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Oropouche virus is the aetiological agent of Oropouche fever. At present, this is currently considered one of the most important vector-borne diseases in Latin America. On 27 May 2024, the Ministry of Public Health of Cuba reported the first ever outbreak of Oropouche fever. In this report, we describe three human cases of Oropouche virus infection with symptoms and signs of neurological disease and clinical diagnosis of Guillain-Barré Syndrome. This study offers insights regarding that Oropouche virus is a causal agent of neurological disorders and it could be involved in the etiology of the Guillain-Barré Syndrome. [ABSTRACT FROM AUTHOR]

The Oropouche virus (OROV) is emerging as a major public health threat worldwide, yet for the Americas, it raises complex challenges that intersect with other existing arboviral threats such as Zika (ZIKV), dengue (DENV) and Chikungunya (CHIKV) viruses. Originating from Trinidad and Tobago in 1955, it has spread across the Amazonian Basin and more recently into the Caribbean (Cuba and Haiti) and Europe, highlighting the importance of air travel in its dissemination. OROV and the less studied Melao virus (MELV), pose significant laboratory diagnostic challenges particularly in regions co-endemic with other arboviral diseases, such as dengue and Zika fever. The effects of climate change, particularly in the Caribbean, may exacerbate the transmission of these viruses by exposing human exposure risk to vectors. Public health systems in the Americas are under strain due to complex clinical management of these infections necessitating enhanced surveillance, clinical vigilance, diagnostics and vector control. Vulnerable populations, including pregnant women, elderly, and young children, are at a heightened risk, which raises concerns about the impact on medical tourism in the region. To mitigate the spread and impact of OROV and MELV, recommendations include increased clinical surveillance, improved laboratory diagnostics, public health communication, and strengthened vector controls. Robust research and capacity building (including training and education) efforts are essential to address knowledge gaps and effectively manage future OROV and MELV outbreaks in the Americas. [ABSTRACT FROM AUTHOR]

Oropouche Virus (OROV; genus of Orthobunyavirus) is the causal agent of Oropouche Fever (OF). Due to the lack of specific signs and symptoms and the limited availability of diagnostic tests, the actual epidemiology of OROV infections and OF has been extensively disputed. In this systematic review with meta-analysis, a literature search was carried out in PubMed, Scopus, EMBASE, and MedRxiv in order to retrieve relevant articles on the documented occurrence of OROV infections. Pooled detection rates were then calculated for anti-OROV antibodies and virus detection (i.e., viral RNA detected by viral cultures and/or real-time polymerase chain reaction [RT-qPCR]). Where available, detection rates for other arboviruses (i.e., Dengue [DENV], Chikungunya [CHKV], and Zika Virus [ZIKV]) were calculated and compared to those for OROV. A total of 47 studies from South America and the Caribbean were retrieved. In individuals affected by febrile illness during OROV outbreaks, a documented prevalence of 0.45% (95% confidence interval [95%CI] 0.16 to 1.12) for virus isolation, 12.21% (95%CI 4.96 to 27.09) for seroprevalence (including both IgM and IgG class antibodies), and 12.45% (95%CI 3.28 to 37.39) for the detection of OROV-targeting IgM class antibodies were eventually documented. In the general population, seroprevalence was estimated to be 24.45% (95%CI 7.83 to 55.21) for IgG class antibodies. The OROV detection rate from the cerebrospinal fluids of suspected cases of viral encephalitis was estimated to be 2.40% (95%CI 1.17 to 5.03). The occurrence of OROV infections was consistently lower than that of DENV, CHKV, and ZIKV during outbreaks (Risk Ratio [RR] 24.82, 95%CI 21.12 to 29.16; RR 2.207, 95%CI 1.427 to 3.412; and RR 7.900, 95%CI 5.386 to 11.578, respectively) and in the general population (RR 23.614, 95%CI 20.584 to 27.129; RR 3.103, 95%CI 2.056 to 4.685; and RR 49.500, 95%CI 12.256 to 199.921, respectively). In conclusion, our study stresses the possibly high underestimation of OROV prevalence in the general population of South America, the potential global threat represented by this arbovirus infection, and the potential preventive role of a comprehensive "One Health approach". [ABSTRACT FROM AUTHOR]

Fort Sherman virus (FSV) was isolated in Panama in 1985 from a US soldier. We report a case of human FSV infection in a febrile patient from northern coastal Peru in 2020. FSV infections spanning ≈35 years and a distance of 2,000 km warrant diagnostics, genomic surveillance, and investigation of transmission cycles.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

Bunyaviruses are enveloped negative or ambisense single-stranded RNA viruses with a genome divided into several segments. The canonical view depicts each viral particle packaging one copy of each genomic segment in one polarity named the viral strand. Several opposing observations revealed nonequal ratios of the segments, uneven number of segments per virion, and even packaging of viral complementary strands. Unfortunately, these observations result from studies often addressing other questions, on distinct viral species, and not using accurate quantitative methods. Hence, what RNA segments and strands are packaged as the genome of any bunyavirus remains largely ambiguous. We addressed this issue by first investigating the virion size distribution and RNA content in populations of the tomato spotted wilt virus (TSWV) using microscopy and tomography. These revealed heterogeneity in viral particle volume and amount of RNA content, with a surprising lack of correlation between the two. Then, the ratios of all genomic segments and strands were established using RNA sequencing and qRT-PCR. Within virions, both plus and minus strands (but no mRNA) are packaged for each of the three L, M, and S segments, in reproducible nonequimolar proportions determined by those in total cell extracts. These results show that virions differ in their genomic content but together build up a highly reproducible genetic composition of the viral population. This resembles the genome formula described for multipartite viruses, with which some species of the order Bunyavirales may share some aspects of the way of life, particularly emerging properties at a supravirion scale.

Whole-genome sequencing of a virus isolated from Culicoides biting midges in southern Japan in 2020 revealed that it is a strain of Balagodu virus (BLGV; genus Orthobunyavirus; family Peribunyaviridae; order Bunyavirales). A solitary instance of BLGV isolation occurred in India in 1963. All assembled segments comprise complete protein-coding sequences that are similar to those of other orthobunyaviruses. The consensus 3'- and 5'-terminal sequences of orthobunyaviruses' genomic RNAs are also conserved in the Japanese BLGV strain. Here, we update the geographic distribution of BLGV and provide its complete sequence, contributing to the clarification of orthobunyavirus phylogeny. [ABSTRACT FROM AUTHOR]

Abstract Background Mosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk. Methods To investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR. Results The results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%. Conclusions The findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus. Graphical Abstract

Oropouche Virus (OROV; genus of Orthobunyavirus) is the causal agent of Oropouche Fever (OF). Due to the lack of specific signs and symptoms and the limited availability of diagnostic tests, the actual epidemiology of OROV infections and OF has been extensively disputed. In this systematic review with meta-analysis, a literature search was carried out in PubMed, Scopus, EMBASE, and MedRxiv in order to retrieve relevant articles on the documented occurrence of OROV infections. Pooled detection rates were then calculated for anti-OROV antibodies and virus detection (i.e., viral RNA detected by viral cultures and/or real-time polymerase chain reaction [RT-qPCR]). Where available, detection rates for other arboviruses (i.e., Dengue [DENV], Chikungunya [CHKV], and Zika Virus [ZIKV]) were calculated and compared to those for OROV. A total of 47 studies from South America and the Caribbean were retrieved. In individuals affected by febrile illness during OROV outbreaks, a documented prevalence of 0.45% (95% confidence interval [95%CI] 0.16 to 1.12) for virus isolation, 12.21% (95%CI 4.96 to 27.09) for seroprevalence (including both IgM and IgG class antibodies), and 12.45% (95%CI 3.28 to 37.39) for the detection of OROV-targeting IgM class antibodies were eventually documented. In the general population, seroprevalence was estimated to be 24.45% (95%CI 7.83 to 55.21) for IgG class antibodies. The OROV detection rate from the cerebrospinal fluids of suspected cases of viral encephalitis was estimated to be 2.40% (95%CI 1.17 to 5.03). The occurrence of OROV infections was consistently lower than that of DENV, CHKV, and ZIKV during outbreaks (Risk Ratio [RR] 24.82, 95%CI 21.12 to 29.16; RR 2.207, 95%CI 1.427 to 3.412; and RR 7.900, 95%CI 5.386 to 11.578, respectively) and in the general population (RR 23.614, 95%CI 20.584 to 27.129; RR 3.103, 95%CI 2.056 to 4.685; and RR 49.500, 95%CI 12.256 to 199.921, respectively). In conclusion, our study stresses the possibly high underestimation of OROV prevalence in the general population of South America, the potential global threat represented by this arbovirus infection, and the potential preventive role of a comprehensive “One Health approach”.

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to (1) characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; (2) examine the diagnostic assays that have undergone development and validation for this group of viruses; and (3) describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence, and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Given significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities. [ABSTRACT FROM AUTHOR]

Bataï virus (BATV), belonging to the Orthobunyavirus genus, is an emerging mosquito-borne virus with documented cases in Asia, Europe, and Africa. It causes various symptoms in humans and ruminants. Another related virus is Ilesha virus (ILEV), which causes a range of diseases in humans and is mainly found in African countries. This study aimed to genetically identify and characterize a BATV strain previously misclassified as ILEV in Senegal. The strain was reactivated and subjected to whole genome sequencing using an Illumina-based approach. Genetic analyses and phylogeny were performed to assess the evolutionary relationships. Genomic analyses revealed a close similarity between the Senegal strain and the BATV strains UgMP-6830 from Uganda. The genetic distances indicated high homology. Phylogenetic analysis confirmed the Senegal strain's clustering with BATV. This study corrects the misclassification, confirming the presence of BATV in West Africa. This research represents the first evidence of BATV circulation in West Africa, underscoring the importance of genomic approaches in virus classification. Retrospective sequencing is crucial for reevaluating strains and identifying potential public health threats among neglected viruses. [ABSTRACT FROM AUTHOR]

In July 2018, a virus (JXLC1806-2) was isolated from Culicoides biting midges collected in Lichuan County, Jiangxi Province, China. The virus isolate showed significant cytopathic effects within 48 hours after inoculation with mammalian cells (BHK-21). JXLC1806-2 virus could form plaques in BHK-21 cells, and the virus titer was 1×105.6 pfu/mL. After inoculation with the virus, suckling mice developed disease and died. The nucleotide and amino sequence analysis showed that the JXLC1806-2 virus genome was composed of S, M and L segments. Phylogenetic analysis showed that the S, M and L genes of JXLC1806-2 virus belonged to the Tete serogroup, Orthobunyavirus, but formed an independent evolutionary branch from the other members of the Tete serogroup. The results showed that the JXLC1806-2 virus, which was named as Lichuan virus, is a new member of Tete serogroup, and this is the first time that a Tete serogroup virus has been isolated in China. [ABSTRACT FROM AUTHOR]

In Colombia, tropical febrile illnesses represent one of the most important causes of clinical attention. Febrile illnesses in the tropics are mainly zoonotic and have a broad etiology. The Colombian surveillance system monitors some notifiable diseases. However, several etiologies are not monitored by this system. In the present review, we describe eleven different etiologies of zoonotic tropical febrile illnesses that are not monitored by the Colombian surveillance system but have scientific, historical, and contemporary data that confirm or suggest their presence in different regions of the country: Anaplasma, Arenavirus, Bartonella, relapsing fever group Borrelia, Coxiella burnetii, Ehrlichia, Hantavirus, Mayaro virus, Orientia, Oropouche virus, and Rickettsia. These could generate a risk for the local population, travelers, and immigrants, due to which they should be included in the mandatory notification system, considering their importance for Colombian public health. [ABSTRACT FROM AUTHOR]

A 56-year-old man receiving rituximab who had months of neurologic symptoms was found to have Jamestown Canyon virus in cerebrospinal fluid by clinical metagenomic sequencing. The patient died, and postmortem examination revealed extensive neuropathologic abnormalities. Deep sequencing enabled detailed characterization of viral genomes from the cerebrospinal fluid, cerebellum, and cerebral cortex.

A 56-year-old man receiving rituximab who had months of neurologic symptoms was found to have Jamestown Canyon virus in cerebrospinal fluid by clinical metagenomic sequencing. The patient died, and postmortem examination revealed extensive neuropathologic abnormalities. Deep sequencing enabled detailed characterization of viral genomes from the cerebrospinal fluid, cerebellum, and cerebral cortex.

The Arctic is warming at four times the global rate, changing the diversity, activity and distribution of vectors and associated pathogens. While the Arctic is not often considered a hotbed of vector-borne diseases, Jamestown Canyon virus (JCV) and Snowshoe Hare virus (SSHV) are mosquito-borne zoonotic viruses of the California serogroup endemic to the Canadian North. The viruses are maintained by transovarial transmission in vectors and circulate among vertebrate hosts, both of which are not well characterized in Arctic regions. While most human infections are subclinical or mild, serious cases occur, and both JCV and SSHV have recently been identified as leading causes of arbovirus-associated neurological diseases in North America. Consequently, both viruses are currently recognised as neglected and emerging viruses of public health concern. This review aims to summarise previous findings in the region regarding the enzootic transmission cycle of both viruses. We identify key gaps and approaches needed to critically evaluate, detect, and model the effects of climate change on these uniquely northern viruses. Based on limited data, we predict that (1) these northern adapted viruses will increase their range northwards, but not lose range at their southern limits, (2) undergo more rapid amplification and amplified transmission in endemic regions for longer vector-biting seasons, (3) take advantage of northward shifts of hosts and vectors, and (4) increase bite rates following an increase in the availability of breeding sites, along with phenological synchrony between the reproduction cycle of theorized reservoirs (such as caribou calving) and mosquito emergence. [ABSTRACT FROM AUTHOR]

The genus Orthobunyavirus is a diverse group of viruses in the family Peribunyaviridae, recently classified into 20 serogroups, and 103 virus species. Although most viruses within these serogroups are phylogenetically distinct, the absence of complete genome sequences has left several viruses incompletely characterized. Here we report the complete genome sequences for 11 orthobunyaviruses isolated from Trinidad, French Guiana, Guatemala, and Panama that were serologically classified into six serogroups and 10 species. Phylogenetic analyses of these 11 newly derived sequences indicate that viruses belonging to the Patois, Capim, Guama, and Group C serocomplexes all have a close genetic origin. We show that three of the 11 orthobunyaviruses characterized (belonging to the Group C and Bunyamwera serogroups) have evidence of histories of natural reassortment through the M genome segment. Our data also suggests that two distinct lineages of Group C viruses concurrently circulate in Trinidad and are transmitted by the same mosquito vectors. This study also highlights the importance of complementing serological identification with nucleotide sequencing when characterizing orthobunyaviruses. [ABSTRACT FROM AUTHOR]

Schmallenberg virus (SBV) is an insect-transmitted orthobunyavirus that can cause abortions and congenital malformations in the offspring of ruminants. Even though the two viral surface glycoproteins Gn and Gc are involved in host cell entry, the specific cellular receptors of SBV are currently unknown. Using genome-wide CRISPR-Cas9 forward screening, we identified 3-phosphoadenosine 5-phosphosulfate (PAPS) transporter 1 (PAPST1) as an essential factor for SBV infection. PAPST1 is a sulfotransferase involved in heparan sulfate proteoglycan synthesis encoded by the solute carrier family 35 member B2 gene (SLC35B2). SBV cell surface attachment and entry were largely reduced upon the knockout of SLC35B2, whereas the reconstitution of SLC35B2 in these cells fully restored their susceptibility to SBV infection. Furthermore, treatment of cells with heparinase diminished infection with SBV, confirming that heparan sulfate plays an important role in cell attachment and entry, although to various degrees, heparan sulfate was also found to be important to initiate infection by two other bunyaviruses, La Crosse virus and Rift Valley fever virus. Thus, PAPST1-triggered synthesis of cell surface heparan sulfate is required for the efficient replication of SBV and other bunyaviruses.IMPORTANCE SBV is a newly emerging orthobunyavirus (family Peribunyaviridae) that has spread rapidly across Europe since 2011, resulting in substantial economic losses in livestock farming. In this study, we performed unbiased genome-wide CRISPR-Cas9 screening and identified PAPST1, a sulfotransferase encoded by SLC35B2, as a host entry factor for SBV. Consistent with its role in the synthesis of heparan sulfate, we show that this activity is required for efficient infection by SBV. A comparable dependency on heparan sulfate was also observed for La Crosse virus and Rift Valley fever virus, highlighting the importance of heparan sulfate for host cell infection by bunyaviruses. Thus, the present work provides crucial insights into virus-host interactions of important animal and human pathogens.

During April-June 2014 in a malaria-endemic rural community close to the city of Iquitos in Peru, we detected evidence of Guaroa virus (GROV) infection in 14 febrile persons, of whom 6 also had evidence of Plasmodium vivax malaria. Cases were discovered through a long-term febrile illness surveillance network at local participating health facilities. GROV cases were identified by using a combination of seroconversion and virus isolation, and malaria was diagnosed by thick smear and PCR. GROV mono-infections manifested as nonspecific febrile illness and were clinically indistinguishable from GROV and P. vivax co-infections. This cluster of cases highlights the potential for GROV transmission in the rural Peruvian Amazon, particularly in areas where malaria is endemic. Further study of similar areas of the Amazon may provide insights into the extent of GROV transmission in the Amazon basin.

Oropouche virus (OROV) is responsible for outbreaks of Oropouche fever in parts of South America. We recently identified and isolated OROV from a febrile Ecuadorian patient, however, a previously published qRT-PCR assay did not detect OROV in the patient sample. A primer mismatch to the Ecuadorian OROV lineage was identified from metagenomic sequencing data. We report the optimisation of an qRT-PCR assay for the Ecuadorian OROV lineage, which subsequently identified a further five cases in a cohort of 196 febrile patients. We isolated OROV via cell culture and developed an algorithmically-designed primer set for whole-genome amplification of the virus. Metagenomic sequencing of the patient samples provided OROV genome coverage ranging from 68-99%. The additional cases formed a single phylogenetic cluster together with the initial case. OROV should be considered as a differential diagnosis for Ecuadorian patients with febrile illness to avoid mis-diagnosis with other circulating pathogens.

Jamestown Canyon virus (JCV) is a mosquito-borne arbovirus that circulates in North America. We detected JCV in 4 pools of mosquitoes collected from midcoastal Maine, USA, during 2017–2019. Phylogenetic analysis of a JCV sequence obtained from Aedes cantator mosquitoes clustered within clade A, which also circulates in Connecticut, USA.

Abstract Background Akabane virus (AKAV) is a teratogenic and neuropathogenic arbovirus that infects livestock and wild animals. AKAVs are endemic arboviruses from dairy farms in Taiwan in 1989, and the first sequence was detected in cattle with nonsuppurative encephalitis in 1992. Objectives This study aims to understand the epidemiological relationships of the akabane viruses between Taiwan and nearby places. Methods In this study, 17 specimens were identified or isolated from vector insects, and ruminant fetuses collected from 1992 to 2015 were sequenced and analysed. Results Sequence analyses revealed all Taiwanese AKAVs belonged to genogroup Ia but diverged into two clusters in the phylogenetic trees, implying that at least two invasive events of AKAV may have occurred in Taiwan. Conclusions The two clusters of AKAVs could still be identified in Taiwan in 2015, and a reassortment event was observed, indicating that the two clusters of AKAVs are already endemic in Taiwan.

• A short fragment of the nucleoprotein of Schmallenberg virus has been identified as candidate subunit vaccine. • The candidate subunit vaccine reduces viraemia in infected mice. • The subunit vaccine shares high sequence homology with the nucleoproteins of the members of the Simbu serogroup. Schmallenberg Virus (SBV), an arbovirus from the Peribunyaviridae family and Orthobunyavirus genus, was discovered in late 2011 in Germany and has been circulating in Europe, Asia and Africa ever since. The virus causes a disease associated with ruminants that includes fever, fetal malformation, drop in milk production, diarrhoea and stillbirths, becoming a burden for small and large farms. Building on previous studies on SBV nucleoprotein (SBV-N) as a promising vaccine candidate, we have investigated the possible protein regions responsible for protection. Based on selective truncation of domains designed from the available crystal structure of the SBV-N, we identified both the N-terminal domain (N-term; Met1 – Thr133) and a smaller fragment within (C4; Met1 – Ala58) as vaccine prototypes. Two injections of the N-term and C4 polypeptides protected mice knockout for type I interferon (IFN) receptors (IFNAR-/-) challenged with virulent SBV, opposite to control groups that presented severe signs of morbidity and weight loss. Viremia analyses along with the presence of IFN-γ secreted from splenocytes re-stimulated with the N-terminal region of the protein corroborate that these two portions of SBV-N can be employed as subunit vaccines. Apart from both proteinaceous fragments being easily produced in bacterial cells, the C4 polypeptide shares a high sequence homology (∼87.1 %) with the corresponding region of nucleoproteins of several viruses of the Simbu serogroup, a group of Orthobunyaviruses that comprises SBV and veterinary pathogens like Akabane virus and human infecting viruses like Oropouche. Thus, we propose that this smaller fragment is better suited for vaccine nanoparticle formulation, and it paves the way to further research with other related Orthobunyaviruses. [ABSTRACT FROM AUTHOR]

Introduction: Tahyna virus (TAHV), an arbovirus of the genus Orthobunyavirus, is a cause of human diseases and less studied worldwide. In this study, a new strain of TAHV was isolated from Aedes sp. mosquitoes collected in Panjin city, Liaoning province. However, the competent vector of TAHV in China is still unknown. Methods: The genome of newly isolated TAHV was sequenced and phylogenetic analysis is performed. Aedes albopictus and Culex pipiens pallens were orally infected with artificial virus blood meals (1:1 of virus suspension and mouse blood), the virus was detected in the midgut, ovary, salivary gland and saliva of the mosquitoes. Then, the transmission and dissemination rates, vertical transmission and horizontal transmission of the virus by the mosquitoes were assessed. Methods: The genome of newly isolated TAHV was sequenced and phylogenetic analysis is performed. Aedes albopictus and Culex pipiens pallens were orally infected with artificial virus blood meals (1:1 of virus suspension and mouse blood), the virus was detected in the midgut, ovary, salivary gland and saliva of the mosquitoes. Then, the transmission and dissemination rates, vertical transmission and horizontal transmission of the virus by the mosquitoes were assessed. Methods: The genome of newly isolated TAHV was sequenced and phylogenetic analysis is performed. Aedes albopictus and Culex pipiens pallens were orally infected with artificial virus blood meals (1:1 of virus suspension and mouse blood), the virus was detected in the midgut, ovary, salivary gland and saliva of the mosquitoes. Then, the transmission and dissemination rates, vertical transmission and horizontal transmission of the virus by the mosquitoes were assessed. Results: Phylogenetic analysis revealed that the virus shared high similarity with TAHV and was named the TAHV PJ01 strain. After oral infection with virus blood meals, Ae. albopictus showed positive for the virus in all tested tissues with an extrinsic incubation period of 2 days and a fluctuating increasement of transmission and dissemination rates. Whereas no virus was detected in the saliva of Cx. pipiens pallens. Suckling mice bitten by infectious Ae. albopictus developed obvious neurological symptoms, including inactivity, hind-leg paralysis and difficulty turning over, when the virus titer reached 1.70×105 PFU/mL in the brain. Moreover, TAHV was detected in the eggs, larvae and adults of F1 offspring of Ae. albopictus. Discussion: Ae. albopictus is an efficient vector to transmit TAHV but Cx. pipiens pallens is not. Ae. albopictus is also a reservoir host that transmits the virus vertically, which further increases the risk of outbreaks. This study has important epidemiological implications for the surveillance of pathogenic viruses in China and guiding comprehensive vector control strategies to counteract potential outbreaks in future. [ABSTRACT FROM AUTHOR]

The first report about Ebinur Lake orthotobunyavirus (EBIV) detected in mosquito pools in the northern provinces of China was published in 2014. The south of the European part of the Russian Federation is a known area of some arboviral infection foci such as West Nile Fever due to favorable climatic and geographic conditions and being a part of the bird's migratory pathways. But very little is known about the spread of other bird-associated viruses. We describe here the first case of EBIV detection in the Volgograd region, Russia. The genomic RNA of EBIV was detected in bird brain tissues, mosquitoes (including overwintering ones) and ticks pools using metagenomic sequencing technique. Belonging of the detected RNA to EBIV (Orthobunyavirus, Peribunyaviridae) was confirmed by phylogenetic analysis. The simultaneous existence of EBIV and other arboviruses such as West Nile virus (WNV) and Sindbis virus (SINV) in environmental samples was revealed. The obtained results indicate the need for further studies of the EBIV circulation in the Volgograd region and possible epidemiological risks. [ABSTRACT FROM AUTHOR]

Bataï virus (BATV), belonging to the Orthobunyavirus genus, is an emerging mosquito-borne virus with documented cases in Asia, Europe, and Africa. It causes various symptoms in humans and ruminants. Another related virus is Ilesha virus (ILEV), which causes a range of diseases in humans and is mainly found in African countries. This study aimed to genetically identify and characterize a BATV strain previously misclassified as ILEV in Senegal. The strain was reactivated and subjected to whole genome sequencing using an Illumina-based approach. Genetic analyses and phylogeny were performed to assess the evolutionary relationships. Genomic analyses revealed a close similarity between the Senegal strain and the BATV strains UgMP-6830 from Uganda. The genetic distances indicated high homology. Phylogenetic analysis confirmed the Senegal strain’s clustering with BATV. This study corrects the misclassification, confirming the presence of BATV in West Africa. This research represents the first evidence of BATV circulation in West Africa, underscoring the importance of genomic approaches in virus classification. Retrospective sequencing is crucial for reevaluating strains and identifying potential public health threats among neglected viruses.

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to (1) characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; (2) examine the diagnostic assays that have undergone development and validation for this group of viruses; and (3) describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence, and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Given significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities.

Abstract Background Subsequent to its first detection in 2011, the insect-transmitted bunyavirus Schmallenberg virus (SBV; genus Orthobunyavirus) caused a large-scale epizootic of fetal malformation in the European ruminant population. By now, SBV established an enzootic status in Central Europe with regular wave-like re-emergence, which has prompted intensive research efforts in order to elucidate the pathogenesis and to develop countermeasures. Since different orthobunyaviruses share a very similar structural organization, SBV has become an important model virus to study orthobunyaviruses in general and for the development of vaccines. In this review article, we summarize which vaccine formulations have been tested to prevent SBV infections in livestock animals. Main In a first step, inactivated SBV candidate vaccines were developed, which efficiently protected against an experimental SBV infection. Due to the inability to differentiate infected from vaccinated animals (= DIVA capability), a series of further approaches ranging from modified live, live-vectored, subunit and DNA-mediated vaccine delivery to multimeric antigen-presentation on scaffold particles was developed and evaluated. In short, it was repeatedly demonstrated that the N-terminal half of the glycoprotein Gc, composed of the Gc head and the head-stalk, is highly immunogenic, with a superior immunogenicity of the complete head-stalk domain compared to the Gc head only. Furthermore, in all Gc protein-based vaccine candidates, immunized animals can be readily discriminated from animals infected with the field virus by the absence of antibodies against the viral N-protein. Conclusions Using SBV as a model virus, several vaccination-challenge studies in target species underscored the superior performance of antigenic domains compared to linear epitopes regarding their immunogenicity. In addition, it could be shown that holistic approaches combining immunization-challenge infection studies with structural analyses provide essential knowledge required for an improved vaccine design.

Culex spp. mosquitoes transmit several pathogens concerning public health, including West Nile virus and Saint Louis encephalitis virus. Understanding the antiviral immune system of Culex spp. mosquitoes is important for reducing the transmission of these viruses. Mosquitoes rely on RNA interference (RNAi) to control viral replication. While the siRNA pathway in mosquitoes is heavily studied, less is known about the piRNA pathway. The piRNA pathway in mosquitoes has recently been connected to mosquito antiviral immunity. In Aedes aegypti, Piwi4 has been implicated in antiviral responses. The antiviral role of the piRNA pathway in Culex spp. mosquitoes is understudied compared to Ae. aegypti. Here, we aimed to identify the role of PIWI genes and piRNAs in Culex quinquefasciatus and Culex tarsalis cells during virus infection. We examined the effect of PIWI gene silencing on virus replication of two arboviruses and three insect-specific viruses in Cx. quinquefasciatus derived cells (Hsu) and Cx. tarsalis derived (CT) cells. We show that Piwi4 is antiviral against the La Crosse orthobunyavirus (LACV) in Hsu and CT cells, and the insect-specific rhabdovirus Merida virus (MERDV) in Hsu cells. None of the silenced PIWI genes impacted replication of the two flaviviruses Usutu virus (USUV) and Calbertado virus, or the phasivirus Phasi-Charoen-like virus. We further used small RNA sequencing to determine that LACV-derived piRNAs, but not USUV-derived piRNAs were generated in Hsu cells and that PIWI gene silencing resulted in a small reduction in vpiRNAs. Finally, we determined that LACV-derived DNA was produced in Hsu cells during infection, but whether this viral DNA is required for vpiRNA production remains unclear. Overall, we expanded our knowledge on the piRNA pathway and how it relates to the antiviral response in Culex spp mosquitoes. [ABSTRACT FROM AUTHOR]

The Schmallenberg virus (SBV), an emerging Orthobunyavirus of mainly ruminant hosts, caused a substantial epidemic in European ruminant populations between 2011 and 2013. The pathogen is transmitted by arthropod vectors (Culicoides spp.) and can cause reproductive disorders and severe malformations of the offspring or stillbirth. The present study aimed to assess SBV seroprevalence among German sheep and goats a few years after the first virus detection in the country (November 2011). In addition, an extensive risk factor analysis including host-specific and husbandry-related factors was implemented. Seroprevalence was determined by examining serum samples from 2759 sheep and 446 goats out of a total of 70 flocks across five German federal states. The samples were withdrawn in the period between 2017 and 2018. Using a commercial competitive ELISA, antibodies against SBV were detected in all 70 investigated flocks. A percentage of 60.1 % (1657/2759) of the sheep and 40.4 % (180/446) of the goat sera contained SBV antibodies. Generalized linear mixed modeling revealed significant effects of host species (sheep > goats), age (old > young) and sex (female > male) on SBV seroprevalence. For both species, also the farming purpose, and for goats, ectoparasite treatment and the presence of cattle on the farm played a role in terms of risk for SBV exposure. The observations from this study still emphasize a wide distribution of the pathogen in Germany. Nevertheless, the observed seroprevalence might not be sufficient to achieve effective herd immunity. Pinpointing risk factors identified susceptible populations for targeted vaccination programs to reduce potential animal losses caused by SBV. [ABSTRACT FROM AUTHOR]

In order to multiply and cause disease a virus must transport its genome from outside the cell into the cytosol, most commonly achieved through the endocytic network. Endosomes transport virus particles to specific cellular destinations and viruses exploit the changing environment of maturing endocytic vesicles as triggers to mediate genome release. Previously we demonstrated that several bunyaviruses, which comprise the largest family of negative sense RNA viruses, require the activity of cellular potassium (K+) channels to cause productive infection. Specifically, we demonstrated a surprising role for K+ channels during virus endosomal trafficking. In this study, we have used the prototype bunyavirus, Bunyamwera virus (BUNV), as a tool to understand why K+ channels are required for progression of these viruses through the endocytic network. We report three major findings: First, the production of a dual fluorescently labelled bunyavirus to visualize virus trafficking in live cells. Second, we show that BUNV traffics through endosomes containing high [K+] and that these K+ ions influence the infectivity of virions. Third, we show that K+ channel inhibition can alter the distribution of K+ across the endosomal system and arrest virus trafficking in endosomes. These data suggest high endosomal [K+] is a critical cue that is required for virus infection, and is controlled by cellular K+ channels resident within the endosome network. This highlights cellular K+ channels as druggable targets to impede virus entry, infection and disease.

Shuni virus is associated with neurologic and febrile illness in animals and humans. To determine potential vectors, we collected mosquitoes in South Africa and detected the virus in species of the genera Mansonia, Culex, Aedes, and Anopheles. These mosquitoes may be associated with Shuni virus outbreaks in Africa and emergence in other regions.

ABSTRACT Ngari virus (NRIV) is a mosquito-borne reassortant orthobunyavirus that causes severe febrile illness and hemorrhagic fever in humans and small ruminants. Due to limited diagnostics and surveillance, NRIV has only been detected sporadically during Rift Valley fever virus outbreaks. Little is known on its interepidemic maintenance and geographic distribution. In this study, sera from cattle, goats, and sheep were collected through a cross-sectional survey after the rainy seasons between 2020 and 2021 in two pastoralist-dominated semiarid ecosystems, Baringo and Kajiado counties in Kenya. NRIV was detected in 11 apparently healthy animals (11/2,039, 0.54%) by RT-PCR and isolated in cell culture from seven individuals. Growth analyses displayed efficient replication in cells from sheep and humans in contrast to weak replication in goat cells. NRIV infection of a wide variety of different vector cells showed only rapid replication in Aedes albopictus cells but not in cells derived from other mosquito species or sandflies. Phylogenetic analyses of complete-coding sequences of L, M, and S segments of four viruses showed that the Kenyan sequences established a monophyletic clade most closely related to a NRIV sequence from a small ruminant from Mauritania. NRIV neutralizing reactivity in cattle, goats, and sheep were 41.6% (95% CI = 30 to 54.3), 52.4% (95% CI = 37.7 to 66.6), and 19% (95% CI = 9.7 to 33.6), respectively. This is the first detection of NRIV in livestock in Kenya. Our results demonstrate active and undetected circulation of NRIV in the three most common livestock species highlighting the need for an active one-health surveillance of host networks, including humans, livestock, and vectors. IMPORTANCE Surveillance of vectors and hosts for infection with zoonotic arthropod-borne viruses is important for early detection and intervention measures to prevent outbreaks. Here, we report the undetected circulation of Ngari virus (NRIV) in apparently healthy cattle, sheep, and goats in Kenya. NRIV is associated with outbreaks of hemorrhagic fever in humans and small ruminants. We demonstrate the isolation of infectious virus from several animals as well as presence of neutralizing antibodies in 38% of the tested animals. Our data indicate active virus circulation and endemicity likely having important implications for human and animal health.

Jamestown Canyon virus (JCV) is a mosquito-borne arbovirus that circulates in North America. We detected JCV in 4 pools of mosquitoes collected from midcoastal Maine, USA, during 2017-2019. Phylogenetic analysis of a JCV sequence obtained from Aedes cantator mosquitoes clustered within clade A, which also circulates in Connecticut, USA. [ABSTRACT FROM AUTHOR]

Background: Akabane virus (AKAV) is a teratogenic and neuropathogenic arbovirus that infects livestock and wild animals. AKAVs are endemic arboviruses from dairy farms in Taiwan in 1989, and the first sequence was detected in cattle with nonsuppurative encephalitis in 1992. Objectives: This study aims to understand the epidemiological relationships of the akabane viruses between Taiwan and nearby places. Methods: In this study, 17 specimens were identified or isolated from vector insects, and ruminant fetuses collected from 1992 to 2015 were sequenced and analysed. Results: Sequence analyses revealed all Taiwanese AKAVs belonged to genogroup Ia but diverged into two clusters in the phylogenetic trees, implying that at least two invasive events of AKAV may have occurred in Taiwan. Conclusions: The two clusters of AKAVs could still be identified in Taiwan in 2015, and a reassortment event was observed, indicating that the two clusters of AKAVs are already endemic in Taiwan. [ABSTRACT FROM AUTHOR]

The Cat Que orthobunyavirus has been found in mosquitoes, birds, pigs, and humans, suggesting its wide range of hosts and potential public health implications. During arbovirus surveillance in 2013, the HN1304M virus was isolated from naturally occurring Culicoides biting midges in Hunan Province, southern China. The virus was cytopathic to BHK-21 cells and showed stable passage, but was not cytopathic to C6/36 cells. Determination and analysis of the viral genome sequence revealed that HN1304M is an RNA virus with three gene segments, namely, L, M, and S. The nucleotide and amino acid sequence homologies of HN1304M to Cat Que viruses in the Manzanilla species complex were 90.3–99.4%, and 95–100%, respectively, while the homologies to other viruses in this species complex were 74–86.6% and 78.1–96.1%, respectively. A phylogenetic analysis of the viral genes revealed that HN1304M formed an evolutionary branch with other Cat Que viruses isolated from mosquitoes, pigs, birds, and humans, which was completely independent of the other viruses in this complex. The fact that the Cat Que virus was isolated from Culicoides suggests that biting midges may participate in the natural circulation of Cat Que viruses. [ABSTRACT FROM AUTHOR]

Objectives: To assess the frequency of symptoms in patients with Oropouche fever and compare them with those observed in patients with dengue and other arboviral diseases., Methods: A systematic review was conducted following the MOOSE and PRISMA reporting guidelines. The review included studies on acute clinical manifestations in patients with Oropouche fever. Searches were conducted in PubMed, Virtual Health Library, Cochrane Library, and Google Scholar up to September 2024. The symptoms of Oropouche fever were compared to those of dengue and other arboviral diseases. Certainty of evidence was assessed using the GRADE approach., Results: A total of 23 studies covering 3648 patients with Oropouche fever were included. The most frequent symptoms in patients with Oropouche virus infection were fever (97%) and headache (86%). There was no difference in frequency of fever or headache between patients with Oropouche and dengue. However, odynophagia (28%) and abdominal pain (15%) were more frequent in Oropouche than in dengue, with odds ratios (ORs) of 3.20 and 2.50, respectively. Myalgia (69%) and arthralgia (57%) were less frequent in Oropouche fever than in dengue., Conclusions: Fever and headache are common in Oropouche virus infection, but do not help discriminate it from dengue. However, odynophagia and abdominal pain are more frequent in patients with Oropouche fever, while myalgia, arthralgia, and rash are more prevalent in dengue. These findings may aid in differential diagnosis in areas of arboviral co-circulation. Further studies on the recurrence and duration of symptoms are needed to improve diagnostic strategies., Competing Interests: Conflictos de intereses. Ninguno declarado.

Peribunyavirids produce enveloped virions with three negative-sense RNA segments comprising 10.7-12.5 kb in total. The family includes globally distributed viruses in multiple genera. While most peribunyavirids are maintained in geographically restricted vertebrate-arthropod transmission cycles, others are arthropod-specific or do not have a known vector. Arthropods can be persistently infected. Human and other vertebrate animal infections occur through blood feeding by an infected vector arthropod, resulting in diverse human and veterinary clinical outcomes in a strain-specific manner. Reassortment can occur between members of the same genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Peribunyaviridae , which is available at ictv.global/report/peribunyaviridae.

Bunyamwera virus (BUNV) is the prototypical member of the Bunyamwera serogroup within the Orthobunyvirus genus. BUNV is transmitted by mosquito vectors of the genera Culex , Aedes and Anopheles and has historically circulated in East Africa, though the transmission has been observed in Argentina. BUNV has been identified as an agent of human and animal disease and has also been misdiagnosed as other agents. BUNV is often thought to be an agent of mild febrile illness in humans, though it can cause abortions in ruminants and neurological disease in horses. Joint pain and gastritis have also been attributed to BUNV. There are limited data concerning the possible spectrum of disease and extent of pathogenesis of BUNV infection, and there are currently no therapeutics or vaccines available. Furthermore, options for animal models for Orthobunyaviruses in general - of which BUNV is the prototypical member - are limited. Eight mice deficient in the type I interferon response were infected with BUNV, and all developed overt disease. All mice developed detectable viraemia and clinical signs, including weight loss, hunched posture and lethargy. Three of the eight mice developed severe diseases, including vascular necrosis and necrosis in the liver, lungs, reproductive organs, bone marrow and spleen, as well as haemorrhages ( n =1) and severe diffuse facial oedema ( n =3), reminiscent of the pathology of Schmallenberg and the Arenaviruses Lassa and Lujo viruses. Thus, BUNV infection of IRF3/7 DKO mice could serve as a BSL-2 model for severe diseases of higher-risk group viruses, which often must be studied at BSL-4. Additionally, our results suggest that BUNV may have the ability to cause severe disease in immunocompromised hosts. Thus, further investigation into the potential spectrum of pathogenesis due to BUNV is important to prioritize for outbreak response, diagnostics and the development of countermeasures.

Oropouche virus has recently caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic. This geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents to the Americas. We review information on Oropouche virus, factors influencing its spread, transmission risk in the United States, and current status of public health response tools. On the basis of available data, the risk for sustained local transmission in the continental United States is considered low because of differences in vector ecology and in human-vector interactions when compared with Oropouche virus-endemic areas. However, more information is needed about the drivers for the current outbreak to clarify the risk for further expansion of this virus. Timely detection and control of this emerging pathogen should be prioritized to mitigate disease burden and stop its spread.

We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4-5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease.

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.

Fort Sherman virus (FSV) was isolated in Panama in 1985 from a US soldier. We report a case of human FSV infection in a febrile patient from northern coastal Peru in 2020. FSV infections spanning ≈35 years and a distance of 2,000 km warrant diagnostics, genomic surveillance, and investigation of transmission cycles.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

We assessed the spatiotemporal dynamics of Oropouche fever in Brazil during 2015-2024. We found the number of cases substantially increased during that period, particularly in the Amazon region. Our findings underscore the need for improved surveillance and public health measures in response to the disease's potential spread beyond endemic areas.

Competing Interests: This work was supported by the Italian Ministry of Health Fondi Ricerca corrente–L1P3, paid to Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore Don Calabria Hospital; Fondi 5 per mille 2021 (project number 5M-2021–23684029); and EU funding within the National Recovery and Resilience Plan, Italian Ministry of University–NextGenerationEU extended partnership initiative on emerging infectious diseases (project number PE00000007 INF-ACT). We declare no competing interests. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps.

Competing Interests: We declare no competing interests. This study did not receive any funding. RM, VA, and AJRM contributed equally.

Not required for Clinical Insight., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)