Oropouche Virus: An Emerging Orthobunyavirus

Abstract

On 2 February 2024, the Pan American Health Organization/World Health Organization issued an epidemiological alert on rising Oropouche virus (OROV) infections in South America. By 3 August 2024, this alert level had escalated from medium to high. OROV has been a public health concern in Central and South America since its emergence in Brazil in the 1960s. However, the 2024 outbreak marks a turning point, with the sustained transmission in non-endemic regions of Brazil, local transmission in Cuba, two fatalities and several cases of vertical transmission. As of the end of August 2024, 9852 OROV cases have been confirmed. The 2024 OROV outbreak underscores critical gaps in our understanding of OROV pathogenesis and highlights the urgent need for antivirals and vaccines. This review aims to provide a concise overview of OROV, a neglected orthobunyavirus.

Keywords: Oropouche virus; arbovirus; emerging virus; orthobunyavirus; reassortment.

Fig. 1.. OROV emergence and transmission cycle. (a) Representation of the approximate geographic location of OROV emergence in Trinidad and Brazil. The map was generated using QGIS 3.38 [97]. (b) OROV transmission cycles. The sylvatic cycle involves various susceptible mammals and arthropods, and the urban cycle involves humans and primarily the biting midge Culicoides parenesis. The solid lines represent the independent sylvatic and urban cycles, while the dotted lines show their connection. OROV can ‘spill over’ into humans to initiate the urban cycle and ‘spill back’ into mammals and their vectors, thus maintaining OROV’s transmission cycle. The figure was created with Biorender.com (c) Images of potential OROV reservoirs, a marmoset and a sloth. Personal images taken in Brazil, 2013.

Fig. 2.. The 2024 OROV outbreak in Brazil. (a) Map of Brazil showing the cumulative cases by state from January 2024 to July 2024. AC, Acre; AP, Amapá; AL, Alagoas; AM, Amazonas; BA, Bahia; CE, Ceará; ES, Espírito Santo; PA, Pará; PB, Paraiba; PE, Pernambuco; PI, Piauí; PR, Pará; PR, Parana; MA, Maranhão; MG, Minas Gerais; MT, Mato Grosso; RO, Rondonia; RJ, Rio de Janeiro; SC, Santa Catarina; TO, Tocantins. (b) Number of confirmed OROV-positive cases by epidemiologic week covering January 2024 to July 2024. Data for the map and graph were collected from the Pan American Health Organization (PAHO)/WHO epidemiological alerts and updates [2,3, 19, 3943, 58]. The map was generated using QGIS 3.38 [97], and the graph was plotted in GraphPad Prism 10.

Fig. 3.. The 2024 OROV outbreak. (a) Cumulative OROV cases in Brazil, Bolivia, Columbia, Cuba, Dominican Republic and Peru. (b) OROV-affected areas highlighted: Brazil (pink), Peru (cyan), Bolivia (blue) and Columbia (sandy gold). Cuba is highlighted in green, while the Dominican Republic (DR) is left uncolored. Data for the graphs and map were sourced from PAHO/WHO epidemiological alerts and updates (last update 6 September 2024). The data may differ from actual numbers due to limitations in the available information [2,3, 19, 3943, 58]. The map was generated using QGIS 3.38 [97], and the graphs were plotted in GraphPad Prism 10.

Fig. 4.. Timeline of the 2024 OROV outbreak. Months of notable occurrences are shown. Circles in red highlight the months in which mortalities were reported. Data were collected from the PAHO/WHO and the European Centre for Disease Prevention and Control’s epidemiological updates [2,3, 19, 26, 3945, 58]. The figure was created with Biorender.com.

Fig. 5.. OROV symptoms. (a) Typical OROV symptoms. Signs and Symptoms recorded from patients in Amazonas in 2024. (b) Number of OROV cases classified by age and gender. Data for graphs was collected from [2,3, 19, 3943, 58, 110] and plotted in GraphPad Prism 10.

Fig. 6.. OROV biology. (a) Taxonomical classification of OROV. (b) OROV virion. The genome consists of S, small; M, medium and L, large segments. (c) Schematic of OROV genome. S encodes the nucleoprotein (n) and a non-structural (NSs) protein in overlapping reading frames. M encodes Gn, a non-structural protein (NSm), and Gc as a polyprotein, and L encodes the RNA-dependent RNA polymerase (RdRp, L protein). Untranslated regions (white boxes) flank the coding sequences. (d) Recombinant reporter OROV. Images collected from fluorescent reporter OROV-infected Vero-E6 cells 24 h post-infection [78]. Magnification 63X. (a–c) Created with Biorender.com.

Fig. 7.. OROV reassortants. (a) Schematic representation of orthobunyavirus reassortment. (b) Schematic representation of OROV reassortants. OROV, Oropouche virus (pink); MDDV, Madre de Dios virus (purple); IQTV, Iquitos (yellow); PDEV, Perdões virus (green) and JATV, Jatobal virus (blue). (a) and (b) were created with Biorender.com. (c) Phylogeny depicting the evolutionary relationship of OROV, MDDV, IQTV, PDEV and JATV based on the S, M and L coding sequences (CDS). Trees were created using a maximum-likelihood method based on the general time reversible model in Geneious. Accession numbers: Iquitos, S: KF697144, M: KF697143, L: KF697142; Perdões, S: KP691626, M: KP691625, L: KP691627; Oropouche, S: KP026181, M: KP026180, L: KP026179; Madre de Dios, S: KF697146, M: KF697145, L: KJ866391; Jatobal, S: JQ675601, M: JQ675602, L: JQ675603; Cat Que, S: OP129710, M: OP129711, L: OP129710; Schmallenberg, S: NC_043582, M: NC_043584, L: NC_043583; Shamonda, S: LC741389, M: LC741388, L: LC741387; Sathuperi, S: LC741386, M: LC741385, L: LC741384; Akabane, S: KY385908, M: KY381277, L: KY381282; Simbu, S: AF362397, M: NC_018478, L: NC_018476; Bunyamwera, S: NC_001927, M: NC_001926, L: NC_001925.