Comparative evolutionary analyses of peste des petits ruminants virus genetic lineages

Abstract

Peste des petits ruminants virus (PPRV) causes a highly infectious disease affecting mainly goats and sheep in large parts of Africa, Asia, and the Middle East and has an important impact on the global economy and food security. Full genome sequencing of PPRV strains has proved to be critical to increasing our understanding of PPR epidemiology and to inform the ongoing global efforts for its eradication. However, the number of full PPRV genomes published is still limited and with a heavy bias towards recent samples and genetic Lineage IV (LIV), which is only one of the four existing PPRV lineages. Here, we generated genome sequences for twenty-five recent (2010-6) and seven historical (1972-99) PPRV samples, focusing mainly on Lineage II (LII) in West Africa. This provided the first opportunity to compare the evolutionary pressures and history between the globally dominant PPRV genetic LIV and LII, which is endemic in West Africa. Phylogenomic analysis showed that the relationship between PPRV LII strains was complex and supported the extensive transboundary circulation of the virus within West Africa. In contrast, LIV sequences were clearly separated per region, with strains from West and Central Africa branched as a sister clade to all other LIV sequences, suggesting that this lineage also has an African origin. Estimates of the time to the most recent common ancestor place the divergence of modern LII and LIV strains in the 1960s-80s, suggesting that this period was particularly important for the diversification and spread of PPRV globally. Phylogenetic relationships among historical samples from LI, LII, and LIII and with more recent samples point towards a high genetic diversity for all these lineages in Africa until the 1970s-80s and possible bottleneck events shaping PPRV's evolution during this period. Molecular evolution analyses show that strains belonging to LII and LIV have evolved under different selection pressures. Differences in codon usage and adaptative selection pressures were observed in all viral genes between the two lineages. Our results confirm that comparative genomic analyses can provide new insights into PPRV's evolutionary history and molecular epidemiology. However, PPRV genome sequencing efforts must be ramped up to increase the resolution of such studies for their use in the development of efficient PPR control and surveillance strategies.

Keywords: endemic; epizootic; evolution; morbillivirus; phylogenetics; small ruminants.

Figure 1.

Map of the geographical location of PPRV samples sequenced in this study. The small map in the upper right corner indicates the countries sampled in Africa and the position of the sample collected in Sudan. The sample from India is not represented. Samples belonging to PPRV genetic LI are represented by a triangle, LII by a circle, and LIII by a diamond (in the small map). The symbols used differentiate historical samples (date <2000) from recent samples. Numbers within the symbols indicate the number of samples sequenced, if there is more than one per location.

Figure 2.

Time-dependent phylogenomic tree of PPRV. The four PPRV genetic lineages (LI, LII, LII, LIV) are represented by coloured backgrounds. Nodes of the tree with estimated TMRCA are indicated with a coloured circle for nodes joining PPRV sequences and by letters for deeper nodes in the tree, as indicated in the text and Table 2. Names of nodes of specific interest follow Table 2: LII recent (LIIr), LIV Asia (LIVa), LIV North-East Africa (LIVne), and LIV Middle East (LIVme). Names of PPRV strains sequenced for this study are indicated in bold. Asterisks indicate the few nodes of the tree with poor posterior probability <0.9.

Figure 3.

Heatmap of RSCU showing codons used more (>1) or less (<1) than expected in PPRV genes in LII and LIV. Codons with RSCU which significantly differ between lineages (P < 0.05, after correction) are in darker shades of colour. Cases of codons used more than expected for one lineage but used less for another are framed.

Figure 4.

Kernel density estimates of codon usage for each PPRV gene using coding sequences belonging to PPRV LII and LIV, as calculated with the mean CAI (panel on the left), using the genome of O. aries as a reference, and with the ENC (panel on the right).

Figure 5.

Pearson’s r correlation between CAI and ENC for Genes M, H, and L of PPRV strains belonging to LII (left column) and LIV (right column). All correlation results are detailed in Table 4.