Search Results (379)

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Dengue virus (DENV) poses a major global health concern, with over 6.5 million cases and 7300 deaths reported in 2023. Accurate serological assays are essential for tracking infection history, evaluating disease severity, and guiding vaccination strategies. However, existing assays are limited in their specificity, sensitivity, and cross-reactivity. Using optical modulation biosensing (OMB) technology and non-structural protein 1 (NS1) antigens from DENV-1–3, we developed highly sensitive and quantitative serotype-specific anti-DENV NS1 IgG serological assays. The OMB-based assays offered a wide dynamic range (~4-log), low detection limits (~400 ng/L), fast turnaround (1.5 h), and a simplified workflow. Using samples from endemic (Vietnam) and non-endemic (Israel) regions, we assessed intra-DENV and inter-Flavivirus cross-reactivity. Each assay detected DENV infection with a 100% sensitivity for the corresponding serotype and 64% to 90% for other serotypes. Cross-reactivity with Zika, Japanese encephalitis, and West Nile viruses ranged from 21% to 65%, reflecting NS1 antigen conservation. Our study provides valuable insights into the cross-reactivity of DENV NS1 antigens widely used in research and highlights the potential of OMB-based assays for quantitative and epidemiological studies. Ongoing efforts should aim to minimize cross-reactivity while maintaining sensitivity and explore integration with complementary platforms for improved diagnostic precision. Full article

Orthoflaviviruses (formerly flaviviruses) are known for their role in numerous diseases affecting both humans and animals. Despite the worldwide distribution of orthoflaviviruses, individual species are only found in endemic or epidemic regions. However, in recent decades, certain orthoflaviviruses have spread beyond their traditional geographic boundaries, even crossing continents. Given the long-distance movements of birds, the knowledge of zoonotic orthoflaviviruses associated with birds is essential because of their possible introduction into new regions, as was the case with West Nile virus and Usutu virus. A thorough literature review was conducted on zoonotic orthoflaviviruses related to birds, including lesser-known (re-)emerging and neglected orthoflaviviruses that are limited to specific regions and/or avian hosts but have the potential to spread to a wider geographical area and pose a higher risk of transmission to humans. Several of these viruses possess significant zoonotic potential and can cause a wide spectrum of diseases in humans, ranging from mild febrile illnesses (Zika virus) to severe neuroinvasive diseases (tick-borne encephalitis, West Nile, Japanese encephalitis virus) and hemorrhagic fevers (yellow fever, dengue virus). Geographic distribution, hosts, vectors, incidence of human infections, and impact on human and animal health of zoonotic flaviviruses related to birds are critically reviewed. The viruses have been categorized based on the role of birds as an orthoflavivirus host and the clinical presentation in human infections. Full article

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

Mosquitoes of the Aedes and Culex genera are primary vectors of arboviruses such as the dengue, Zika, chikungunya (CHIKV), Oropouche, and West Nile viruses, causing millions of infections annually. Standard virus detection in mosquitoes requires capturing, transporting, and processing samples with a cold chain to preserve RNA, which is challenging in resource-limited areas. FTA cards preserve viral RNA at room temperature and have been used to collect mosquito saliva, a key sample for assessing transmission. However, most FTA-based traps require electricity or CO₂, limiting use in low-resource settings. This study adapted and evaluated the BR-ArboTrap, a low-cost trap derived from an oviposition trap, integrating a sugar-based attractant with FTA cards to collect mosquito saliva, without electricity or refrigeration. Aedes aegypti exposed to CHIKV were used in three experiments to evaluate: (i) RNA preservation under different conditions, (ii) the minimum number of positive mosquitoes for detection, and (iii) RNA amounts on FTA versus blood. RT-qPCR detected CHIKV RNA in 90% of FTA cards and 96% of exposed mosquitoes. RNA remained stable under varying conditions, with no significant difference compared to blood. BR-ArboTrap is an effective, affordable, and field-ready tool to enhance arbovirus surveillance in remote and low-resource areas. 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

West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood–brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration. Full article

Though a variety of methods are used to conduct West Nile virus (WNV) surveillance, accurate prediction and prevention of outbreaks remain a global challenge. Previous studies have established that the concentration of antibodies to mosquito saliva is directly related to the intensity of exposure to mosquito bites and can be a good proxy to determine risk of infection in human populations. To assess exposure characteristics and transmission dynamics among avian communities, we tested the levels of IgY antibodies against whole salivary glands of Aedes albopictus and Culex quinquefasciatus, as well as WNV antigen, in 300 Northern cardinals sampled from April 2019 to October 2019 in St. Tammany Parish, Louisiana. Though there were no significant differences in antibody responses among sex or age groups, exposure to Ae. albopictus bites was more positively associated with exposure to WNV compared with Cx. quinquefasciatus exposure (ρ = 0.2525, p < 0.001; ρ = 0.1752, p = 0.02437). This association was more pronounced among female birds (ρ = 0.3004, p = 0.0075), while no significant relationship existed between exposure to either mosquito vector and WNV among male birds in the study. In general, two seasonal trends in exposure were found, noting that exposure to Ae. albopictus becomes less intense throughout the season (ρ = −0.1529, p = 0.04984), while recaptured birds in the study were found to have increased exposure to Cx. quinquefasciatus by the end of the season (ρ = 0.277, p = 0.0468). Additionally, we report the identification of several immunogenic salivary proteins, including D7 family proteins, from both mosquito vectors among the birds. Our results suggest that Ae. albopictus may have a role in early-season transmission of WNV, particularly among brooding females and hatchling cardinals. However, bloodmeal analysis was not included in this work and further studies are needed to verify this assumption. Yet, broad circulation of WNV in nesting avian communities could enhance risk of infection among Cx. quinquefasciatus mosquitoes in the late season, with the potential to contribute to human disease incidence and epizootic spillover in the environment. Full article

Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic outbreaks and significant economic burdens due to hospitalizations and treatments. They share antigens, leading to cross-reactivity where antibodies generated against one flavivirus can react with others, complicating the accurate diagnosis of individual infections and making the development of treatments or vaccines more challenging. The role of T cells in the immune response to flaviviruses is a complex topic debated by scientists. On one hand, T cells help control infection by eliminating infected cells and protecting against disease. However, there is evidence that an excessive or dysregulated T cell response can cause tissue damage and worsen the disease, as seen in severe dengue cases. This duality underscores the complexity of the immune response to flavivirus infections, posing a significant challenge for researchers. Gaining a deeper understanding of the immune response at the cellular level, particularly the role of T follicular helper cells, can reveal new avenues of investigation that could lead to novel strategies for disease management. This review explores the dynamics of T cell responses, focusing on circulatory T follicular helper cells (cT_FH), to enhance our understanding of flavivirus immunity and inform future interventions. 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

Avian influenza (AI), caused by Alphainfluenzavirus (family Orthomyxoviridae), poses significant threats to poultry, biodiversity, and public health. AI outbreaks in poultry lead to severe economic losses, while highly pathogenic strains (HPAIVs) severely impact wild bird populations, with implications for biodiversity and potential zoonotic risks. Similarly, arboviruses such as West Nile virus (WNV) and Usutu virus (USUV) are emerging zoonoses. WNV can cause severe neurological diseases in birds, humans, and other animals, while USUV significantly affects blackbird populations and has zoonotic potential, though human cases remain rare. This study investigated avian viruses in 1654 wild birds from 75 species that died at the Wildlife Rescue Center in Vanzago, Lombardy, during 2023–2024. Necropsies were conducted, and virological analyses were performed to detect avian influenza viruses, WNV, and USUV. Among the tested birds, 15 were positive for H5N1 HPAIV clade 2.3.4.4b, all in 2023, including 13 Chroicocephalus ridibundus, one Coturnix coturnix, and one Columba palumbus. Additionally, 16 tested positive for WNV (15 for lineage 2 and one for lineage 1), one for USUV, and 11 co-infections WNV/USUV were recorded in 2023–2024. These findings underscore the importance of avian viral passive surveillance in identifying epidemiological trends and preventing transmission to other species, including mammals and humans. Full article

We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico, in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by the plaque reduction neutralization test (PRNT) for antibodies to eight orthoflaviviruses (dengue viruses 1–4, St. Louis encephalitis virus, T’Ho virus, West Nile virus, and Zika virus) and one alphavirus (chikungunya virus; CHIKV). Twelve (12.8%) bats and 15 (34.9%) opossums contained orthoflavivirus-specific antibodies. One bat (a Jamaican fruit bat) was seropositive for Zika virus, and 11 bats contained antibodies to an undetermined orthoflavivirus, as did the 15 opossums. All bats and most opossums seropositive for an undetermined orthoflavivirus had low PRNT titers, possibly because they had been infected with another (perhaps unrecognized) orthoflavivirus not included in the PRNTs. Antibodies that neutralized CHIKV were detected in three (7.0%) opossums and none of the bats. The three opossums had low CHIKV PRNT titers, and therefore, another alphavirus may have been responsible for the infections. In summary, we report serologic evidence of arbovirus infections in bats and opossums in Chiapas, Mexico. Full article

Mosquito-borne diseases such as dengue and West Nile virus pose serious public health risks. On Madeira Island, the presence of the mosquito species Aedes aegypti (Linnaeus, 1762) and Culex pipiens (Linnaeus, 1758) raises concerns about local transmission. In this study, we tested 100 Ae. aegypti and 40 Cx. pipiens mosquitoes collected exclusively in the municipality of Funchal, Madeira Island, to assess the presence and diversity of Wolbachia, a naturally occurring bacterium known to reduce mosquitos’ ability to transmit viruses. Molecular identification confirmed that all Cx. pipiens specimens belonged to the molestus biotype, with three individuals identified as hybrids between molestus and pipiens biotypes. This is the first evidence of such hybrids in Madeira. Wolbachia was not detected in any of the Ae. aegypti samples. In contrast, all Cx. pipiens mosquitoes were positive, showing a 100% prevalence. Genetic characterization placed these infections within the wPip clade, supergroup B, sequence type 9. These findings provide key baseline data to inform future mosquito control strategies on the island. As Ae. aegypti showed no natural Wolbachia infection, introducing Wolbachia-infected mosquitoes may be necessary to implement such biocontrol approaches in Madeira. Full article

The 1999 outbreak of West Nile virus (WNV) in New York City (NYC) marked the first documented introduction of the virus into the western hemisphere, prompting extensive public health surveillance. This study examines the epidemiology of WNV from 2000 to 2019, analyzing 381 human cases, including 66 cases of West Nile Fever (WNF) and 315 cases of West Nile Neuroinvasive Disease (WNND), with 35 fatalities. Simultaneously, 6632 WNV-positive mosquito pools were identified across 16 species. While Culex pipiens and Cx. restuans accounted for 91.4% of positive pools, Cx. salinarius, which comprised only 6.2%, exhibited a stronger correlation with human infections. Human surveillance involved comprehensive case investigations following laboratory-confirmed WNV infections, incorporating structured interviews with patients and healthcare providers. Mosquito surveillance was conducted through weekly collections from 52–71 permanent trap sites, supplemented by approximately 200 additional sites annually in areas with elevated WNV activity. Captured mosquitoes were species-identified, pooled, and tested for WNV RNA via RT-PCR. Findings highlight the dominant role of Culex species, particularly Cx. salinarius, in human WNV transmission, with 69% of cases occurring near WNV-positive mosquito pools. Spatial analyses identified transmission hotspots, emphasizing the importance of species-specific mosquito control strategies. Over the study period, WNV activity has increased in NYC, likely influenced by climate change, as warmer summers and extended breeding seasons align with peak outbreaks. Integrating spatial mapping, climate forecasting, and targeted surveillance could significantly improve WNV mitigation efforts in urban environments. 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