Fig 4. Phylogenetic trees depicting the genetic relationships between the nucleotide sequences derived from sub-genomic regions of species C enteroviruses.

Maximum likelihood trees were inferred from specific alignments of partial nucleotide sequences of the VP1, 2C^ATPase and 3D^pol coding genes [nucleotide positions 2482 to 2953 for VP1 (A); 4123 to 4922 for 2C^ATPase (B); 6166 to 6837 for 3D^pol (C) according to the complete genome sequence of Sabin 2]. Branch lengths were calculated using the best-fit model of nucleotide substitution estimated with Smart Model Selection based on the Bayesian Information Criterion: GTR+G for the VP1 (A), and 3D^pol (C) regions and GTR+G+I for the 2C^ATPase (B) region. Phylogenetic lineages of CV-A13 are indicated on the VP1 (A) and 2C^ATPase (B) derived trees using letters A to F. The genetic distance is indicated with a scale bar at the bottom. Numbers at nodes correspond to the percentage of 1,000 bootstrap replicates supporting the distal cluster. Since databases available sequences of wild polioviruses as well as most non-polio enteroviruses species C originating from other epidemiologic context featured no peculiar relationships with the studied isolates, most of them were omitted from the final datasets. However, selected poliovirus strains isolated during type 1, 2 and 3 cVDPV-associated outbreaks in Egypt (Sab2.Egy88, Sab2.Egy93), Madagascar (MAD04 and MAD29), Haiti (Sab1.HAI03, Sab1.HAI07), Dominican Republic (Sab1.Dor13), Philippines (Sab1.Phi01) and Cambodia in 2002 (Sab3.Cam02) were included. Trees were oriented using the nucleotide sequences of Enterovirus D70 (EV-D70) as outgroup. cVDPV isolates obtained from paralyzed patients from 2008 to 2012 and Coxsackievirus A viruses isolated from healthy children in 2013 in the Maniema (MAN) and Kasai Oriental (KOR) provinces of DR Congo are highlighted with circles color-coded according virus types: red for cVDPV, blue for CV-A13, green for the unique CV-A17 and purple for CV-A20 isolates. cVDPV identifiers include: “R” standing for DR Congo; “two digit code” indicating the year of isolation (08, 2008; 09, 2009; 10, 2010; 11, 2011 and 12, 2012) and “four digit code” representing the serial number. For clarity, some clusters defined by homotypic virus isolates were collapsed: Phi., Philippines; Dom. Rep., Domican Republic; Eq. and ka., Equateur and Katanga provinces of DR Congo. EV-C types and/or cVDPV sequences featuring peculiar relationships discussed in the text are gathered in grey-shaded boxes.