Therefore, Cisplatin research buy these residues could be of antigenic significance in serotype A viruses which requires further investigation. Phylogenetically, the viruses were grouped into two topotypes (African and Asian) within serotype A FMDV. In East Africa, only four genotypes (I, II, IV, and VII; Fig. 2) of African topotype viruses were found to be circulating, along with four viruses from Egypt and five viruses

from COD. Interestingly, all the viruses isolated from COD belong to genotype I (Fig. 2), similar to isolates from neighbouring countries such as Tanzania and Kenya, suggesting cross-border livestock movement and/or trade between these countries as observed in Uganda [40], Libya and Egypt [37]. A-EA-1981 virus was assigned to genotype II, however no further viruses of this genotype have been detected in the region since. The Asian topotype viruses (A-IRAN-2005 like viruses) were detected only in Egypt and Libya. These viruses were also detected in 2013 in Egypt and may still be circulating in the region. The scenario in Egypt is further complicated by circulation of two African Cyclopamine chemical structure genotypes (G IV and VII; Fig. 2) thereby making FMD control

very difficult. The introduction of A-IRAN-2005 like viruses to Africa could be the result of trade between the Middle East and African countries [37]. BEAST analysis using selected models revealed that the mean rate of nucleotide substitution in the capsid coding region of the viruses (year of isolation 1964 to 2012) was estimated to be 3.09 × 10−3 substitution/site/year (95% HPD 2.02 × 10−3 to 4.16 × 10−3). This is lower than the rate

reported for VP1 sequences of serotype A viruses [41] and that for P1 sequences of A-Iran-05 like viruses from the middle-East [26]. The mean estimate of the time of emergence for the most recent common ancestor was found to be about 128 years before the present (ybp) [95% highest posterior density (HPD): ADAMTS5 69 to 212]. This compares to a previous estimate of about 178 ybp (in 1823) for the emergence of serotype A viruses [41]. According to our estimation, the common ancestor of East Africa serotype A viruses existed around 1926 (Fig. 2). Analysis of the variability of the capsid amino acids of the type A viruses from East-Africa revealed VP4 to be highly conserved and VP1 to be highly variable (Table 2a and Fig. 3a); similar to earlier reports on type A viruses from the Middle East [26]. The residues with a score greater than 1.0 (16 in VP1, 10 in VP2 and 3 in VP3) are shown in Fig. 3a indicating that more than 50% of the residues with a high variability score are present in VP1. All but two (VP1-33 and VP2-207) of these residues were found to be surface exposed (Fig. 3b–d). The association between the numbers of aa changes and the serological reactivity (expressed as probability of protection; r1-value ≥0.3) between vaccine and virus strain pairs was assessed using a GLM model.