Search Results (170)

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that circulates primarily within animal populations and occasionally spills over to humans, causing severe neurological disease. While humans are terminal hosts, veterinary species such as pigs and birds play essential roles in viral amplification and maintenance, making JEV fundamentally a veterinary infectious disease with zoonotic potential. This review summarizes the current understanding of JEV transmission dynamics from a veterinary and ecological perspective, emphasizing the roles of amplifying hosts and animal surveillance in controlling viral circulation. Recent genotype shifts and viral evolution have raised concerns regarding vaccine effectiveness and regional emergence. National surveillance systems and animal-based monitoring strategies are examined for their predictive value in detecting outbreaks early. Veterinary and human vaccination strategies are also reviewed, highlighting the importance of integrated One Health approaches. Advances in modeling and climate-responsive surveillance further underscore the dynamic and evolving landscape of JEV transmission. By managing the infection in animal reservoirs, veterinary interventions form the foundation of sustainable zoonotic disease control. Full article

GW4869, a cell-permeable, selective inhibitor of neutral sphingomyelinase is a pharmacological agent that blocks the production and release of extracellular vesicles (EVs). Our previous studies have shown that GW4869 inhibits flaviviral loads in tick, mosquito and mammalian cells, including murine cortical neurons. Yet the mechanism(s) of GW4869 inhibitor upon viral infections were not addressed. In the current study, we focused on how GW4869 interferes with Langat Virus (LGTV, a tick-borne flavivirus) replication in ISE6 tick cells. First, we found that GW4869 is neither cytotoxic at tested doses of 50, 100, and 150 µM in tick cells, nor does it directly bind to the free LGTV present in cell culture supernatants. When tick cells were treated with GW4869, followed by infection with viral stock at dilutions of 10⁻², 10⁻³, 10⁻⁴ (the infectious dose determination by viral dilution assay), it affected LGTV replication in tick cells. A reduction in viral burden was noted in GW4869-treated tick cells, which constituted more than half the amount of decrease when compared to the mock control. Next, GW4869 treatment not only resulted in decreased LGTV transcript levels in tick cells and EVs derived from these infected cells, but also revealed diminished EVs concentrations. Enhanced IsSMase transcripts in the LGTV-infected group was noted upon GW4869 treatment, thus suggesting a host response to perhaps inhibit virus replication. In addition, GW4869 treatment reduced LGTV loads in density gradient EVs fractions, which correlated with decreased EVs concentration in those fractions. These data not only indicate that GW4869 affects LGTV replication, but that it also interferes with EV secretion and release from tick cells. Lastly, we found that GW4869 inhibits LGTV replication in tick cells but does not directly affect the infectivity of LGTV viral particles. Overall, our study suggests that GW4869 is a potential therapeutic inhibitor in controlling tick-borne diseases. Full article

Neuroinvasive arboviruses such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Usutu virus (USUV), and Toscana virus (TOSV) have (re-)emerged with increasing incidence and geographic range. We analyzed the epidemiology of arboviral infections in Croatia during the 2024 transmission season. A total of 154 patients with neuroinvasive diseases (NID), 1596 horses, 69 dead birds, and 7726 mosquitoes were tested. Viral RNA was detected using RT-qPCR. IgM/IgG-specific antibodies were detected using commercial ELISA or IFA, with confirmation of cross-reactive samples by virus neutralization test. RT-qPCR-positive samples were Sanger sequenced. Arboviral etiology was confirmed in 33/21.42% of patients with NID. WNV was most frequently detected (17/11.03%), followed by TBEV (10/6.49%), USUV (5/3.24%), and TOSV (1/0.64%). WNV infections were reported in regions previously known as endemic, while in one continental county, WNV was recorded for the first time. USUV infections re-emerged after a six-year absence. In addition to human cases, acute WNV infections were recorded in 11/395 (2.78%) of horses and two dead crows. WNV IgG seropositivity was detected in 276/1168 (23.63%) and TBEV IgG seropositivity in 68/428 (15.88%) horses. None of the tested mosquito pools were positive for WNV and USUV RNA. Phylogenetic analysis showed the circulation of WNV lineage 2 and Usutu Europe 2 lineage. Climate conditions in 2024 in Croatia were classified as extremely warm, which could, at least in part, impact the quite intense arboviral season. The spreading of flaviviruses in Croatia highlights the need for continuous surveillance in humans, animals, and vectors (“One Health”). Full article

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare JEV genotypes poses additional risks. In this study, a phylogenetic analysis of the whole JEV genome sequence, along with a temporal–spatial analysis of isolates and a host–vector analysis, was used to examine the changes in JEV transmission dynamics before and after 2012. The results revealed persistent differences between the dominant G1 and G3 genotypes, as well as the re-emergence of G4 and G5 genotypes. Although JEV has been detected in non-traditional vectors and atypical mammalian hosts, Culex tritaeniorhynchus and pigs remain the primary vector and amplifying host, respectively. These findings underscore the need to enhance existing JEV genotype surveillance while addressing emerging threats from genotype diversity, host expansion, and geographic spread. Full article

Flaviviruses are usually transmitted to humans via mosquito or tick bites, whose infections may lead to severe diseases and fatality. During intracellular infection, they remodel the endoplasmic reticulum (ER) membrane to generate compartments scaffolding the replication complex (RC) where replication of the viral genome takes place. In this study, we purified the ER membrane fraction of virus infected cells to identify the proteins that were enriched during flavivirus infection. We found that tripartite motif-containing proteins (TRIMs) including TRIM38, TRIM21, and TRIM14 were significantly enriched during infection with mosquito-borne (West Nile virus strain Kunjin and Zika virus (ZIKV)) and tick-borne (Langat virus (LGTV)) flaviviruses. Further characterizations showed that TRIM21 and TRIM14 act as restriction factors against ZIKV and LGTV, while TRIM38 hinders ZIKV infection. These TRIMs worked as interferon-stimulated genes to mediate IFN-I response against LGTV and ZIKV infections. Restriction of ZIKV by TRIM14 and TRIM38 coincides with their colocalization with ZIKV NS3. TRIM14-mediated LGTV restriction coincides with its colocalization with LGTV NS3 and NS5 proteins. However, TRIM21 did not colocalize with ZIKV and LGTV NS3 or NS5 protein suggesting its antiviral activity is not dependent on direct targeting the viral enzyme. Finally, we demonstrated that overexpression of TRIM21 and TRIM14 restricted LGTV replication. Full article

Yellow fever (YF) causes severe morbidity and mortality in Africa and South America. It is an arthropod-borne viral disease endemic to tropical regions of Africa and South America. Yellow fever virus (YFV) is transmitted by mosquitoes and frequently affects both non-human primates (NHPs) and humans. Neotropical primates (NTPs) are generally more severely afflicted by YFV than African primates. Asian primates appear not to be susceptible to this disease. Susceptibility varies among NTP species: asymptomatic infections are described in some NTP species, whereas severe epizootic mortality events are described in others. The genus Alouatta (howler monkeys) is considered to be the most susceptible among the NTPs. Epizootic events resulting in the death of thousands of NTPs have been recorded in recent history. As a result, YFV poses a threat to the survival of some NTP species. In most cases, NTPs are found dead without showing prior clinical signs. In cases where clinical signs are observed, they are mostly non-specific. Due to their high susceptibility, epizootic events in NTPs are used as epidemiological predictors for human YF outbreaks. YFV infection may be diagnosed by means of virus isolation, reverse transcription polymerase chain reaction, serology, histopathology, or immunohistochemistry. Animals that survive the disease develop neutralizing antibodies to YFV. Currently, no specific treatment is available. Sustained YF control strategies must rely on surveillance and accurate diagnostics to allow for early detection of outbreaks and rapid implementation of control measures. Prophylaxis should be based on a One Health perspective that recognizes the intricate interplay between human health, primate health, and the environment. Vaccines for YF are available, with the human 17DD vaccine effectively preventing disease in primates. However, mitigation strategies continue to rely more and more on vector control, preferably using eco-friendly methods. Climate change and human activities, and their impact on local ecology, are assumed to increase the risk of YF transmission in the next decades. Full article

West Nile Virus (WNV), a mosquito-borne pathogen, is a growing public health challenge across Europe. Environmental and anthropogenic factors have led to the spread of the virus to higher geographic latitudes, as well as to increased viral circulation and genetic diversity. Aims: This study aimed to describe the epidemiological, clinical, and laboratory characteristics of WNV cases in Bulgaria during 2024 and to investigate WNV phylogenetics. Epidemiological, clinical and laboratory data from 32 patients with confirmed or probable WNV infections were collected and analysed. Complete viral genomes were obtained from two samples using whole genome sequencing (WGS). Phylogenetic analysis was performed using the Nextstrain WNV analysis pipeline. Severe disease was observed in 21 patients, with three fatalities reported in older males with comorbidities. Phylogenetic analysis revealed that Bulgarian strains clustered within the Central/Southern European clade of lineage 2, closely related to Greek strains. Evidence suggested localised viral evolution following cross-border introduction from Greece. Our study provides a detailed clinical and laboratory characterization of the human WNV cases detected in Bulgaria in 2024. Improved diagnostic workflows, expanded laboratory resources and increased molecular surveillance are essential to better understand the burden of WNV infections in Bulgaria, as well as to follow the evolution and spread of the virus. Full article

Following its initial documented emergence in Hunan’s swine facilities in 2017, GETV has inflicted considerable financial damage upon China’s pork production sector. Beyond its impact on swine, GETV also poses a potential risk to other animal species and public health, primarily due to its mosquito-borne transmission. Between September 2020 and May 2021, a GETV outbreak occurred on a commercial swine farm in Sichuan Province, where affected animals exhibited movement disorders, neurological symptoms, and mild diarrhea, with severe cases resulting in mortality. To elucidate the genetic characteristics and transmission dynamics of the virus, a comprehensive investigation of this outbreak was conducted. Clinical samples from diseased or deceased swine were collected and analyzed by PCR, confirming the presence of GETV infection. Additionally, differential diagnostic assays were performed for other common swine pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PRV), classical swine fever virus (CSFV), and atypical porcine pestivirus (APPV). All tests yielded negative results, confirming GETV as the sole etiological agent of the outbreak. The GETV-positive samples were inoculated into BHK-21 cells, leading to the isolation of a GETV strain (SC202009). Whole-genome sequence analysis revealed that SC202009 belongs to the GIII genotype of GETV, with a nucleotide sequence identity ranging from 95.1% to 99.8% compared to reference sequences in GenBank. This high level of sequence identity suggests that SC202009 is closely related to other circulating strains in the region, indicating potential local transmission networks and endemic viral circulation. The nucleotide sequence identity of the E2 gene ranged from 94.2% to 99.6%, while the E2 protein amino acid sequence identity ranged from 97.2% to 99.5%. Phylogenetic analysis further indicated that SC202009 is genetically distant from the original Malaysian prototype strain (MM2021) but shares high sequence identity with several strains isolated in Sichuan Province, including SC266, SC201807, and SC483. Notably, NMJA_F2_18-8L-NH-Cxp-Y-1-1 was isolated from Culex pipiens, suggesting a mosquito-borne transmission route. These findings provide novel insights into the regional dissemination patterns and genetic diversity of GETV in China. These results also highlight the importance of the continuous surveillance of viral genetic variations and the elucidation of transmission dynamics to develop effective control strategies and mitigate potential public health risks. Future studies should focus on the ecological and environmental factors influencing GETV transmission, particularly the role of mosquito vectors in cross-species viral spread, to enhance targeted prevention and control measures for this emerging arboviral threat. Full article

Orthoflavivirus, a genus encompassing arthropod-borne, positive-sense, single-stranded RNA viruses in the Flaviviridae family, represents clinically relevant viruses that pose significant threats to human and animal health worldwide. With warming climates and persistent urbanization, arthropod vectors and the viruses they transmit continue to widen their geographic distribution, expanding endemic zones. Flaviviruses such as dengue virus, Zika virus, West Nile virus, and tick-borne encephalitis virus cause debilitating and fatal infections globally. In 2024, the World Health Organization and the Pan American Health Organization declared the current dengue situation a Multi-Country Grade 3 Outbreak, the highest level. FDA-approved treatment options for diseases caused by flaviviruses are limited or non-existent, and vaccines are suboptimal for many flaviviruses. Understanding the molecular characteristics of the flavivirus life cycle, virus-host interactions, and resulting pathogenesis in various cells and model systems is critical for developing effective therapeutic intervention strategies. This review will focus on the virus-host interactions of mosquito- and tick-borne flaviviruses from the virus replication and assembly perspective, emphasizing the interplay between viral non-structural proteins and host pathways that are hijacked for their advantage. Highlighting interaction pathways, including innate immunity, intracellular movement, and membrane modification, emphasizes the need for rigorous and targeted antiviral research and development against these re-emerging viruses. Full article

Dengue fever is a widespread mosquito-borne viral disease caused by infections with dengue virus (DENV). Since its initial detection in 1979, the disease has posed a significant public health threat to the Lao People’s Democratic Republic (Lao PDR). Surveillance is crucial for understanding the circulation of DENV in endemic regions and identifying potential hot spots with higher-than-expected case numbers of dengue fever. In this study, we present the results from our surveillance activities in the Lao PDR spanning 2020–2023. While quarantine restrictions from the COVID-19 pandemic posed substantial disruptions to performing DENV surveillance, over 8800 samples were tested during this period, with a positive rate of close to 60%. Cases were reported from all three regions (northern, Central, and southern) of the Lao PDR. Three circulating serotypes (DENV-1, DENV-2, and DENV-4) were detected, with DENV-1 dominant in 2021 and 2022, while DENV-2 was dominant in 2020 and 2023. Phylogenetic analyses suggest that the genotypes of DENV-1, DENV-2, and DENV-4 were closely related to corresponding isolates from neighboring countries. These findings provide an update on the nature of DENV cases detected in the Lao PDR and underscore the critical importance of sustaining a robust surveillance network to track infections. Full article

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual compound screening. We have identified three inhibitors that have potent activities against Dengue, West Nile, and Zika viruses. All these three inhibitors are Benzothiophene derivatives. This is the first report of Benzothiophene-derived compounds as inhibitors for flaviviruses. Furthermore, our approach has provided a proof-of-concept that it is feasible to identify shared drugs for several different viral species of flaviviruses. Full article

Rift Valley fever (RVF) is a devastating zoonotic mosquito-borne viral hemorrhagic fever disease that threats human and animal health and biodiversity in Africa, including in Rwanda. RVF is increasingly outbreaking in Africa, leading to devastating impacts on health, socioeconomic stability and growth, and food insecurity in the region, particularly among livestock-dependent communi-ties. This systematic review synthesizes existing evidence on RVF’s epidemiology, transmission dynamics, and the prevention and control measures implemented in Rwanda. Our findings high-light the rapidly increasing prevalence of RVF and the expansion of its geographical distribution and host range in Rwanda. Furthermore, the review reveals gaps in local evidence, including the existence of competent vectors of RVFV and the risk factors associated with the emergence and spread of RVF in the country. This underscores the urgent need for prospective research to inform evidence-based health policymaking, strategic planning, and the development and implementation of cost-effective preventive and control measures, including diagnosis and surveillance for early detection and response. It also calls for the institutionalization of a cost-effective, multisectoral, and transdisciplinary One Health strategy for reducing the burden and risk of climate climate-sensitive and zoonotic diseases, including RVF, in the country. We recommend exploring cost-effective human and/or animal vaccination mechanisms for RVF, integrating AI-powered drones into dis-ease vectors surveillance and control, and the routine implementation of genomics-enhanced xenosurveillance to monitor changes in pathogens and vectors dynamics in order to inform poli-cymaking and guide the control interventions. Full article

Dengue fever, caused by the dengue virus (DENV), poses a significant global health challenge, particularly in tropical and subtropical regions. Recent increases in indigenous DENV cases in Europe are concerning, reflecting rising incidence linked to climate change and the spread of Aedes albopictus mosquitoes. These vectors thrive under environmental conditions like temperature and humidity, which are increasingly influenced by climate change. Additionally, global travel accelerates the cross-border spread of mosquito-borne diseases. DENV manifests clinically in a spectrum from asymptomatic cases to severe conditions like dengue hemorrhagic fever and dengue shock syndrome, influenced by viral serotype and host factors. In 2024, Brazil experienced a fourfold increase in dengue cases compared to 2023, accompanied by higher mortality. Conventional control measures, such as vector control, community engagement, and vaccination, proved insufficient as climate change exacerbated mosquito proliferation, challenging containment efforts. In this regard, our review analyzes prevention measures and therapeutic protocols during the outbreak while addressing DENV transmission dynamics, clinical presentations, and epidemiological shifts. It also evaluates diagnostic strategies combining clinical assessment with serological and molecular testing, providing information to improve diagnostic and preventive measures. The global expansion of dengue-endemic regions, including outbreaks in Europe, highlights the urgent need for enhanced surveillance, proactive interventions, and international collaboration to mitigate the growing threat of Dengue and other arboviruses like West Nile, Zika, Chikungunya, Oropouche, and Yellow Fever viruses. Full article

Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKV^MR-766, rJEV/ZIKV^P6-740, and rJEV/ZIKV^PRVABC-59), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA₁₄-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKV^P6-740 exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKV^MR-766 and rJEV/ZIKV^PRVABC-59, as well as their vector, rJEV. In IFNAR^−/− mice, an animal model of ZIKV infection, subcutaneous inoculation of rJEV/ZIKV^P6-740 caused a low-level localized infection limited to the spleen, with no clinical signs of infection, weight loss, or mortality; in contrast, the other two chimeric viruses and their vector caused high-level systemic infections involving multiple organs, consistently leading to clear clinical signs of infection, rapid weight loss, and 100% mortality. Subsequently, subcutaneous immunization with rJEV/ZIKV^P6-740 proved highly effective, offering complete protection against a lethal intramuscular ZIKV challenge 28 days after a single-dose immunization. This protection was specific to ZIKV prM/E and likely mediated by neutralizing antibodies targeting ZIKV prM/E. Therefore, our data indicate that the chimeric virus rJEV/ZIKV^P6-740 is a highly promising vaccine prototype for developing a safe and effective vaccine for inducing neutralizing antibody-mediated protective immunity against ZIKV. Full article

Japanese Encephalitis (JE) is the leading cause of viral encephalitis in regions with endemic Japanese Encephalitis Virus (JEV) infections. Background/Objectives: The aim of this review is to consider the potential role of artificial intelligence (AI) to improve detection, monitoring and public health interventions for JE. Discussion: As climate change continues to impact mosquito population growth patterns, more regions will be affected by mosquito-borne diseases, including JE. Improving diagnosis and surveillance, while continuing preventive measures, such as widespread vaccination campaigns in endemic regions, will be essential to reduce morbidity and mortality associated with JEV. Conclusions: With careful integration, AI mathematical and mechanistic models could be useful tools for combating the growing threat of JEV infections globally. Full article