Pattern Recognition Receptor Signaling and Innate Responses to Influenza A Viruses in the Mallard Duck, Compared to Humans and Chickens

Abstract

Mallard ducks are a natural host and reservoir of avian Influenza A viruses. While most influenza strains can replicate in mallards, the virus typically does not cause substantial disease in this host. Mallards are often resistant to disease caused by highly pathogenic avian influenza viruses, while the same strains can cause severe infection in humans, chickens, and even other species of ducks, resulting in systemic spread of the virus and even death. The differences in influenza detection and antiviral effectors responsible for limiting damage in the mallards are largely unknown. Domestic mallards have an early and robust innate response to infection that seems to limit replication and clear highly pathogenic strains. The regulation and timing of the response to influenza also seems to circumvent damage done by a prolonged or dysregulated immune response. Rapid initiation of innate immune responses depends on viral recognition by pattern recognition receptors (PRRs) expressed in tissues where the virus replicates. RIG-like receptors (RLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) are all important influenza sensors in mammals during infection. Ducks utilize many of the same PRRs to detect influenza, namely RIG-I, TLR7, and TLR3 and their downstream adaptors. Ducks also express many of the same signal transduction proteins including TBK1, TRIF, and TRAF3. Some antiviral effectors expressed downstream of these signaling pathways inhibit influenza replication in ducks. In this review, we summarize the recent advances in our understanding of influenza recognition and response through duck PRRs and their adaptors. We compare basal tissue expression and regulation of these signaling components in birds, to better understand what contributes to influenza resistance in the duck.

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

“…In particular, changes in the phosphorylation levels of NF-κB, as well as MyD88, receptor interacting protein 1 (RIP1), MDA5, and IRF7, indicated an important role of protein phosphorylation in duck immune responses to viral antigens [ 329 ]. Pattern recognition receptor signaling during innate responses to influenza A viruses in the mallard duck was recently reviewed [ 330 ], and the fundamental roles of NF-κB in innate immune responses to duck Tembusu virus infection were discussed in detail [ 331 ].…”

Differential gene expression reveals host factors for viral shedding variation in mallards (Anas platyrhynchos) infected with low-pathogenic avian influenza virus

“…High shedders (H) were the top 20% of birds with the highest cloacal virus titer, moderate shedders (M) were the top half of the lowest 80% of virus titers, and low shedders (L) were the bottom half of the lowest 80% of virus titers in each group. To detect differential gene expression related to active viral shedding during the innate immune response (48,49), only the virus titer collected on the day the bird was sacrificed was used to categorize shed level groups in early-stage infection (groups I1 and I2). To detect differential gene expression related to the adaptive immune response (35,61), cloacal virus titers on one to five DPI were averaged to create a cumulative virus titer for late-stage infection (group I5).…”

“…These ISGs are specifically important for antiviral defense because they participate in various protective mechanisms that inhibit viral replication and regulate the interferon pathway (Table 2 and Table 3). ISG production is dependent upon a series of biochemical cascades beginning with PRRs recognizing intracellular virus which triggers the transcription of type I and II interferons (31,32,48), thus it is likely that intracellular virus is responsible for the interferon response. Although shed level groups were not characterized using intracellular virus titers, cloacal virus titers are known to be positively correlated with virus titers in ileum and bursa tissue (22); therefore, it is likely that high shedders also have high viral replication in these tissues.…”

“…We hypothesized that gene expression in the ileum and bursa would be associated with intraspecific viral shedding variation in LPAIV-infected mallards because LPAIV primarily replicates in the epithelial cells of both the intestines and bursa of Fabricius (hereafter referred to as "bursa") of waterfowl by gaining entry via sialic acid receptors (44)(45)(46)(47). Further, the antiviral immune response occurs at the site of replication (31,48,49); therefore, we predicted that gene expression would differ: 1) between infected and uninfected birds, 2) between days postinfection, with innate immunity genes expressed early in the infection and adaptive immunity genes expressed later in the infection, 3) between bird groups with various viral shedding levels, and 4) that viral shedding magnitude would be correlated with the expression level of genes involved in cell entry and the immune response. We tested our hypotheses by evaluating gene expression at various time points post-infection to detect differential gene expression with respect to infection stage, infection site, and viral shedding in an important reservoir host for AIV, the mallard (50)(51)(52)(53).…”

Chicken miR-126-5p Negatively Regulates Antiviral Innate Immunity By Targeting TRAF3

“…RNA viruses such as influenza A virus (IAV), Avian influenza virus (AIV) and Newcastle disease virus (NDV) cause serious diseases in humans and animals, especially chickens, which have a high mortality rate after infection 3 . TRLs, RLRs and NLRs are the three important influenza virus PRRs for the host.…”