Search Results (173)

The Crimean–Congo hemorrhagic fever virus (CCHFV) is a single-stranded, segmented RNA virus belonging to the Nairoviridae family, and it is rapidly expanding across Africa, Asia, and southern Europe, probably favored by climate change and livestock trade. Its fatality rate in humans reaches up to 40%, and there is currently no specific treatment or vaccine available. Therefore, the development of therapies against CCHFV is essential, and their design requires understanding of the molecular evolution and genetic distribution of the virus. Motivated by these concerns, we present a comprehensive review of the molecular evolution, genetic characterization, and phylogeography of CCHFV, and we discuss their potential implications for therapeutic design. Specifically, we describe the virus’s capacity to increase its genetic diversity through numerous mutations, recombination events, and genomic reassortments, which affect fundamental viral functions such as RNA binding, host–virus interactions, viral entry, and polymerase activity. We also assess the presence of temporal heterogeneous rates of evolution and molecular adaptation among CCHFV coding regions, where purifying selection is generally predominant but diversifying selection is observed in molecular regions associated with host adaptation and transmission. We emphasize the importance of understanding the complex molecular evolution of CCHFV for the rational design of therapies and highlight the need for efforts in surveillance, evolutionary prediction, and therapeutic development. Full article

Influenza A virus (IAV) is a highly diverse pathogen with genetic variability primarily driven by mutation and reassortment. Using next-generation sequencing (NGS), we characterised defective viral genomes (DVGs) generated during the serial passaging of influenza A/Puerto Rico/8/1934 (H1N1) virus in embryonated chicken eggs. Deletions were the most abundant DVG type, predominantly accumulating in the polymerase-encoding segments. Notably, we identified and validated a novel class of multisegment DVGs arising from intersegment recombination events, providing evidence that the IAV RNA polymerase can detach from one genomic template and resume synthesis on another. Multisegment recombination primarily involved segments 1–3 but also occurred between other segment pairings. In specific lineages, certain multisegment DVGs reached high frequencies and persisted through multiple passages, suggesting they are not transient by-products of recombination but may possess features that support stable maintenance. Furthermore, multisegment DVGs were shown to be encapsidated within virions, similar to deletion DVGs. The observation of recombination between segments with limited sequence homology underscores the potential for complex recombination to expand IAV genetic diversity. These findings suggest recombination-driven DVGs represent a previously underappreciated mechanism in influenza virus evolution. Full article

A characteristic feature of influenza A viruses is their high capacity for reassortment, significantly increasing their genetic diversity. This can lead to the formation of influenza A virus variants with unique phenotypic characteristics, particularly those with pandemic potential. Representatives of the H4N9 subtype are low-pathogenic influenza A (LPAI) viruses. Despite their low pandemic potential, these viruses may represent an important reservoir of genes for genetic exchange with other IAVs. Here, we analyzed the reassortment events of H4N9 viruses using all publicly available sequences. Several computational approaches, including phylogenetic reconstructions and reassortment detection algorithms (PDDM and PDCP), were used to identify phylogenetic incongruences. Numerous reassortment events were detected in H4N9 viruses, especially in the NS segment. This suggests extensive genetic exchange with other avian and mammalian IAVs. In addition, a comparison of phylogenetic and geographic patterns suggests that H4N9 viruses have undergone multiple trans-regional transmissions. These results suggest that LPAI viruses make a significant contribution to the overall influenza gene pool, increasing the likelihood of the emergence of new IAV variants with unpredictable phenotypic characteristics. However, our results suggest that the current understanding of the real distribution and genetic diversity is fragmented. Therefore, better monitoring and surveillance of H4N9 viruses should improve influenza pandemic preparedness. Full article

Low pathogenic H9N2 avian influenza viruses have become widespread in wild birds and poultry worldwide, raising concerns about their potential to spark pandemics or their role in enhancing the virulence and infectivity of H5Nx viruses through genetic reassortment. Therefore, influenza monitoring studies, including those of H9N2 viruses, are crucial for understanding, evaluating, and mitigating the risks associated with avian infections, and have broader implications for global public health. Although H9N2 viruses are not considered enzootic in Kazakhstan, they have been repeatedly detected in wild waterfowls and domestic poultry. In this study, all eight gene segments of influenza A/H9N2 viruses isolated in various regions of Kazakhstan between 2014 and 2020 were sequenced and analyzed. Molecular characterization revealed the presence of genetic markers associated with mammalian infectivity and disease potential. Furthermore, their predicted receptor binding site sequences indicate their potential capacity to attach to human-type receptors. These findings highlight the importance of continued surveillance and molecular investigation to better understand the evolution and zoonotic potential of H9N2 viruses in Kazakhstan. Full article

Rotavirus alphagastroenteritidis is the leading cause of acute gastroenteritis worldwide in young humans and animals. In 2023–2024, a relatively high rotavirus detection rate (34.5%) was detected in children with diarrhea in Caracas. All rotavirus strains were typed as P[8], using a multiplex RT-PCR assay, while the G-type was not identified. This unusual pattern, not previously observed in Venezuela, prompted the VP7 gene sequencing of nineteen strains, which displayed a high sequence identity (99.3–100%) compatible with the G3 genotype. These strains clustered into a well-supported lineage IX encompassing human reassortants of equine-like G3P[8] strains described elsewhere, showing a very close genetic relationship (99.0–99.9%). Old G3 rotavirus isolates obtained from diarrheic samples in the past were included in the analysis and grouped into lineage I together with ancestral reference G3 strains. The novel G3P[8]s carry amino acid changes in VP7-neutralizing epitopes, compared with the RotaTeq-WI78-8-vaccine strain. Full genome sequencing of a representative strain revealed a genotype constellation including an equine-like G3P[8] in a DS-1-like backbone (I2–R2–C2–M2–A2–N2–T2–E2–H2), confirming the role of animal strains as a source of diversification, and the importance of unceasingly revising molecular typing strategies and vaccine efficacy to guarantee their success. Full article

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic disease within the genus Phlebovirus. Symptoms of the disease in animals range from moderate to severe febrile illness, which significantly impacts the livestock industry and causes severe health complications in humans. Similar to bunyaviruses in the genus Orthobunyavirus transmitted by mosquitoes, RVFV progression is dependent on the susceptibility of the physical, cellular, microbial, and immune response barriers of the vectors. These barriers, shaped by the genetic makeup of the mosquito species and the surrounding environmental temperature, exert strong selective pressure on the virus, affecting its replication, evolution, and spread. The changing climate coupled with the aforementioned bottlenecks are significant drivers of RVF epidemics and expansion into previously nonendemic areas. Despite the link between microclimatic changes and RVF outbreaks, there is still a dearth of knowledge on how these temperature effects impact RVF transmission and vector competence and virus persistence during interepidemic years. This intricate interdependence between the virus, larval habitat temperatures, and vector competence necessitates increased efforts in addressing RVFV disease burden. This review highlights recent advancements made in response to shifting demographics, weather patterns, and conveyance of RVFV. Additionally, ongoing studies related to temperature-sensitive variations in RVFV–vector interactions and knowledge gaps are discussed. Full article

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever. Full article

Rotavirus A (RVA) is the primary enteric pathogen of humans and many other species. However, RVA interspecies transmission remains poorly understood. In this study, we conducted a comprehensive screening and genotyping analysis of RVA in 1706 wild animal samples collected from various regions within Yunnan Province, China. A total of 24 samples, originating from wild boars, rodents, bats, and birds tested positive for RVA. Next generation sequencing and phylogenetic analyses revealed a high degree of genetic diversity and reassortment, particularly for VP4 and VP7. Strains isolated from wild boars and rodents exhibited gene segments with high similarity to those found in humans and other mammalian RVA strains, indicating that RVA may undergo interspecies transmission and reassortment, resulting in novel strains with potential risks for human infection. This study provides critical data for understanding the transmission mechanisms and the RVA host range, and highlights the pivotal role of wildlife in viral evolution and dissemination. These findings have significant implications for public health policies and emphasize the need for enhanced surveillance to prevent interspecies RVA transmission. Full article

Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are vector-borne orbiviruses that pose an emerging threat to livestock, including cattle and sheep. This review summarizes the global distribution, genetic diversity, and key factors driving their spread along with the existing knowledge gaps and recommendations to mitigate their impact. Both viruses cause hemorrhagic disease in susceptible ruminants and are commonly reported in tropical and subtropical regions including North America, Asia, Africa, Oceania, and some parts of Europe. The geographical distribution of these viruses, encompassing 27 BTV and 7 EHDV serotypes, has shifted, particularly with the recent invasion of BTV-3, 4, and 8 and EHDV-8 serotypes in Europe. Several factors contribute to the recent spread of these viruses such as the distribution of virulent strains by the movement of temperature-dependent Culicoides vectors into new areas due to rapid climate change, the reassortment of viral strains during mixed infections, and unrestricted global trade. These diseases cause significant economic impacts including morbidity, mortality, reduced production, high management costs, and the disruption of international trade. Effective prevention and control strategies are paramount and rely on vaccination, vector control using insecticides, and the destruction of breeding sites, husbandry practices including the isolation and quarantine of infected hosts, restriction of animal movement, prompt diagnosis and identification of circulating strains, and effective surveillance and monitoring plans such as the pre-export and post-import screening of semen used for artificial insemination. However, challenges remain with intercontinental virus spread, live vaccines, and the failure of inactivated vaccines to produce protective immunity against dissimilar strains. Significant knowledge gaps highlight the need for a better scientific understanding and a strategic plan to ensure healthy livestock and global food security. Full article

Avian influenza subtype H5N1 has caused outbreaks worldwide since 1996, with the emergence of the Guandong lineage in China. The current clade 2.3.4.4b has evolved from this lineage, with increased virulence and mass mortality events in birds and mammals. The objective of this study was the analysis of 17 viral genomes of H5N1 avian influenza isolated in Venezuela during the 2022–2023 outbreak. The eight viral genomic segments were amplified using universal primers and sequenced via next-generation sequencing. The sequences were analyzed to confirm the H5 hemagglutinin clade, identify possible genetic reassortments, and perform a phylogenetic and docking analysis of the viral isolates. The viruses found in Venezuela belonged, as expected, to clade 2.3.4.4b and formed a monophyletic clade with North American influenza viruses, with no evidence of further reassortment. The introduction of the virus in South America is associated with bird migration through the Atlantic (Venezuela), Atlantic/Mississippi (Choco, Colombia), and Pacific migratory flyways, with the emergence of several viral lineages. Several mutations were found in all segments of the genome, although none of the key mutations was involved in mammalian adaptation. Moreover, in silico structural analysis suggests, as expected, that the viral hemagglutinin maintained a predilection for avian α2,3-linked sialic acid. The unprecedented pathogenic outbreak of avian influenza disease in South America was associated with the circulation of three different lineages, which maintain a lower affinity for the mammalian receptor. Full article

Genetically diverse avian influenza viruses (AIVs) are maintained in wild aquatic birds with increasingly frequent spillover into mammals, yet these represent a small proportion of the overall detections. The isolation of AIVs in marine mammals, including seals, has been reported sporadically over the last 45 years. Prior to 2016, all reports of AIVs detected in seals were of low-pathogenicity AIVs. In spite of this, the majority of reported AIV outbreaks caused fatal respiratory diseases, with harbor seals particularly susceptible to infection. The H5 clade 2.3.4.4b highly pathogenic AIV (HPAIV) was detected in seals for the first time in 2016. Recently, many cases of mass seal die-offs have occurred because of 2.3.4.4b HPAIV and are attributed to spillover from wild bird species. The potential for seal-to-seal transmission has been considered after the mass mortality of southern elephant seals off the coast of Argentina. Close contact between seals and wild birds, the rapid evolution of H5N1 AIVs, and the possibility of efficient mammal-to-mammal transmission are increasing concerns due to the potential for the establishment of a marine mammal reservoir and public health risks associated with the pandemic potential of the virus. This manuscript details the detection of AIVs in the seal population, comparing interesting features of various subtypes with an emphasis on avian-to-mammal-to-mammal transmission. Phylogenetic characterizations of the representative seal isolates were performed to demonstrate the relationships within the different virus isolates. Furthermore, we demonstrate that the reassortment events between different LPAIVs occurred before and after the viruses reached the seal population. The reassortment of viral segments plays an important role in the evolution of influenza viruses. Taken together, these data report on the 45 year history between seals and AIVs. Full article

Influenza A viruses (IAVs), which belong to the Orthomyxoviridae family, are RNA viruses characterized by a segmented genome that allows them to evolve and adapt rapidly. These viruses are mainly transmitted by wild waterfowl. In this study, we investigated the evolutionary processes of H7Nx (H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, H7N9) viruses, which pose a significant pandemic risk due to the known cases of human infection and their potential for rapid genetic evolution and reassortment. The complete genome sequences of H7Nx influenza viruses (n = 3239) were compared between each other to investigate their phylogenetic relationships and reassortment patterns. For the selected viruses, phylogenetic trees were constructed for eight genome segments (PB2, PB1, PA, HA, NP, NA, M, NS) to assess the genetic diversity and geographic distribution of these viruses. Distinct phylogenetic clades with remarkable geographic patterns were found for the different segments. While the viruses were consistently grouped by subtype based on the NA segment sequences, the phylogeny of the other segment sequences, with the exception of the NS segment, showed distinct grouping patterns based on geographic origin rather than formal subtype assignment. Reassortment events leading to complex phylogenetic relationships were frequently observed. In addition, multiple cases of previously undescribed reassortments between subtypes were detected, emphasizing the fluidity of H7Nx virus populations. These results indicate a high degree of genetic diversity and reassortment within H7Nx influenza viruses. In other words, H7Nx viruses exist as constantly changing combinations of gene pools rather than stable genetic lineages. Full article

Avian influenza (AI) is an extremely contagious viral disease of domestic and wild birds that can spread rapidly among bird populations, inducing serious economic losses in the poultry industry. During the winter season 2021–2022, we isolated seventeen highly pathogenic avian influenza (HPAI) H5N8 viruses from outbreaks involving ducks in Egypt, occurring in both backyard and farm settings. The aim of this study was to pinpoint genetic key substitutions (KSs) that could heighten the risk of a human pandemic by influencing the virus’s virulence, replication ability, host specificity, susceptibility to drugs, or transmissibility. To understand their evolution, origin, and potential risks for a human pandemic, whole-genome sequencing and phylogenetic analysis were conducted. Our analysis identified numerous distinctive mutations in the Egyptian H5N8 viruses, suggesting potential enhancements in virulence, resistance to antiviral drugs, and facilitation of transmission in mammals. In this study, at least five genotypes within one genome constellation of H5N8 viruses were identified, raising concerns about the potential emergence of novel viruses with altered characteristics through reassortment between different genotypes and distinct groups. These findings underscore the role of ducks in the virus’s evolutionary process and emphasize the urgent need for enhanced biosecurity measures in domestic duck farms to mitigate pandemic risk. Full article

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

Porcine rotavirus (PoRV) is a significant enteric pathogen causing gastroenteritis in piglets, which causes huge economic loss to the Chinese pig industry. In this study, six porcine rotavirus A strains were isolated from three adjacent sow farms belonging to the same company within one year, which suffered severe diarrhea outbreaks. AHBZ2303 (G11P[7]) and AHBZ2305 (G9P[23]), AHBZ2304 (G9P[23]) and AHBZ2312 (G4P[6]), AHBZ2310 (G9P[23]) and AHBZ2402 (G5P[23]) were isolated from Farm A, B and C, respectively. All six isolates were related to human rotavirus through complete genome analysis, suggesting the potential cross–species infection between humans and pigs. Evolutionary analysis revealed that AHBZ2303 and AHBZ2304 likely emerged simultaneously in Farm A and B, and then AHBZ2304 was introduced to Farm A and C, leading to the emergence of AHBZ2305 and AHBZ2310. Recombination and large variation were identified for AHBZ2312 and AHBZ2402. These findings provided insights into the transmission and evolution of PoRV among farms and underscored the need for enhanced monitoring to mitigate the risk of outbreaks from novel variants. Full article