which promote transcription of hundreds of interferon-stimulated genes (ISGs), responsible for inhibiting viral replication and infection. ISGs are activated through an upstream IFN-stimulated response element (ISRE) promoter sequence. Viruses have thus adapted multiple mechanisms to evade immune detection, encoding proteins and peptides that inhibit the production of IFNs and subsequent activation of ISGs. However, knowledge of viral peptides interfering with the interferon signaling pathway is limited to a few anecdotal examples. Here, we will use a stable cell line carrying the GFP reporter under control of the IFNꞵ or ISRE promoter and a viral peptide library comprising ~70,000 peptides from more than 20 viruses that infect humans to perform a pooled screen. This will allow the identification of viral peptides that interfere with activation of the IFNꞵ and ISRE promoter and subsequently inhibit IFNꞵ and ISG expression. Overall, the identification and characterization of inhibitory viral peptides of the interferon signaling pathway will advance the understanding of viral strategies of immune evasion and offer insight into potential therapeutic avenues for combating viral diseases.