Molecular epidemiology of Oropouche virus, Brazil

Abstract

Oropouche virus (OROV) is the causative agent of Oropouche fever, an urban febrile arboviral disease widespread in South America, with >30 epidemics reported in Brazil and other Latin American countries during 1960-2009. To describe the molecular epidemiology of OROV, we analyzed the entire N gene sequences (small RNA) of 66 strains and 35 partial Gn (medium RNA) and large RNA gene sequences. Distinct patterns of OROV strain clustered according to N, Gn, and large gene sequences, which suggests that each RNA segment had a different evolutionary history and that the classification in genotypes must consider the genetic information for all genetic segments. Finally, time-scale analysis based on the N gene showed that OROV emerged in Brazil ≈223 years ago and that genotype I (based on N gene data) was responsible for the emergence of all other genotypes and for virus dispersal.

Figure 1

Phylogenetic analysis between Oropouche virus (OROV) (N gene: 693 nt) and homologue sequences of different viruses that belong to the Simbu group. AINOV, Aino virus; AKAV, Akabane virus; TINV, Tinaroo virus; BUTV, Buttonwillow virus; FPV, Facey’s Paddock virus; MERV, Mermet virus; INGV, Ingwavuma virus. The numbers above each main node correspond to bootstrap values for phylogenetic groups. Scale bar indicates 10% genetic divergence.

Figure 2

Phylogenetic tree based on the complete nucleotide (nt) sequence of the N gene (693 nt) of 96 Oropouche virus (OROV) strains isolated from different hosts, locations, and periods. The main phylogenetic groups are represented by genotypes I (red), II (dark blue), III (green), and IV (light blue). The values above the main nodes represent the dates of emergence of common ancestors, expressed in years before 2009. The arrows indicate the probable date of emergence of genotypes I, II, III, and IV. Numbers in parentheses are value for 95% highest probability density. Scale bar indicates time scale of molecular dating. MRCA, most recent common ancestor.

Figure 3

Phylogenetic analysis of 36 Oropouche virus strains: A) N gene (693 nt), B) Gn gene (644 nt), and C) large (L) gene (634 nt), showing different topologies. Bootstrap values obtained by using maximum parsimony and neighbor-joining methods are placed over each main node of the tree corresponding to the phylogenetic groupings. The arrow indicates the exact position of the bootstrap value in the tree. Scale bars indicate 10% nt divergence.

Figure 4

Geographic dispersion of Oropouche virus (OROV) genotypes in South America during 1955–2009 based on data from the N gene. Yellow shading, coverage area of OROV in Brazil; red line, dispersion route for genotype I; blue line, dispersion route for genotype II; green line, dispersion route for genotype III; black dot, genotype IV. AC, Acre; AP, Amapá; AM, Amazonas; MA, Maranhão; MG, Minas Gerais; PA, Pará; RO, Rondônia, TO, Tocantins.