Full Genome Characterization of the First Oropouche Virus Isolate Imported in Europe from Cuba

Abstract

On 27 May 2024, the Cuban Ministry of Health reported the first outbreak of Oropouche fever on the island. The etiologic agent, Oropouche virus (OROV), is a poorly understood arbovirus that has been known since the 1960s and represents a public health burden in Latin America. We report the whole-genome characterization of the first European OROV isolate from a returning traveler from Cuba with Oropouche fever-like symptoms. The isolate was obtained from the patient's serum; whole-genome sequencing was performed by next-generation sequencing, followed by phylogenetic analysis and genetic variability studies. The analysis showed that the most closely related sequence was from the French Guiana 2020 outbreak. Interestingly, our isolate is a reassortant virus, included in a highly supported monophyletic clade containing recent OROV cases (Brazil 2015-Colombia 2021), separated from the other four previously known genotypes. More deeply, it was found to be included in a distinct branch containing the sequences of the Brazil 2022-2024 outbreak. The reassortment event involved the S and L segments, which have high similarity with sequences belonging to a new cluster (here defined as OROV_SCDC_2024), while the M segment shows high similarity with older sequences. These results likely describe the viral strain responsible for the current outbreak in Cuba, which may also reflect the ongoing outbreak in Latin America. Further studies are needed to understand how OROV evolves towards traits that facilitate its spread and adaptation outside its original basin, and to track its spread and evolution in the European continent.

Keywords: Oropouche fever; Oropouche virus; arbovirus; bunyavirus; emerging infectious diseases; phylogenetic analysis.

Figure 1

Phylogenetic analysis of OROV sequences of S (panel (A); n = 60), M (panel (B); n = 64) and L segment (panel (C); n = 64). ML tree based is rooted on the MDDV sequence used as outgroup. The scale bar represents the nucleotide distance, and the gray circles represents the bootstrap values (>85). The sequences already assigned to the 4 established genotypes according to the literature [13] are highlighted with different character colors. Sequences not yet included into a known genotype are in black characters. The sequence of the OROV_{IRCCS-SCDC_1/2024} here described for the first time (S segment ID: PP952117.2; M segment ID: PP952118.2; and L segment ID: PP952119.2) are highlighted with an orange dot. The distinct cluster OROV_SCDC_2024 is squared with an orange rectangle.

Figure 2

RDP output for OROV_{IRCCS-SCDC_1/2024}. The three segments’ collated sequences (S + M + L) were imputed in the RDP tool for the reassortment analysis. Interface between segments S and M (panel (A)) and interface between segment M and L (panel (B)) are reported. The sequences resulting with the highest pairwise identity with OROV_{IRCCS-SCDC_1/2024} for S, M and L regions are reported (green and purple lines). The reassortment is indicated by the presence of significative breakpoints detected in pairwise sequence alignment. Grey areas highlight the breakpoints of the collated sequences with their associated p values.