Influenza A NS1 Helps Prevents Innate Immunity via Inhibition of TRIM25

Abstract

One of the key components to vertebrate survival is the innate ability to produce interferons (IFN). Type 1 IFN are regulatory proteins expressed in response to infection caused by invading viruses. The synthesis of these cytokines is upregulated through several different cellular pathways. For instance, the RIG‐I pathway detects foreign viral RNA enabling the CARD domains of RIG‐I to be ubiquitinized by the enzyme, TRIM25. This initiates a signaling cascade which ultimately results in the expression of IFN. Once produced, IFN are released from the infected cell and bind to IFN‐alpha/beta receptors on the epithelial cells of the respiratory system. This consequently produces antiviral cytokines which degrade viral RNA. In defense to this mechanism, Influenza A virus carries an NS1 gene that has been shown to compromise the regulation of IFN. NS1 binds to TRIM25, preventing the enzyme from ubiquitinating RIG‐I and ultimately inhibiting cytokine production. NS1, although not necessary for construction of the virus itself, compromises the innate immune system, resulting in the flu. The E.E. Waddell SMART Team (Students Modeling A Research Topic), in collaboration with MSOE, has built accurate models of IFN and NS1 using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.