Amino acid identity between NS4 of the different Orbivirus species compared ranged from 5% to 50%. Highest identity was detected between BTV and EHDV (50%), followed by PHSV and YUOV-1 (30%). Amino acid identity in NS4 between the tickborne and insect-borne viruses, ranged between 5% to 18% (table 2). Local blast analyses using BLAST-P or TBLAST-N identified significant matches (as defined by the E value in BLAST) between NS4 proteins encoded by other orbiviruses. Analysis of NS4 protein sequences using the pfam program, which uses the hidden Markov model (HMM) based profiles to identify or predict protein functionalities [31, 32] , revealed strong similarities to certain conserved functional motifs. AHSV NS4 exhibits strong relatedness over almost its entire length with DUF domains that have helical structures known to be involved in nucleic acid binding and/or modification [33] . Previous analysis of GIV NS4 identified a 72 amino acid fragment (aa 82 to 153) with 39% similarity to dsRNA-binding domains of similar length (approximately 68aa) in other reovirus proteins [ [18] or other dsRNA binding proteins [34] . BTV NS4 (77aa long) also exhibits relatedness (over aa 14-54) to a DUF domain, belonging to the MetJ/Arc repressor superfamily [35] , which has a ribbon-ribbonhelix-helix DNA-binding motif, with the beta-ribbon located in and recognising the major groove of operator DNA.