It was suggested that translation of ORFx may be initiated via 'leaky ribosome-scanning' [17] , although the presence of additional AUG codons between the VP6 initiation codon and the presumed NS4 initiation codon in some orbiviruses (including BTV) suggests that additional mechanisms for bypassing intervening AUG codons may be operating [17] . An A-rich polypurine tract is present upstream of the NS4 ORF in all of the sequenced Orbivirus species, except the tick borne St. Croix River virus (SCRV, [46] . The SCRV NS4-ORF (nt 101-379) is interrupted by a stop codon at position 217. Although hydrophobicity profiles of putative NS4 proteins from BTV, AHSV, PHSV, YUOV and GIV as analysed using the Kyte and Doolittle algorithm [22] are somewhat variable, overall they show broadly similar patterns of conserved domains, indicating that the NS4 proteins are generally hydrophilic ( figure 24 ).