Search Results (855)

Orthoflavivirus encephalitidis (tick-borne encephalitis virus, TBEV) is of high concern due to its ability to cause severe neurological manifestations. Despite the fact that the role of NS1 proteins from various mosquito-borne flaviviruses in pathogenesis and their ability to affect human endothelial permeability have been investigated, TBEV NS1 has thus far been insufficiently studied. In this study, human endothelial permeability was assessed using TEER and transwell permeability assays. Signaling pathways were determined by RNAseq. The ability of the NS1 protein of TBEV to affect human endothelial permeability was investigated for the first time. It was shown that recombinant TBEV NS1 produced in eucaryotic cells directly affected human lung microvascular endothelial cells (HLMVECs) in vitro but not human umbilical vein endothelial cells (HUVECs). It was indicated that TBEV NS1 induced endothelial hyperpermeability of HLMVECs through activating TNF-α and other inflammatory signaling pathways. Full article

Arboviruses transmitted by Aedes aegypti pose a significant challenge in Ecuador, as they are persistent, emerging, and re-emerging. During the SARS-CoV-2 pandemic, these diseases were temporarily overshadowed. This study aimed to detect and identify arbovirus species in mosquitoes collected from two communities in Manabí province—Caja Fuego (rural) and San Gregorio (marginal urban). A total of 468 mosquitoes were collected—385 from Caja Fuego and 83 from San Gregorio—and grouped into 72 pools. Samples were transported to CISeAL under proper biosafety protocols, homogenized, and analyzed using End-Point PCR, RT-PCR, and Sanger sequencing. The results revealed the presence of Flaviviruses and Alphaviruses. Of the 22 Flavivirus pools tested, 18 were positive, with PCR analysis specifically identifying dengue and Zika. Although no arbovirus was identified via RT-PCR, Sanger sequencing detected two Zika-positive samples. Notably, no official Zika cases were reported in 2023, suggesting a potential undetected risk of infection in human populations of Caja Fuego and San Gregorio. This study recommends the implementation of a surveillance campaign in collaboration with the Ecuadorian Ministry of Public Health to mitigate the risk. Full article

Background/Objective: Yellow fever (YF) is an acute infectious disease caused by the yellow fever virus which is transmitted by mosquitoes. Neotropical primates are susceptible to infection, which is often presented as epizootic outbreaks. The aim was to evaluate and characterize the immune response against YF in different species of neotropical primates from the Belo Horizonte Zoo. Methods: Vaccine 17DD was administered to 24 neotropical primates, with a single subcutaneous dose. Clinical exams, RNAemia, and detection of IgG and neutralizing antibodies against YFV were performed. In addition, an ethogram was performed to assess clinical changes and animal welfare. Results: At 4 days post-vaccination, RNAemia was detected in nine animals. There was seroconversion and persistence of immune response in Alouatta guariba clamitans, Sapajus xanthosternos, Saguinus imperator and Aotus infulatus. However, the vaccine was not immunogenic for Lagothrix cana. In Pithecia irrorata seroconversion did not persist long term, while the Ateles sp. had a transient immune response. No significant clinical manifestations were observed in any of the vaccinated animals. Conclusions: This study demonstrated a safe, immunogenic and persistent immune response induced by the attenuated 17DD vaccine strain in A. guariba clamitans, S. xanthosternos, S. imperator, and A. infulatus. 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

The Zika virus (ZIKV) gained prominence as a significant global pathogen after the 2015–2016 outbreaks associated it with an increase in neurological complications in adults and congenital malformations. Different mechanisms have been proposed by which ZIKV may cross the blood–brain barrier and reach the central nervous system to cause neuroinflammation. Although ZIKV infection triggers a robust immune response, the virus has developed different strategies to escape it. Furthermore, although the virus is present in areas with cocirculation of other pathogenic agents, few studies have evaluated the cross-immune reactions and coinfection of ZIKV. Coinfections of ZIKV with other viruses, parasites, and bacteria are described. Such interactions can worsen infections and alter the immune response, imposing new therapeutic challenges and highlighting the need for more studies in the field. In this review, we discuss various aspects of ZIKV biology, focusing on the impacts of coinfections. Full article

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), which help indicate host immunity after vaccination. Current vaccines primarily focus on neutralizing antibodies (nAbs) against the viral envelope E protein, though emerging evidence suggests other potential targets may also be effective in disease prevention. Additionally, there is growing evidence of cross-protection between different flaviviruses when immunity to one virus is achieved, although this can be limited by antibody-dependent enhancement. This review examines the current understanding of flavivirus immunity, CoPs, and the potential for cross-protection in the context of existing vaccine strategies. 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

Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, there is still a huge demand for new diagnostic methods that provide rapid, low-cost, easy-to-use confirmation. Thus, in this study, we developed an affordable electrochemical biosensor for rapidly detecting immunoglobulin G (IgG) serological antibodies in the sera of DENV-infected patients. An identified linear B-cell epitope (DENV/18) specific for DENV 1–4 serotypes recognized by IgG in patient sera was selected as a target molecule after a microarray of peptides using the SPOT-synthesis methodology. After chemical synthesis, the DENV/18-peptide was immobilized on the surface of the working electrode of a commercially available screen-printed gold electrode (SPGE). The capture of DENV-specific IgG allowed for the formation of an immunocomplex that was measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using a potassium ferrocyanide/ferricyanide ([Fe(CN)₆]^3−/4−) electrochemical probe. An evaluation of the biosensor’s performance showed a detection limit of 100 µg mL⁻¹ for the synthetic peptides (DENV/18) and 1.21 ng mL⁻¹ in CV and 0.43 ng mL⁻¹ in DPV for human serum, with a sensitivity of 7.21 µA in CV and 8.79 µA in DPV. The differentiation of infected and uninfected individuals was possible even at a high dilution factor that reduced the required sample volumes to a few microliters. The final device proved suitable for diagnosing DENV by analyzing real serum samples, and the results showed good agreement with molecular biology diagnostics. The flexibility to conjugate other antigenic peptides to SPEs suggests that this technology could be rapidly adapted to diagnose other pathogens. Full article

Insect-borne viruses may account for a significant proportion of non-malaria and non-bacterial febrile illnesses in Liberia. Although the presence of many arthropod vectors has been documented, the collective burden of arbovirus infections and baseline pre-existing immunity remains enigmatic. Our goal was to determine the seroprevalence of arbovirus exposure across the country using a resource-sparing, multiplex immunoassay to determine IgG responses to immunodominant antigens. 532 human serum samples, from healthy adults, collected from 10 counties across Liberia, were measured for IgG reactivity against antigens of eight common flavi-, alpha-, and orthobunya/nairoviruses suspected to be present in West Africa. Approximately 32.5% of our samples were reactive to alphavirus (CHIKV) E2, ~7% were reactive separately to West Nile (WNV) and Zika virus (ZIKV) NS1, while 4.3 and 3.2% were reactive to Rift Valley Fever virus (RVFV) N and Dengue virus-2 (DENV-2) NS1, respectively. Altogether, 21.6% of our samples were reactive to ≥1 flavivirus NS1s. Of the CHIKV E2 reactive samples, 8.5% were also reactive to at least one flavivirus NS1, and six samples were concurrently reactive to antigens of all three arbovirus groups, suggesting a high burden of multiple arbovirus infections for some participants. These insights suggest the presence of these four arbovirus families in Liberia with low and moderate rates of flavi- and alphavirus infections, respectively, in healthy adults. Further confirmational investigation, such as mosquito surveillance or other serological tests, is warranted and should be conducted before initiating additional flavivirus vaccination campaigns. The findings of these studies can help guide healthcare resource mobilization, vector control, and animal husbandry practices. Full article

Statins are among the most frequently prescribed medications. In addition to their well-established effectiveness in lowering total cholesterol, LDL, and triglycerides, statins have been described to have immunomodulatory and anti-inflammatory properties and have been associated with improved endothelial functions. Given the common use of statins, we sought to evaluate the effect of statins on some viral infections encountered by residents in tropical areas or by international travelers. A literature search was performed in PubMED/MEDLINE focusing on keywords that included statins and the viruses of interest, including SARS-CoV-2, influenza, yellow fever, dengue, Zika, tick-borne encephalitis, hemorrhagic fever viruses, hepatitis A, norovirus, hepatitis B, hepatitis C, measles, and herpesviruses; findings were synthesized for each virus into a summary. The effects of statins on viral infections vary depending on the specific virus. While some studies indicate potential benefits in chronic HBV and HCV infections, evidence regarding SARS-CoV-2 and influenza remains inconclusive due to mixed findings from observational studies and randomized controlled trials. The role of statins in other viral infections is largely unexplored, with preclinical data available for only a few viruses. Given the conflicting evidence, further prospective studies and randomized controlled trials are warranted to elucidate statins’ role in viral infections, particularly in modulating inflammation, endothelial dysfunction, and immune responses. Future research should aim to define the optimal patient populations, target viruses, statin types, and treatment durations that may confer benefits in specific viral infections. Full article

Birds are natural hosts for numerous zoonotic viral pathogens, including West Nile virus, which is transmitted by mosquitoes. During migration, birds can act as vectors for the geographic spread of viruses. WNV is endemic in Portugal, causing annual outbreaks, particularly in horses. Here, we report the first detection of an avian WNV strain isolated from a wild bird (Astur gentilis) collected in Portugal in mid-September 2024. Phylogenetic and phylogeographic analyses were conducted to trace the virus’s origin and potential transmission routes, integrating the obtained full-length genomic sequence with a dataset of WNV strains from Africa and Europe (1951–2024). Phylogenetic analysis of 92 WNV sequences spanning lineages 1–5 positioned the 2024 isolate within lineage 1a. Results obtained using phylodynamics-based analysis showed that this isolate likely originated in Africa and reached Portugal via Spain’s Cádiz coast, confirming previously described WNV dispersal patterns between Africa and Europe. The data suggest a migratory route from West Africa to Europe, extending through countries such as Senegal, Mauritania, Morocco, Portugal, Spain, Italy, and France, indicating a reciprocal flow of the virus back into Africa. These transmission routes match the migratory paths of Afro-Palearctic bird species, emphasizing the role of migratory birds in the long-distance spread of WNV. Full article

Zika virus (ZIKV) is a mosquito-borne flavivirus of the family Flaviviridae. The association between ZIKV and microcephaly was first described in Brazil in 2015. The risk of vertical transmission occurs in pregnant women with or without symptoms, and the risk of malformation appears to be worse when infection occurs in the first and second trimesters of pregnancy. The rate of vertical transmission varies from 26 to 65%, and not all fetuses develop malformations. The incidence of malformations resulting from transmission is uncertain, ranging from 6–8% in the US to 40% in Brazil. Congenital ZIKV syndrome is a set of clinical manifestations that can affect the fetus of a mother infected with ZIKV. The manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular changes, congenital contractures, early hypertension, and pyramidal and extrapyramidal signs. Other findings such as growth restriction and fetal miscarriage/death may also occur. Our aim in this article is to review the literature on mosquito transmission, clinical presentation, serologic diagnosis, intrauterine transmission, pre- and postnatal imaging diagnostic findings, and short- and long-term follow-up. Full article

ZIKA fever (ZIKAF) is an emerging mosquito-borne flavivirus illness in humans. Regarding the etiological agent, ZIKA virus (ZIKAV), though it is known to be distributed in the tropics, causing sporadic cases, its rapid global expansion with pandemic potential has raised global concern. Due to its abrupt emergence in South American countries, the Caribbean, and the Americas, the WHO declared ZIKA a public health emergency of international concern in 2016. ZIKAV usually causes mild infections; however, its recent unusual presentations of Guillen–Barré syndrome in adults and microcephaly in newborn babies of ZIKAV-infected mothers in Brazil has caused concern among global public health authorities. Certain mutations on virus genomes have been found to be correlated with clinical severity, and its unusual transmission routes through sexual and blood transfusions emphasize the necessity for understanding its virological determinants and impact. Its abrupt re-emergence in India (2018–2019), particularly in Gujarat (2016), Tamil Nadu (2017), Uttar Pradesh (2021), Maharashtra, Kerala (2021), and Karnataka (2023), has indicated the need for urgent measures to strengthen surveillance systems and design effective prevention and control measures in this country. Given the global concern around ZIKAV, here, we reviewed current knowledge about global ZIKAV genetic lineages vis à vis the situation in India and discussed future priorities for ZIKAV research in India for effectively designing control strategies. Full article

Background. Flaviviruses spread from endemic to non-endemic areas, causing illness in millions of people worldwide. The lack of effective therapies and the rapid expansion of flaviviral infections worldwide emphasize the importance of finding effective antivirals to treat such diseases. Objectives. To find out the potential broad-spectrum flavivirus inhibitors among previously reported inhibitors of DENV2/DENV4. Methods. The cytotoxicity of compounds was tested using WST-1 assay. The compounds were tested for their ability to inhibit the infection of DENV2, ZIKV, KUNV, and TBEV, and the most active compounds were also analyzed using the replicon-based assay. Interactions of one of the identified inhibitors with possible viral targets were studied using molecular dynamics simulations. Results. Two out of eight previously reported DENV2/DENV4 inhibitors demonstrated the ability to inhibit all studied viruses at low micromolar concentrations. Compound C6 demonstrated the ability to inhibit both DENV2 and TBEV. Compounds C1 (lycorine), C3 (mycophenolic acid), and C7 (vidarabine) were demonstrated as inhibitors of TBEV infection for the first time. Conclusions. Several compounds, previously described as inhibitors of DENV, are also able to inhibit other flaviviruses. This work is the first report on the anti-TBEV activity of lycorine (C1) and mycophenolic acid (C3), as well as vidarabine (C7). In addition, this is the first experimental confirmation of the antiviral activity of compound C5 and the lack of detectable antiviral activity of compound C8, demonstrating the necessity of experimental verification of the computational predictions. Full article