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Akabane virus (AKAV), Aino virus, Peaton virus, Sathuperi virus, and Shamonda virus are arthropod-borne viruses belonging to the order Elliovirales, family Peribunyaviridae, genus Orthobunyavirus. These viruses cause or may cause congenital malformations in ruminants, including hydranencephaly, poliomyelitis, and arthrogryposis, although their pathogenicity may vary among field cases. AKAV may cause relatively severe congenital lesions such as hydranencephaly in calves. Furthermore, strains of AKAV genogroups I and II exhibit different disease courses. Genogroup I strains predominantly cause postnatal viral encephalomyelitis, while genogroup II strains are primarily detected in cases of congenital malformation. However, the biological properties of AKAV and other orthobunyaviruses are insufficiently investigated in hosts in the field and in vitro. Here, we used an immortalized bovine brain cell line (FBBC-1) to investigate viral replication efficiency, cytopathogenicity, and host innate immune responses. AKAV genogroup II and Shamonda virus replicated to higher titers in FBBC-1 cells compared with the other viruses, and only AKAV caused cytopathic effects. These results may be associated with the severe congenital lesions in the brain caused by AKAV genogroup II. AKAV genogroup II strains replicated to higher titers in FBBC-1 cells than AKAV genogroup I strains, suggesting that genogroup II strains replicated more efficiently in fetal brain cells, accounting for the detection of the latter strains mainly in fetal infection cases. Therefore, FBBC-1 cells may serve as a valuable tool for investigating the virulence and tropism of the orthobunyaviruses for bovine neonatal brain tissues in vitro.

In 2009, a mysterious illness associated with fever, thrombocytopenia, gastrointestinal symptoms, and leucopenia was seen in rural areas in central China, with an initial case fatality rate of 30%. After extensive investigation, a novel bunyavirus was identified. Between late March and mid-July 2009, an emerging infectious disease, which was identified as the severe fever with thrombocytopenia syndrome (SFTS), was reported in rural areas of Hubei and Henan provinces in Central China. The cause of the illness was unknown. The major clinical symptoms included fever, thrombocytopenia, gastrointestinal symptoms, and leukocytopenia, and there was an unusually high initial case fatality rate of 30%. In June 2009, an investigation was performed to identify whether the disease was caused by Anaplasma phagocytophilum or other pathogens. Although the clinical symptoms were considered to resemble those of human anaplasmosis, 1 neither bacterial DNA nor . . .

Background Mosquitoes in nature may acquire multiple bloodmeals (BMs) over the course of their lifetime; however, incorporation of frequent feeding behavior in laboratory vector competence studies is rarely done. We have previously shown that acquisition of a second non-infectious BM can enhance early dissemination of Zika virus (ZIKV), dengue virus, and chikungunya virus in Aedes aegypti and ZIKV in Aedes albopictus mosquitoes, yet it is unknown if other taxonomically-diverse virus-vector pairings show a similar trend under a sequential feeding regimen. Methods To test this, we evaluated the impact of a second noninfectious BM on the vector competence of Aedes aegypti and Anopheles quadrimaculatus for Mayaro virus, Culex quinquefasciatus for West Nile virus, Aedes triseriatus for La Crosse virus, and Aedes aegypti for Oropouche virus (OROV). Female mosquitoes were fed BMs containing these viruses and half of them were given a second noninfectious BM at 3 or 4-days post infection. Mosquitoes were harvested at various time points and assayed for virus infection in bodies and disseminated infection in legs by performing reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays. Results We found that a second noninfectious BM had no impact on midgut infection rates but increased virus dissemination for all but one of the virus-vector pairings- Ae . aegypti and OROV. Unlike the other arboviruses under consideration, which are strictly mosquito-borne, biting midges ( Culicoides spp.) serve as the main vector of OROV and this virus rarely disseminated to the mosquito leg tissue in our study. Conclusions Taken together, our findings show that sequential blood feeding enhances virus dissemination across diverse arbovirus-vector pairings, representing three mosquito genera and virus families, but a second BM was insufficient to overcome a strong midgut virus escape barrier in a nonnatural virus–vector pairing. Graphical Abstract

We detected Shuni virus in horses and ovine fetuses and Shamonda virus in a caprine fetus in South Africa. We identified a Shuni/Shamonda virus reassortant in a horse and Shuni/Caimito, Shamonda/Caimito, and Shamonda/Sango virus reassortants in Culicoides midges. Continued genomic surveillance will be needed to detect orthobunyavirus infections in Africa.

Oropouche virus (OROV) is a vector-borne zoonotic virus that causes febrile illness in humans. Biting midges of the Culicoides genus are the primary vectors during human outbreaks. The 2022–2024 OROV outbreak has seen an increase in incidence, geographic expansion, and the emergence of previously undocumented symptoms. To better understand the basis of increased disease incidence, infection of the outbreak virus (OROV 240023 ) was compared to a historical virus strain (rOROV BeAn19991 ) in Culicoides sonorensis , a midge species that has demonstrated historical competence. Higher levels of infection, dissemination, and transmission potential were observed in C. sonorensis infected with the outbreak strain compared to the historical strain, although infectious titers did not differ between the two viruses. OROV 240023 was also detected in saliva at earlier time points than rOROV BeAn19991 , indicating a shorter extrinsic incubation period of < 5 days compared to 7–14 days for rOROV BeAn19991 . Taken together, our results demonstrate increased transmission potential of the outbreak strain in C. sonorensis midges, raising concern about the risk of spread within the United States following potential introduction. However, further studies are needed to evaluate the current strain in Culicoides species occurring within its outbreak range, including Culicoides paraensis , the confirmed South American vector of OROV.

The whole-genome sequences of orthobunyaviruses isolated from cattle reared on Yonaguni Island (the western-most point of Japan's territory) were determined. The sequences of their S and L RNA segments were observed to be almost identical to those of Shamonda virus (SHAV) isolates identified in Japan, whereas the sequences of their M RNA segments were very similar to those of Japanese isolates of Sathuperi virus (SATV). Our findings indicate that the two novel isolates are natural reassortants between SHAV and SATV, which share a genome segment organization similar to that of Schmallenberg virus. The nucleotide sequence of the 5' non-coding region of the novel isolates differs from those of previously sequenced SATV isolates, suggesting that the M RNA segments of the reassortants were not derived from SATV strains that were detected recently in Japan.

Since its discovery in 1955, the incidence and geographical spread of reported Oropouche virus (OROV) infections have increased. Oropouche fever has been suggested to be one of the most important vector-borne diseases in Latin America. However, both literature on OROV and genomic sequence availability are scarce, with few contributing laboratories worldwide. Three reassortant OROV glycoprotein gene variants termed Iquitos, Madre de Dios, and Perdões virus have been described from humans and non-human primates. OROV predominantly causes acute febrile illness, but severe neurological disease such as meningoencephalitis can occur. Due to unspecific symptoms, laboratory diagnostics are crucial. Several laboratory tests have been developed but robust commercial tests are hardly available. Although OROV is mainly transmitted by biting midges, it has also been detected in several mosquito species and a wide range of vertebrate hosts, which likely facilitates its widespread emergence. However, potential non-human vertebrate reservoirs have not been systematically studied. Robust animal models to investigate pathogenesis and immune responses are not available. Epidemiology, pathogenesis, transmission cycle, cross-protection from infections with OROV reassortants, and the natural history of infection remain unclear. This Review identifies Oropouche fever as a neglected disease and offers recommendations to address existing knowledge gaps, enable risk assessments, and ensure effective public health responses.

Key Points Orthobunyaviruses are arthropod-transmitted viruses that are characterized by a tripartite, negative-sense RNA genome. Some viruses in this family are associated with diseases in humans (such as fever and encephalitis) and domesticated animals (including abortion and teratogenic effects in offspring). Schmallenberg virus, which is a recently emerged member of the family, caused a disease outbreak in domesticated animals in Europe in 2012–2013. Viral replication occurs in the cytoplasm of infected cells and viruses mature by budding in the Golgi complex. Although infection of mammalian cells usually results in cell death, replication in arthropod vector cells is not cytopathic and these cells become persistently infected. Viral mRNA synthesis is primed by capped oligonucleotides that are derived from host cell mRNAs in a process that is known as cap snatching. The endonuclease activity that is responsible for generating the primers is contained in the amino-terminal domain of the viral RNA-dependent RNA polymerase protein. The three-dimensional structure of the viral N (nucleocapsid) protein shows that it forms a tetramer that contains a novel fold with a central, positively charged groove that binds to the viral RNA. The viral non-structural protein NSs is the major virulence factor and antagonizes the host innate immune response by causing global inhibition of RNA polymerase II-mediated transcription. Possession of a segmented genome enables orthobunyaviruses to evolve rapidly by segment reassortment during mixed infections. Reassortment occurs widely in nature and reassortant viruses can have dramatically altered properties, such as increased virulence. Little is known about the burden of orthobunyavirus disease and there is a need for improved global surveillance to monitor orthobunyavirus activity. Orthobunyaviruses are transmitted by arthropod vectors and can infect humans, animals and crops. In this Review, Elliott describes recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication, and viral interactions with the host innate immune response. Orthobunyaviruses, which have small, tripartite, negative-sense RNA genomes and structurally simple virions composed of just four proteins, can have devastating effects on human health and well-being, either by causing disease in humans or by causing disease in livestock and crops. In this Review, I describe the recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication and viral interactions with the host innate immune response. Lastly, I highlight outstanding questions and areas of future research.

Oropouche virus is an arthropod-borne virus that has caused outbreaks of Oropouche fever in central and South America since the 1950s. This study investigates virological factors contributing to the re-emergence of Oropouche fever in Brazil between 2023 and 2024. In this observational epidemiological study, we combined multiple data sources for Oropouche virus infections in Brazil and conducted in-vitro and in-vivo characterisation. We collected serum samples obtained in Manaus City, Amazonas state, Brazil, from patients with acute febrile illnesses aged 18 years or older who tested negative for malaria and samples from people with previous Oropouche virus infection from Coari municipality, Amazonas state, Brazil. Basic clinical and demographic data were collected from the Brazilian Laboratory Environment Management System. We calculated the incidence of Oropouche fever cases with data from the Brazilian Ministry of Health and the 2022 Brazilian population census and conducted age–sex analyses. We used reverse transcription quantitative PCR to test for Oropouche virus RNA in samples and subsequently performed sequencing and phylogenetic analysis of viral isolates. We compared the phenotype of the 2023–24 epidemic isolate (AM0088) with the historical prototype strain BeAn19991 through assessment of titre, plaque number, and plaque size. We used a plaque reduction neutralisation test (PRNT50) to assess the susceptibility of the novel isolate and BeAn19991 isolate to antibody neutralisation, both in serum samples from people previously infected with Oropouche virus and in blood collected from mice that were inoculated with either of the strains. 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73–325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10 557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralising capacity (ie, median PRNT50 titre of 640 [IQR 320–640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype. These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to an improved understanding of the 2023–24 Oropouche virus re-emergence. Our exploratory in-vitro data suggest that the increased incidence might be related to a higher replication efficiency of a new Oropouche virus reassortant for which previous immunity shows lower neutralising capacity. São Paulo Research Foundation, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, and Brazilian National Council for Scientific and Technological Development. For the Portuguese translation of the abstract see Supplementary Materials section.

A febrile man in Italy who had traveled to Cuba in July 2024 was diagnosed with Oropouche fever. Reverse transcription PCR detected prolonged shedding of Oropouche virus RNA in whole blood, serum, urine, and semen. Sixteen days after symptom onset, replication-competent virus was detected in semen, suggesting risk for sexual transmission.