Poly(I)-poly(C) was reported to trigger MDA5 mediated IFN signaling in mammals [Kato H et al 2006; Gitlin L et al 2006]. Poly(I)-poly(C)-induced IFN production was inhibited in the presence of paramyxovirus V proteins both in human and in chicken cells. In addition, paramyxovirus V proteins were demonstrated to target helicase domain of MDA5, but not RIG-1 [Childs et al 2007, Childs et al 2009]. Furthermore, overexpression of chicken MDA5 has been shown to induce IFN promoter in chicken fibroblast cell line DF1, but not in human Vero cells. Similar to chicken MDA5, human MDA5 was unable to function in avian cells. Therefore, authors suggested that chicken MDA5 may function similar to its mammalian counterpart, but in a species-specific manner [Childs et al 2007].
Chicken MDA5 shares 60% overall sequence identity with human MDA5. Detailed analysis of human and chicken MDA5 revealed considerable sequence divergence between N-terminal effector CARD domains (43% amino acid identity), while the C-terminal helicase domains showed a relatively high degree of conservation (67% amino acid identity with extended regions of over 80%) [Childs et al 2007].