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

Abstract

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. We note a TRIM27-like gene is present in ducks, and absent in chickens and turkeys. Orthologous genes are predicted in many birds and reptiles, suggesting the gene has been lost in chickens and turkeys. Using quantitative real-time PCR (qPCR) we show that TRIM27-L, and the related TRIM27.1, are upregulated 5- and 9-fold at 1 day post-infection with highly pathogenic A/Vietnam/1203/2004. To assess whether TRIM27.1 or TRIM27-L are involved in modulation of antiviral gene expression, we overexpressed them in DF1 chicken cells, and neither show any direct effect on innate immune gene expression. However, when co-transfected with duck RIG-I-N (d2CARD) to constitutively activate the MAVS pathway, TRIM27.1 weakly decreases, while TRIM27-L strongly activates innate immune signalling leading to increased transcription of antiviral genes MX1 and IFN-β. Furthermore, when both are co-expressed, the activation of the MAVS signalling pathway by TRIM27-L over-rides the inhibition by TRIM27.1. Thus ducks have an activating TRIM27-L to augment MAVS signalling following RIG-I detection, while chickens lack both TRIM27-L and RIG-I itself.

The TRIMendous Role of TRIMs in Virus–Host Interactions

“…Expression of chicken TRIM25 is induced after Newcastle disease virus (NDV), poly(I:C) treatment, or poly(dA:dT) treatment [ 101 ], probably via a type-I IFN signaling-dependent pathway. Similar to human TRIM25, TRIM27-L stimulates IFN-β production in response to IAV infection in ducks [ 102 ]. This anti-viral benefit is absent in chickens and turkeys, as they do not carry the TRIM27-L gene in their TRIM cluster [ 102 ].…”

“…Similar to human TRIM25, TRIM27-L stimulates IFN-β production in response to IAV infection in ducks [ 102 ]. This anti-viral benefit is absent in chickens and turkeys, as they do not carry the TRIM27-L gene in their TRIM cluster [ 102 ]. However, expression of duck TRIM27-L and d2CARD in chicken DF1 cell lines was shown to facilitate IFN-β and MX1 expression [ 102 ].…”

“…This anti-viral benefit is absent in chickens and turkeys, as they do not carry the TRIM27-L gene in their TRIM cluster [ 102 ]. However, expression of duck TRIM27-L and d2CARD in chicken DF1 cell lines was shown to facilitate IFN-β and MX1 expression [ 102 ]. This difference may account for the different pathologies in avian species as waterfowl are typically more resistant to some strains of IAV as compared to chickens.…”

Influenza PB1-F2 Inhibits Avian MAVS Signaling

“…The average Pearsons's R value of 0.67 indicated moderate co-localization ( Figure 4D). PB1-F2 co-immunoprecipitated with V5-MAVS, but not with another V5-tagged duck protein, the PRY/SPRY domain fragment of duck TRIM27-L [51], suggesting a specific interaction ( Figure 4E).…”

“…That RIG-I CARD domains induce interferon through functional MAVS interactions is demonstrated by the fact that duck RIG-I CARD domains (GST-d2CARD), but not human RIG-I CARD domains (GST-h2CARD), stimulated the IFN-β promoter in chicken cells, while GST-h2CARD was active in human HEK293T cells ( Figure 2G and H). It is known that the RIG-I-MAVS interacting surfaces are sufficiently diverged between humans and ducks that they do not interact cross-species [51]. The MAVS-CARD-RIG-I-CARD interface is poorly conserved between humans and ducks, but the overall structure is conserved such that the tandem T175K/T176E mutations on duck RIG-I permit interaction with human MAVS in HEK293T cells [7].…”