Defense genes missing from the flight division

Abstract

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. Birds are missing TLR8, a detector for single-stranded RNA. Chickens also lack RIG-I, the intracellular detector for single-stranded viral RNA. Riplet, an activator for RIG-I, is also missing in chickens. IRF3, the nuclear activator of interferon-beta in the RIG-I pathway is missing in birds. Downstream of interferon (IFN) signaling, some of the antiviral effectors are missing, including ISG15, and ISG54 and ISG56 (IFITs). Birds have only three antibody isotypes and IgD is missing. Ducks, but not chickens, make an unusual truncated IgY antibody that is missing the Fc fragment. Chickens have an expanded family of LILR leukocyte receptor genes, called CHIR genes, with hundreds of members, including several that encode IgY Fc receptors. Intriguingly, LILR homologues appear to be missing in ducks, including these IgY Fc receptors. The truncated IgY in ducks, and the duplicated IgY receptor genes in chickens may both have resulted from selective pressure by a pathogen on IgY FcR interactions. Birds have a minimal MHC, and the TAP transport and presentation of peptides on MHC class I is constrained, limiting function. Perhaps removing some constraint, ducks appear to lack tapasin, a chaperone involved in loading peptides on MHC class I. Finally, the absence of lymphotoxin-alpha and beta may account for the observed lack of lymph nodes in birds. As illustrated by these examples, the picture that emerges is some impairment of immune response to viruses in birds, either a cause or consequence of the host-pathogen arms race and long evolutionary relationship of birds and RNA viruses.

Keywords: Chicken; Duck; Lymph node; Major Histocompatibility Complex; RIG-I; TLR8; pathway.

Fig. 1

A simplified schematic of the RIG-I signaling pathway. RIG-I detects 5′ triphosphate RNA and undergoes conformational changes that allow it to engage MAVS on the mitochondrion. TRIM25 and Riplet/RNF135 are E3 ubiquitin ligases involved in activation of RIG-I. MAVS multimerization initiates a signaling cascade that ultimately results in dimerization and translocation of IRF3 or IRF7, along with NFkB into the nucleus to activate IFNβ. Type I IFNs acting on neighboring cells turn on downstream interferon stimulated genes including MX, IFIT, ISG15 and many others. This figure is adapted from Bowie and Unterholtzner (2008).

Fig. 2

A phylogenetic tree showing similarity of avian and mammalian IFIT sequences. Sequences were aligned and phylogenetic tree generated using a maximum likelihood estimation using a program called PhyML using www.phylogeny.fr. (Dereeper et al., 2008). Accession numbers for the IFIT sequences were: chicken IFIT5 (XM_421662.3), turkey IFIT5 (XM_003208028.1), zebra finch IFIT5 (XM_002188552.1), human IFIT1 (NM_001270927.1), mouse IFIT1(NM_008331.3), human IFIT2 (NM_001547.4), mouse IFIT2 (NM_008332.3), human IFIT3 (NM_001031683.2), mouse IFIT3 (NM_010501.2), human IFIT5 (NM_012420.2). Note the duck IFIT sequence is a partial sequence.