The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

Nicholls, John M

Within the cell it has been found for a long time that influenza has evolved a strategy to evade the powerful IFN defence mechanism [73] but in 1998 Garcia-Sastre and colleagues showed that the production of recombinant influenza lacking a gene called non-structural protein (NS1) was able to suppress this IFN pathway [74] . NS1 employs this strategy at many levels, including targeting TRIM25. It will be remembered that TRIM25 is required to ubiqutinate and activate RIG-I leading to subsequent IFN production. For TRIM25 to perform this function it needs to be oligomerized and NS1 inhibition of this abolishes this activity. All influenza strains have this interaction with TRIM25, possibly because of the conserved Glu96 and Glu97 but the D92E change in H5N1 may affect function [75] . NS1 also functions to impair the interferon induced protein PKR which it will be recalled can shut down translation by sustained phosphorylation of the translation factor elF2α thus inhibiting virus propagation [76] .