Seminar

Molecular insights and therapeutic use of IFN-B induction pathway as antiviral treatment

Estanislao Nistal Villán, PhD

Detection of pathogens by cells is a key event of defense against infections. RIG-I like receptors (RLRs) detect specific RNAs produced by virus replication and activate a signaling cascade that results in the production of interferon beta (IFN-β) as well as several other antiviral and proinflammatory cytokines. We have been working for some time in understanding the mechanisms involved in the activation and repression of RLRs as well as its manipulation. Conventional type I IFN antiviral treatments are based on administration of recombinant purified protein or administration of different vectors that can produce type I IFN. Despite its proven antiviral and antitumoral effects, many individuals do not respond to administration of such therapies. We have developed adeno-associated virus (AAV) vectors expressing different elements of the RLR dependent pathway. Some constructs lead to an efficient IFN-β induction in a broad spectrum of cells from different species. Those vectors have been tested for their ability to induce IFN-β, creating an antiviral state in different in vitro and in vivo models, even in a scenario that is not responding to recombinant IFN-β. Some of AAV vectors can synergize with the host immune system and combat viral infections. We propose the use of our strategy as an alternative to malignancies that are refractory to such type I IFN treatment like some IFN-treated resistant chronic viral infections.