Avian Influenza NS1 Proteins Inhibit Human, but Not Duck, RIG-I Ubiquitination and Interferon Signaling.

The nonstructural protein 1 (NS1) of influenza A viruses is an important virulence factor that controls host cell immune responses. In human cells, NS1 proteins inhibit the induction of type I interferon by several mechanisms, including potentially, by preventing the activation of the retinoic acid-inducible gene I (RIG-I) receptor by the ubiquitin ligase tripartite motif-containing protein 25 (TRIM25). It is unclear whether the inhibition of human TRIM25 is a universal function of all influenza A NS1 proteins or is strain dependent.

Influenza PB1-F2 Inhibits Avian MAVS Signaling.

RIG-I plays an essential role in the duck innate immune response to influenza infection. RIG-I engages the critical adaptor protein mitochondrial antiviral signaling (MAVS) to activate the downstream signaling pathway. The influenza A virus non-structural protein PB1-F2 interacts with MAVS in human cells to inhibit interferon production.

Extraintestinal manifestations of celiac disease: 33-mer gliadin binding to glutamate receptor GRINA as a new explanation.

We propose a biochemical mechanism for celiac disease and non-celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33-mer gliadin peptide and a component of the NMDA glutamate receptor ion channel - the human GRINA protein - using BLASTP software. Based on this homology the 33-mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners.

Duck TRIM27-L enhances MAVS signaling and is absent in chickens and turkeys.

Wild waterfowl, including mallard ducks, are the natural reservoir of avian influenza A virus and they are resistant to strains that would cause fatal infection in chickens. Here we investigate potential involvement of TRIM proteins in the differential response of ducks and chickens to influenza. We examine a cluster of TRIM genes located on a single scaffold in the duck genome, which is a conserved synteny group with a TRIM cluster located in the extended MHC region in chickens and turkeys.

Activation of duck RIG-I by TRIM25 is independent of anchored ubiquitin.

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains.

Defense genes missing from the flight division.

Birds have a smaller repertoire of immune genes than mammals. In our efforts to study antiviral responses to influenza in avian hosts, we have noted key genes that appear to be missing. As a result, we speculate that birds have impaired detection of viruses and intracellular pathogens.