We report the first sequence analysis of the entire complement of M-class genome segments of an avian reovirus (ARV). We analyzed the M1, M2 and M3 genome segment sequences, and sequences of the corresponding mu A, mu B and mu NS proteins, of two virus strains, ARV138 and ARV 176. The ARV M I genes were 2283 nucleotides in length and predicted to encode mu A proteins of 732 residues. Alignment of the homologous mammalian reovirus (MRV) mu 2 and ARV mu A proteins revealed a relatively low overall amino acid identity (similar to 30%), although several highly conserved regions were identified that may contribute to conserved Structural and/or functional properties of this minor core protein (i.e. the MRV mu 2 protein is an NTPase and a putative RNA-dependent RNA polyrnerase cofactor). The ARV M2 genes were 2158 nucleotides in length, encoding predicted mu B major outer capsid proteins of 676 amino acids, more than 30 amino acids shorter than the homologous MRV mu 1 proteins. In spite of the difference in size, the ARV/MRV mu B/mu 1 proteins were more conserved than any of the homologous proteins encoded by other M- or S-class genome segments, exhibiting percent amino acid identities of similar to 45%. The conserved regions included the residues involved in the maturation- and entry-specific proteoiytic cleavages that Occur in the MRV fit protein. Notably missing was a region recently implicated in MRV mu 1 stabilization and in forming "hub and spokes" complexes in the MRV Outer capsid. The ARV M3 genes were 1996 nucleotides in length and predicted to encode a mu NS non-structural protein of 635 amino acids, significantly shorter than the homologous MRV mu NS protein, which is attributed to several Substantial deletions in the aligned ARV mu NS proteins. Alignments of the ARV and MRV mu NS proteins revealed a low overall amino acid identity (similar to 25%), although several regions were relatively conserved. (c) 2005 Elsevier B.V. All rights reserved.