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PubMed2025

Using homologous network to identify reassortment risk in H5Nx avian influenza viruses.

The resurgence of H5Nx reassortment has caused multiple epidemics resulting in severe disease even death in wild birds and poultry. Assessing H5Nx reassortment risk is crucial for designing targeted interventions and enhancing preparedness efforts to manage H5Nx outbreaks effectively. However, the complexity in H5Nx reassortment, driven by the diversity of influenza A viruses (IAVs) and wide range of hosts, has hindered the effective quantification of reassortment risk. In this study, we utilized a network approach to explore the reassortment history using a large-scale dataset. By inferring genomic homogeneity among IAVs, we constructed an IAVs homologous network with reassortment history embedded within it. We estimated the communities within the IAVs homologous network to represent the reassortment risk of various viruses, revealing diverse reassortment risks across different H5Nx viruses. Our analysis also identified the primary hosts contributing to reassortment: domestic poultry in China, and wild birds in North America and Europe. These primary hosts are critical targets for future H5Nx reassortment interventions. Our study provides a framework for quantifying and ranking H5Nx reassortment risk, contributing to enhanced preparedness and prevention efforts.

Animals↗

PubMed2026

Host hybridization enabled the emergence of a reassorted hantavirus lineage.

The exchange of genetic material between individuals is a key driver of evolution and diversification across most branches of life. Segmented viruses can exchange genetic material through reassortment of genomic segments. New viral strains that emerge from reassortments can have greater infection ranges and higher virulence, although concrete examples of the adaptive advantages of reassortants in nature apart from influenza remain rare. We studied here the evolutionary history and consequences of reassortment in Tula orthohantavirus (TULV) in a hybrid zone between evolutionary lineages of its reservoir host, the common vole (Microtus arvalis). Across 58 trapping sites and 127 infected voles, we detected 27 TULV reassortants in a 12.5 km broad zone at the contact of the parental TULV clades, resembling a viral hybrid zone concordant with the hosts'. Phylogenomic analyses revealed three independent reassortment events, but most of the host hybrid zone was dominated by a single strain with a reassorted M-Segment, which encodes the surface glycoprotein. We detected clade-specific variation in the glycoprotein's N-terminal region consisting of five residues, two of which showed evidence of positive selection. In silico 3D modeling of seven glycoproteins confirmed that this N-terminal region has a unique and specific structure for each TULV clade and the dominant reassortants and is the only structurally variable region of the TULV glycoprotein. Our findings suggest that reassortment between the parental TULV clades in the contact region has resulted in a transgressive virus phenotype potentially adapted to hybrid hosts. This demonstrates the potential of zones of hybridization for the emergence of new virus strains with novel evolutionary trajectories.

Animals↗

PubMed2025

Probing orthobunyavirus reassortment using Bunyamwera and Batai viruses as models.

Reassortment is a critical evolutionary mechanism for segmented viruses, enabling the exchange of intact genome segments during co-infection and driving orthobunyavirus evolution; however, the molecular mechanisms underpinning this process remain unclear. With over 100 orthobunyavirus species, many of which are significant human and veterinary pathogens, understanding how reassortment influences transmissibility and virulence is essential for preempting the emergence of novel pathogens. Here, we use Bunyamwera virus (BUNV) and Batai virus (BATV) as models to explore orthobunyavirus reassortment through reverse genetics. We established the first reverse genetics system for BATV, generated reassortants, and employed minigenome assays to assess replication machinery compatibility. Additionally, we developed a novel hybridization chain reaction assay for high-resolution visualization of viral RNA segments. Our findings revealed that all six reassortants between BUNV and BATV are viable, exhibiting notable phenotypic differences in interferon-deficient (IFNAR-/-) mice. This work introduces essential tools and new insights into orthobunyavirus reassortment and pathogenesis, laying the groundwork for understanding this critical evolutionary process.

Animals↗

PubMed2026

Genomic and Clinicopathological Characterization of a Reassortant HPAI H5N1 (Clade 2.3.4.4b) in an Endangered Cinereous Vulture (Aegypius monachus) in South Korea, 2026.

Clade 2.3.4.4b highly pathogenic avian influenza viruses (HPAIVs) continue to circulate widely in East Asia and undergo frequent reassortment in wild birds. Raptors are regarded as spillover hosts that may be exposed through predation or scavenging, yet integrated clinicopathologic and genomic investigations in cinereous vultures remain limited. Here, we describe a fatal H5N1 HPAIV infection in a cinereous vulture (Aegypius monachus) found in South Korea on January 17, 2026. On presentation, the cinereous vulture showed severe neurologic dysfunction, including inability to stand, right-sided head tilt with pathologic nystagmus, reduced oculocephalic and palpebral reflexes, and intermittent bilateral leg tremors. The cinereous vulture died within 2 days after rescue, and a complete necropsy was performed. Hematologic and biochemical testing revealed marked heterophil predominance, severe lymphopenia, mild monocytosis, and globulin values near the upper end of the reference interval. An oropharyngeal swab tested positive for influenza A virus, and a virus isolate, designated A/Cinereous_Vulture/Korea/26-JBN47/2026(H5N1), was recovered in embryonated chicken eggs. Histopathology showed nonsuppurative encephalitis and necrotizing myocarditis, and influenza A nucleoprotein was detected immunohistochemically in neurons and cardiomyocytes. Tissue real-time RT-PCR showed the lowest cycle threshold value in the brain. Whole-genome sequencing demonstrated that 26-JBN47 belonged to clade 2.3.4.4b and contained a polybasic HA cleavage site (PLREKRRKR/GLF). Segment-level phylogenetic analysis revealed a reassortant genome constellation comprising a maintained H5N1 backbone in HA, NA, and M; low PAIV (LPAIV)-associated but H5N1-incorporated PA and NP segments; flyway-associated PB2 and NS segments; and a PB1 segment phylogenetically linked to regional LPAIV lineages. Molecular marker analysis identified multiple substitutions previously reported to be associated with receptor-binding properties, polymerase-related fitness, virulence, and host-response modulation, whereas canonical PB2 mammalian-adaptive markers were absent. These findings show that 26-JBN47 was a reassortant clade 2.3.4.4b H5N1 HPAIV associated with systemic disease and clinicopathological findings consistent with neurotropic and cardiotropic infection in a cinereous vulture. They also support the potential value of scavenging raptors as sentinels of local or regional HPAIV circulation involving reassortant viruses in East Asia.

Animals↗

PubMed2026

Reassortment of Highly Pathogenic Avian Influenza as a Driver for Zoonotic Spillover, Asia.

Highly pathogenic avian influenza H5Nx viruses remain a major zoonotic threat, yet global attention has focused largely on clade 2.3.4.4b, potentially overlooking major changes within long-endemic H5N1 lineages in Asia. Recent reports from South and Southeast Asia describe the emergence of reassortant clade 2.3.2.1 viruses alongside renewed human infections after apparent prolonged epidemiologic stability. Collectively, those events suggest a regional pattern rather than isolated anomalies. In this article, we argue that reassortment, rather than point mutation alone, might be an underrecognized driver of zoonotic risk in endemic H5N1 lineages and is reshaping those lineages. We examine why such events might be underrecognized in settings with entrenched poultry influenza, identify limitations of current surveillance systems, and call for integrated, real-time approaches linking genomic detection with phenotypic assessment across animal and human health sectors to enable timely risk assessment and coordinated public health action.

Asia↗

PubMed2026

Genetic and pathogenic characterization of a novel infectious bursal disease virus field strain with natural reassortant and recombinant features from southern China.

NN040124 is a novel field-derived IBDV strain (vv-A/att-B) exhibiting both reassortment and recombination events.Infection with NN040124 causes 40% mortality and severe lymphoid depletion in three-yellow chickens.These findings demonstrate the pivotal role of the N-terminal domain of segment B in IBDV pathogenicity and virulence.

A3B1a↗

PubMed2025

Orthobunyavirus neurovirulence is a complex trait involving all three genome segments.

La Crosse orthobunyavirus (LACV) is a tri-segmented negative sense RNA virus and is the leading cause of pediatric arboviral encephalitis in the USA. The viral factors that mediate LACV's ability to replicate and cause damage and disease in the brain (neurovirulence) are not fully understood. We previously characterized the neurovirulence of LACV and closely related Inkoo virus (INKV) and discovered they have opposing neurovirulence phenotypes in mice and human neuronal cells: LACV has high neurovirulence and INKV has low neurovirulence. We therefore generated reassortant viruses between LACV and INKV to map the genome segments that mediate LACV's high neurovirulence phenotype. We recovered all six possible reassortant viruses of the L, M, and S genome segments using coinfection and reverse genetics approaches. We evaluated the neurovirulence of these reassortant viruses in mice in vivo and in human neuronal cells in vitro. Our results show that no single LACV genome segment alone was sufficient to cause wildtype LACV-like neurological disease in mice, and in fact all six reassortant viruses were attenuated from wildtype LACV. We found that the LACV M and S segments together were the primary drivers of neurological disease in mice, whereas the LACV L segment played a minor role. Our in vitro results indicate that the LACV M segment is crucial for efficient replication in neurons, but the LACV L segment appears to mediate slightly more efficient neuronal replication than the INKV L segment. The LACV M and S segments together induced wildtype LACV-like levels of neuronal death, indicating the LACV M and S are the primary mediators of neuronal death, and the L segment is not required. Together, these results indicate that LACV neurovirulence is a complex trait mediated by viral proteins on all three genome segments.

Journal Article↗

PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗

PubMed2026

Molecular Pathogenesis, Global Epidemiological Trends, and Treatment Strategies for Pteropine Orthoreoviruses: A Narrative Review.

Pteropine orthoreoviruses are emerging bat-borne zoonotic viruses of the genus Orthoreovirus (family Reoviridae), increasingly recognized as causes of acute respiratory disease in humans. Originally grouped with the largely non-pathogenic mammalian orthoreoviruses, they have challenged that view through their association with severe influenza-like illness, evidence of human-to-human transmission, and a broad geographic range across the Old World. Maintained primarily in fruit bats of the family Pteropodidae, they are now linked to neurological as well as respiratory disease. This narrative review synthesizes current knowledge of their molecular pathogenesis, zoonotic ecology, and global epidemiology, integrating recent advances in phylogeography, reassortment-driven evolution, spillover dynamics, and translational biomedical applications within a unified One Health framework. Genomic diversity, reassortment potential, and the unique fusion-associated small transmembrane proteins together underpin viral adaptability and pathogenicity. Major gaps nonetheless remain in transmission dynamics, host adaptation, shedding ecology, and pandemic potential. Future priorities should include integrated genomic surveillance, improved diagnostic strategies, validated experimental models, and interdisciplinary One Health approaches to strengthen outbreak preparedness and prevention.

Bat-borne viruses↗

PubMed2026

Genomic characteristics and tracing analysis of an acute gastroenteritis outbreak associated with rotavirus C in a boarding high school.

BACKGROUND: Rotaviruses are major pathogens of childhood acute gastroenteritis, dominated by rotavirus A (RVA). Outbreaks caused by human rotavirus C (RVC) are rarely reported, and relevant genomic data remain scarce. This genomic investigation of an RVC outbreak improves our understanding of viral diversity and transmission dynamics. METHODS: We performed epidemiological surveys, nucleic acid testing and whole-genome sequencing (WGS) on specimens from a 2025 RVC-associated gastroenteritis outbreak at a Chinese boarding high school. Sequence alignment, phylogenetic and molecular tracing analyses were conducted to explore RVC evolution via point mutation, segment reassortment and genomic recombination. RESULTS: This typical point-source campus outbreak was linked to an indoor student gathering matching the incubation period of RVC. Thirteen RVC FX strains were recovered from 11 rectal swabs and two vomitus samples. Their viral protein (VP) 4 and VP7 sequences shared high homology with Russian reference strains, carrying distinct amino acid variations. No segment reassortment or recombination was detected in VP4/VP7 genes. CONCLUSIONS: Dense, closed campus settings facilitate RVC clustered transmission. Limitations included absent screening of asymptomatic canteen staff. Rapid nucleic acid testing enabled timely pathogen identification for outbreak control. Greater attention should be paid to the public health risk of RVC. These whole-genome sequencing data enrich resources for studying RVC evolution and vaccine development.

Acute gastroenteritis outbreak↗

PubMed2024

Expansion of Oropouche virus in non-endemic Brazilian regions: analysis of genomic characterisation and ecological drivers.

BACKGROUND: Oropouche virus (OROV) is an arbovirus endemic in the Amazon region that closely resembles other arboviruses in terms of human disease, leading to potential misdiagnoses. The virus ecology has mostly restricted its occurrence to the Amazon biome; however, after a large 2023-24 OROV epidemic in the Brazilian Amazon region, outbreaks are being reported across Brazil and in other countries in Latin America. Here, we investigate the OROV spread outside Amazonia. METHODS: In this genomic and epidemiological study, OROV cases from January, 2023, to July, 2024, provided by the General Coordination of Public Health Laboratories of Brazil on Aug 1, 2024, were compared by geographical location (Amazon vs non-Amazon) and municipal population size, and a linear mixed model was employed to assess the relationship between agricultural area size and cases. OROV-positive samples from central laboratories of five non-Amazonian Brazilian states were sequenced using an amplicon-based approach. Bayesian phylogeographical analysis was performed with near full-length viral genomes, incorporating individual travel histories when relevant. The estimated dates of viral introductions in each sampled location were then contextualised with public epidemiological data. FINDINGS: Epidemic data show that outside the Amazon region, OROV cases frequency was 3·9-times higher in small municipalities than in large municipalities. The planted areas of some agricultural products, such as banana plantations, were positively correlated (r=0·39, p<0·0001) with OROV cases. The linear mixed model revealed that, besides banana, cassava also has larger (p<0·05) planted areas in municipalities with OROV cases when compared with those with no cases. The phylogenetic analysis of 32 new OROV genomes reconstructed multiple exportation events of the newly identified reassortant lineage from the Amazon to other Brazilian regions between January and March, 2024. At least three of the previously described OROV phylogenetic clades circulating in the Amazon were the source of viral introductions. Molecular clock analysis estimated that viral introductions happened from 50 days to 100 days before detecting the outbreaks in each state. INTERPRETATION: Our results confirm that the novel OROV reassortant lineage spread from the Amazon to other regions in early 2024, successfully establishing local transmission. The fact that outbreaks were observed in small municipalities, instead of large urban centres, suggests that local ecological conditions that are ideal for OROV vector occurrence, such as the banana plantation environment, might be important factors driving its spread in Brazil. FUNDING: DECIT, CNPq, FAPEAM, and Inova-Fiocruz. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Brazil↗

PubMed2025

Phylogenetic and Genetic Evolution Analysis of Complete SFTSV Genome Sequences in Shandong Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV). Shandong province is one of the epidemic regions with high incidence rate of SFTS. To investigate phylogenetical and genetic evolution characteristics of SFTSV in Shandong province, we isolated SFTSV from suspected patients between April 2023 and October 2024, and then whole SFTSV genomes were amplified and sequenced in this study. A total of 25 new strains were analyzed together 56 strains submitted in Genbank from Shandong province. Phylogenetical and genetic analyses of the data set revealed that four genotypes were co-circulating in Shandong province. C3 genotype was the most common genotype in each year with lower genetic divergence. 298 amino acid substitutions were detected in the four proteins of SFTSV, but only two substitutions (Arg624Lys and Arg962Ser) had been proven to have potential impacts on biological functions. In addition, one reassortment strain (C3/C4/C4 for L, M and S segments) and three recombinant strains were identified. Analysis of selection pressure at the level of amino acid substitutions indicated genes within the four ORFs of SFTSV were all subjected to negative selection. In conclusion, the genetic characteristics and evolutionary mechanism of SFTSV was complex in Shandong province. It is necessary to conduct continuous surveillance to grasp the genetic evolution patterns, and to discover novel prevalent variants in a timely manner.

China↗

PubMed2026

Spatiotemporal patterns of Rift Valley fever virus in Africa: a retrospective genomic epidemiology and phylodynamic modelling study.

BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing outbreaks in humans and ruminants across Africa and the Arabian Peninsula. Originally restricted to the Great Rift Valley, RVFV has expanded geographically, prompting its classification by WHO as a pathogen of pandemic potential. We investigated the evolutionary and spatial dynamics of RVFV across Africa. METHODS: We used genomic data generated at the International Livestock Research Institute Nairobi genomic laboratory (BioProject PRJNA1106221) and combined with publicly available datasets retrieved from the National Center for Biotechnology (NCBI) GenBank nucleotide database. In retrieving RVFV genome sequences from the NCBI GenBank, we applied the search terms "Rift Valley fever virus segment L AND 6404[SLEN]", "Rift Valley fever virus segment M AND 3885[SLEN]", and "Rift Valley fever virus segment S AND 1520:1690[SLEN]" for L (Large), M (Medium), and S (Small) segments, respectively. For sequences without additional spatiotemporal information, we searched PubMed to extract the associated sequence metadata. We performed molecular clock analysis, phylogenetic inference, phylodynamic modelling (continuous phylogeographic reconstruction), and landscape phylogeography on the three RVFV genome segments (L, M, and S). We aimed to assess evolutionary rates, dispersal patterns, and environmental drivers. Focus was placed on lineage C, the most widely distributed variant. FINDINGS: The global dataset used in this study consisted of large (n=236), medium (n=237), and small (n=247), which were further filtered to exclude potential reassortants and vaccine strains. Genome sequences retrieved from NCBI GenBank database comprised large (n=180), medium (n=184), and small (n=202). The genome sequences from retrospective human and livestock isolates comprised large (n=56), medium (n=53), and small (n=45) collected in Burundi (2018), Kenya (2007, 2018, 2019, 2021, and 2022), and Rwanda (2018 and 2022). Our dataset revealed that RVFV exhibited low overall genetic diversity. Lineage C, however, showed evidence of active evolution, with substitution rates ranging from 3·58 × 10-4 to 9·76 × 10-4 substitutions per site per year. This lineage probably originated in Zimbabwe in the mid-1970s and has since expanded across eastern and southern Africa. Phylogeographic reconstructions revealed rapid spread, with diffusion coefficients exceeding 50 000 km2 per year. INTERPRETATION: Lineage C appears capable of establishing endemic transmission in new regions, with ongoing diversification observed during interepidemic periods. These observations reinforce the value of continuous genomic surveillance, particularly during cryptic transmission phases when adaptive mutations might emerge. Although further evidence is needed, observed trends in climate variability and land-use change point to the potential benefit of targeted surveillance in settings that could be at increased risk, including urban centres and wetlands. FUNDING: This work was supported by the German Federal Ministry for Economic Cooperation and Development, the Rockefeller Foundation, and the Africa Centres for Disease Control and Prevention.

Rift Valley fever virus↗

PubMed2026

Safety, humoral and cellular immune responses to a pre-pandemic adjuvanted influenza A (H5N8) vaccine.

Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.

H5N8 influenza vaccine↗

PubMed2026

Immunogenicity and efficacy of a rabies-based vaccine against highly pathogenic influenza H5N1 virus.

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV and H5N1 Influenza virus and protected mice from a lethal challenge with PR8 recombinants reassorted with the HA of clade 1 (Viet Nam 1203) or clade 2.3.4.4b HPAI-H5N1 viruses, highlighting its potential use in mitigating the risk of HPAI-H5N1 pandemic.

Influenza A Virus, H5N1 Subtype↗

PubMed2026

Identification and full genome sequencing of previously unknown sandfly-borne phleboviruses using a newly established capture-based next-generation sequencing approach.

Sandfly-borne phleboviruses cause febrile illness and neuroinvasive disease in humans. While infections are reported in the Mediterranean region, the discovery of previously unknown phleboviruses in sandflies from Kenya suggests a wider geographic distribution. Detection and characterization of novel phleboviruses are often hindered by low-quality and low-viral-load samples. We developed a capture-based target enrichment next-generation sequencing approach that showed a 99%-100% fold enrichment of viral genomes from primary material and provides a robust tool for generating complete genomes of both known and previously unknown viruses. From a collection of 15,652 sandflies in Kenya, we recovered seven complete coding sequences of Embossos, Bogoria, and Kiborgoch viruses, and of two previously unknown phleboviruses, which were named Sosoik and Shable viruses. Sosoik virus shared 83% amino acid identity in its RdRp gene with that of Bogoria virus, while Shable virus shared ca. 88% amino acid identity with viruses of the Salehabad serocomplex. Additionally, a reassortant of Shable virus was detected that possessed an M segment from an undescribed Ponticelli-like virus. DNA barcoding of blood-fed sandflies revealed several potentially novel Sergentomyia species and evidence of host-feeding on humans, livestock, and reptiles, suggesting possibilities for zoonotic transmission. Overall, our findings increase the known genetic diversity of Old World sandfly-borne phlebovirus species from 18 to 25 (by 38.9%), including the detection of viruses from all pathogenic sandfly-borne phlebovirus serocomplexes in East Africa, opening new horizons in disease ecology research.IMPORTANCEKnowledge of the genetic diversity of circulating pathogens is crucial for providing appropriate diagnostics and disease management. This study established a novel capture-based target enrichment next-generation sequencing approach that enabled the near-complete viral genome recovery from primary samples, while native NGS yielded negative or poor-quality results. In addition to the five recently discovered sandfly-borne phleboviruses in Kenya, two previously unknown phleboviruses were detected in sandflies from the same region. The viruses were detected in several sandfly species, which showed diverse host-feeding behaviors, including mixed feeding on humans and chickens. The study significantly advances the understanding of sandfly-borne phleboviruses by uncovering their broader geographic distribution and genetic diversity, particularly in East Africa, highlighting the importance of expanding surveillance efforts beyond traditionally studied regions.

Phlebovirus↗

PubMed2025

Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.

Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known. Less is known about antiviral mechanisms that suppress IAV zoonoses. We observed CpG dinucleotide depletion in human IAV relative to avian IAV. Notably, human ZAP selectively depletes CpG-enriched viral RNAs with its cofactor KHNYN. ZAP is conserved in tetrapods, but we uncovered that avian species lack KHNYN. We found that chicken ZAP may not affect IAV (PR8) or CpG-enriched IAV (PR8CG). Human ZAP or KHNYN independently restricted CpG-enriched IAV PR8CG by overexpression in chicken cells and by combined knockout in human cells. Additionally, mammalian ZAP-L and KHNYN also independently restricted an avian retrovirus (ROSV). Curiously, platypus KHNYN, the most divergent from eutherian mammals, was also capable of independent restriction of multiple diverse viruses. We suggest that some mammalian KHNYN can act as a bona fide restriction factor with cell-autonomous activity. Furthermore, we speculate that through repeated contact between avian viruses and mammalian hosts, protein changes may accompany CpG-biased mutations or reassortment to evade mammalian ZAP and KHNYN.

Animals↗

PubMed2025

Clinical and laboratory profiles of Oropouche virus disease from the 2024 outbreak in Manaus, Brazilian Amazon.

BACKGROUND: The 2024 Oropouche virus (OROV) outbreak in Brazil raised public health concerns due to its unprecedented rapid spread, high incidence, and potential neurological complications. OROV symptoms overlap with locally endemic arbovirus diseases, like dengue virus (DENV), complicating diagnosis. The study aimed to compare clinical, laboratory, and immunological profiles in OROV and DENV cases, crucial for improving diagnosis and management. METHODS: This study analyzed 51 OROV and 78 of DENV cases consecutively enrolled in Manaus, Amazonas, Brazil, and monitored for 28 days. OROV diagnosis was performed by real-time PCR (RT-PCR) using serum and urine samples. OROV RT-PCR positive samples were genotyped. A paired Plaque Reduction Neutralization Test (PRNT) was conducted on samples collected at D1 and D28. Patients with a ≥ 4-fold increase in neutralizing antibody titer between D1 and D28 were considered OROV-positive. Clinical manifestations, hematology, biochemistry, and cytokine profiles were analyzed. Statistical analysis included comparison between OROV and DENV patients. RESULTS: Genome sequencing of OROV isolates confirmed presence of a previously reported novel reassortment event, consistent with ongoing localized transmission. Urine RT-PCR demonstrated low positivity compared to serum samples. The paired PRNT increased sensitivity in 45%. Clinically, OROV infection was associated with significantly higher frequencies of severe headache, myalgia, arthralgia, and rash compared to DENV infection (p < 0.001). Elevated alanine aminotransferase (ALT) levels were also observed in OROV patients (p < 0.001). Immunologically, OROV infection induced significantly increased levels of acute-phase CCL11 (eotaxin), CXCL10, IFN-γ, IL-1RA, and IL-10, which declined by day 28, while IL-5 increased during recovery. In contrast, DENV patients exhibited elevated levels of CCL2, G-CSF, and CCL3 in recovery phase. CONCLUSION: OROV symptoms overlap with DENV underscores the need for syndromic diagnostic approach in endemic regions. Continued genomic surveillance and expanded clinical studies are vital to assess long-term consequences. Given OROV's expanding geographic range, targeted public health measures are essential to mitigate future outbreaks and better understand its pathophysiology.

Humans↗