Mapping the evolutionary trajectories of morbilliviruses: what, where and whither

Abstract

Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators.

Figure 1

Schematic representation of the genomic organization of known and proposed morbilliviruses. MV = measles virus (blue), CDV = canine distemper virus (red), RPV = rinderpest virus (green), PPRV = peste des petits ruminants virus (light orange), PDV = phocine distemper (dark orange), CeMV = cetacean morbilliviruses (yellow), FeMV = feline morbillivirus (purple) and DrMV = vampire bat morbillivirus (light blue). Genomes are drawn to relative scale for comparison of the 3′ and 5′ termini, open reading frames and intergenic sequence length. Open reading frames represent the nucleocapsid (N), phospho- (P), matrix (M), fusion (F), hemagglutinin (H) and large (L) proteins which are present in the virions. The P/V/C gene encodes the non-structural V and C proteins. Four conserved hexamers in the 107 nucleotide (nt) 3′ leader sequence of MV are indicated (vertical red lines). The table lists known (gray) and proposed (white) morbilliviruses. Standard genome lengths, representative strains, proven CD150 and PVRL4 receptor use, 3′ M gene untranslated region (UTR) lengths, the sequence of the non-transcribed intergenic (Ig) trinucleotide spacer between the M and F genes, the length of the 5′ UTR of the F gene and available accession numbers on which the schematic diagrams, genome lengths etc. are based. Colors from this plate are used equivalently in figure 2 for clarity and comparability. * DrMV has not been isolated as a replicating virus.

Figure 2

Representation of the approximate global distribution of morbilliviruses throughout history. (a) MV (blue) and RPV (green) are the oldest morbilliviruses which were spread along ancient trade routes (red arrows). (b) Importation of MV to the New World and CDV (red) to the Old World during the Age of Exploration. (c) Spread of RPV to Africa and Asia due to the trans-border movement of cattle and establishment of MV as the first globally distributed morbillivirus (MV and CDV are not indicated for the purposes of clarity). Discovery of PPRV (light orange), PDV (dark orange) and CeMVs (yellow) in small ruminants, seals and cetaceans respectively. Development of MV, RPV, CDV and PPRV live attenuated vaccines (v). (d) Discovery FeMV (purple) a proposed novel member of the genus in Asia and the United States. Determination of the sequence of DrMV (light blue with dashed line) from clinical material obtained in Brazil. PPRV expands geographical range in Asia and Africa and is commonly isolated in Turkey and China. Resurgence of MV (blue with red line) in regions of the world where endemic transmission had ceased via air travel, areas where MV is endemic are omitted for clarity. Detection of CeMV (yellow) in a broader range of more widely distributed marine mammals. Eradication of RPV and discontinuation of vaccine use in cattle. CDV remains globally distributed and is not indicated for the purposes of clarity.

Figure 3

Phylogenetic relationships of morbilliviruses and related small mammal viruses. Bayesian phylogenetic reconstruction done using MrBayes V3.1 with 2 000 000 tree iterations sampled every 100 steps, corresponding to 20 000 trees of which 25% were discarded as burn-in. The final tree was annotated using TreeAnnotator and visualized using FigTree from the BEAST package. Hendra virus was used as an outgroup. Host orders are indicated by color and pictograms to the right. Prototype morbilliviruses and related viruses are indicated next to branches (JPV, J virus; BeiPV, Beilong virus; TuPV, Tupaia paramyxovirus; see text for other abbreviations). All available unclassified morbilli-related viruses (UMRV) that differed by more than 5% in their partial L gene sequences from any other virus, were from different hosts or different sampling countries were included into the analysis. The final dataset comprised 205 partial L gene sequences of 438 nucleotides generated by the RT-PCR assay described by [93] commonly used in paramyxovirus field studies.