Search Results (524)

The expanding distribution and geographic range of mosquitoes have potentially contributed to increased flaviviral dissemination and transmission. Despite the growing burden of flaviviral infections, there are no effective antiviral treatments or vaccines, highlighting the need for novel therapeutic targets. Tetraspanins, a superfamily of transmembrane domain glycoproteins involved in cellular organization, signaling, and protein–protein interactions have been recognized as potential mediators of flaviviral infection and transmission. While their roles in vertebrate hosts have been explored, their involvement in flaviviral replication and dissemination within medically important vectors remains poorly understood. In this study, we investigated the role of arthropod tetraspanins in mosquito cells and extracellular vesicles (EVs) derived from cells infected with Zika virus (ZIKV) and dengue virus (serotype 2; DENV2). Among several of the tetraspanins analyzed, only CD151 was significantly upregulated in both mosquito cells and in EVs derived from ZIKV/DENV2-infected cells. RNAi-mediated silencing of CD151 led to a marked reduction in viral burden, suggesting its crucial role in flavivirus replication. Inhibition of EV biogenesis using GW4869 further demonstrated that EV-mediated viral transmission contributes to flavivirus propagation. Additionally, co-immunoprecipitation and immunofluorescence analyses revealed direct interactions between CD151 and ZIKV NS2B and DENV2 capsid proteins. Overall, our findings highlight the functional importance of mosquito CD151 in the replication and transmission of ZIKV and DENV2. This study provides new insights into the molecular mechanisms of flaviviral infection in mosquitoes and suggests that targeting vector tetraspanins may offer a potential approach to controlling mosquito-borne flaviviruses. Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and individual patient data meta-analysis of published cases of dengue-associated HLH. Eligible studies were identified through a search of PubMed and Scopus databases up to 5 March 2025. Clinical, laboratory, microbiological, treatment, and outcome data were extracted and analyzed. Results: A total of 133 patients from 71 studies were included. The median patient age was 18 years, and 56.8% were male. Common clinical features included fever (96.9%), cytopenias, organomegaly, and liver dysfunction. ALT elevation, jaundice, and hypofibrinogenemia were associated with mortality. DENV-1 was the most common serotype (57.4%) and was negatively associated with death. Overall, 19.3% of patients died. Multivariate analysis did not identify independent mortality predictors. Conclusions: Dengue-associated HLH predominantly affects young individuals and carries significant mortality. Key indicators of poor prognosis include hepatic dysfunction and the presence of shock or organ failure. Early recognition and prompt immunomodulatory treatment, particularly corticosteroids, may improve outcomes. Full article

Emerging RNA viruses such as influenza A virus (IAV), Zika virus (ZIKV), and dengue virus (DENV) continue to pose major challenges to animal and public health due to their high mutation rates, wide host ranges, and immune evasion strategies. In this study, we evaluated the in vitro antiviral activity of a marine bacterial extract derived from Parerythrobacter sp. M20A3S10 against IAV (H1N1; H3N2), influenza B virus (IBV), ZIKV, and DENV2. The extract demonstrated broad-spectrum antiviral effects with favorable selectivity indices across multiple host-derived epithelial cell lines. Notably, post-infection treatment significantly suppressed viral replication, suggesting a host-modulating or replication-inhibiting mechanism. While the extract’s active components have yet to be identified, bacteria from the Erythrobacteraceae family are known producers of bioactive metabolites with potential antiviral properties. These findings provide preliminary insight into the potential of marine-derived bacterial compounds in veterinary antiviral development and highlight the need for further characterization and in vivo validation. This work contributes to the understanding of virus–host interactions and the exploration of novel therapeutic strategies targeting the pathogenesis and immune modulation of veterinary RNA viruses. 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

Background: The evaluation of antiviral or vaccination strategies for the prevention of dengue infections in a traveler population would require extensive and complex studies. This prospective study aimed to identify a cohort of dengue naïve participants living in Medellín, a dengue endemic area, as a proxy for travelers and to determine the incidence of primary dengue virus (DENV) infection (symptomatic and asymptomatic) in this cohort. In Colombia, epidemic dengue waves occur every 3–4 years, with infected Aedes mosquitoes present in ~80% of the territory, including Medellín. Methods: Participants > 16 years of age, living in Medellín, were screened for anti-DENV immunoglobulin G (IgG). DENV seronegative participants were enrolled in this study. A serological anti-DENV survey was performed, with semiannual sample collections for up to 2 years. Acute DENV infections were evaluated by monitoring fever and testing for DENV nonstructural protein 1 and/or RNA. Results: Of the 4885 screened participants, 3008 participants (62%) were DENV seronegative and enrolled. Among them, 2263 (75%) completed this study, and 2644 (88%) had at least one serosurvey visit after baseline. Of those, 52 (2%) had laboratory-confirmed DENV seroconversion, and 19 (<1%) had febrile illness, but none had laboratory-confirmed DENV infection. Conclusions: This study identified a cohort of predominantly students, seronegative at study start, living in Medellín and serving as a proxy for a prospective DENV infection traveler population. Laboratory-confirmed primary DENV infection was found in 2% of participants, with <1% reporting febrile illnesses, meeting the WHO criteria for probable clinical dengue cases. Full article

Dengue virus serotypes 1-4 (DENV1-4) have spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the Wolbachia symbiont was proposed to suppress DENV transmission via the mosquito vectors Aedes aegypti and Aedes albopictus. Previously, we showed that a Wolbachia strain, wMelPop, suppresses DENV2 replication in the C6/36 albopictus cell line, with the mutant DENV2 appearing and replacing the wild type DENV2. In this study, we expanded the analysis to include replications of all DENV serotypes 1-4, effects of wAu Wolbachia in C6/36 cells, and wMelPop-influences on the Aag2 aegypti cell line. It was revealed that both wAu and wMelPop reduce all DENV infectious titers without dominant appearances of the mutant viruses, despite varied effects on the viral copy numbers. The host transcriptomic profiles by RNA-seq were also variously altered by wAu and wMelPop (ranging from 10 to 30%, Log₂FC > 2 or <−2, p < 0.05). Those transcripts were not further altered by DENV infection. In contrast, abundant transcriptomic alterations by DENV infection in naïve C6/36 and Aag2 cells were blocked by either wAu or wMelPop. These results indicate that Wolbachia prevents host cellular transcriptomic alterations which are induced by DENV infection, affecting the cellular homeostasis necessary for DENV replication. Full article

Dengue has been a serious public health concern in Nepal since the past few years, with concurrent big outbreaks occurring in 2022–2024. This cross-sectional study was conducted among febrile patients visiting hospitals in Mahottari district in southern Nepal. A total of 2141 dengue-suspected patients were investigated by routine laboratory assays and serological and molecular techniques, including real-time quantitative polymerase chain reaction (RT-qPCR). Among them, 455 (21.3%) were confirmed as dengue cases. The majority of dengue cases (435, 95.6%) had a primary dengue infection. The total bilirubin level was significantly higher in secondary dengue infection than in primary (p = 0.032). The major dengue virus (DENV) serotypes responsible for this outbreak were DENV-1 (45.5%) and DENV-2 (40.9%), while 13.6% patients had DENV-3 infection. DENV-3 infection showed a significantly higher viral load (median: 7.71 Log₁₀ copies/mL; range: 6.48–7.94) compared to DENV-1 (6.72 Log₁₀ copies/mL; 5.49–7.17) and DENV-2 (4.76 Log₁₀ copies/mL; 2.32–6.96). Adult patients exhibited a significantly higher viral load than children (p = 0.035). NS1- and IgM-positive as well as admitted patients had a higher viral load (p < 0.05). Co-circulation of multiple serotypes (DENV-1, -2, -3) was confirmed with the first introduction of DENV-1 and DENV-3 in Mahottari and surrounding areas in the 2023 outbreak. Identification of the circulating DENV serotypes is crucial to understanding the epidemiological trend and dynamics of population immunity. These findings underscore the need of nation-wide integrated surveillance, including genomic data generation, in Nepal for disease control, prevention, and potential vaccine implication. Full article

Dengue virus (DENV) remains a critical global health challenge, with no approved antiviral treatments currently available. The growing prevalence of DENV infections highlights the urgent need for effective therapeutics. Antiviral peptides (AVPs) have gained significant attention due to their potential to inhibit viral replication. However, traditional drug discovery methods are often time-consuming and resource-intensive. Advances in artificial intelligence, particularly deep generative models (DGMs), offer a promising approach to accelerating AVP discovery. This report provides a comprehensive assessment of the role of DGMs in identifying novel AVPs for DENV. It presents an extensive survey of existing antimicrobial and AVP datasets, peptide sequence feature representations, and the integration of DGMs into computational peptide design. Additionally, in vitro and in silico screening data from previous studies highlight the therapeutic potential of AVPs against DENV. Variational autoencoders and generative adversarial networks have been extensively documented in the literature for their applications in AVP generation. These models have demonstrated a remarkable capacity to generate diverse and structurally viable compounds, significantly expanding the repertoire of potential antiviral candidates. Additionally, this report assesses both the strengths and limitations of DGMs, providing valuable insights for guiding future research directions. As a data-driven and scalable framework, DGMs offer a promising avenue for the rational design of potent AVPs targeting DENV and other emerging viral pathogens, contributing to the advancement of next-generation therapeutic strategies. Full article

Dengue virus (DENV) infection is strongly associated with dengue hemorrhagic fever and dengue shock syndrome, both of which carry mortality risks. Addressing the urgent need for effective dengue therapeutics, we identified sofalcone, a gastroprotective agent with antioxidant and anti-inflammatory properties, as a potential inhibitor of DENV replication. Sofalcone demonstrated efficacy against all four DENV serotypes, with the dose inhibiting 50% (IC50) value of 28.1 ± 0.42 μM against viral replication of DENV serotype 2, without significant cytotoxicity. Additionally, sofalcone significantly improved survival rates and reduced viral titers in DENV-infected ICR-suckling mice. Mechanistically, sofalcone induced heme oxygenase-1 (HO-1) expression via the nuclear factor-erythroid 2-reated factor 2 (Nrf2) pathway, which in turn suppressed viral protease activity and restored antiviral interferon (IFN) responses. This included dose-dependent stimulation of IFN downstream antiviral genes such as 2′-5′-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3. Given its established clinical use as an anti-gastric ulcer drug, sofalcone offers promising potential for rapid application in treating DENV infection. Full article

Background: Dengue is a global health concern, with half of the world’s population at risk and no antiviral treatment available. This Phase 0 study investigated dengue infections among household contacts (HHCs) of dengue index cases (ICs) and assessed the feasibility of conducting a Phase 2 trial for a novel antiviral. Methods: Participants were enrolled in Nha Trang, Vietnam, from April 2022 to February 2023. Dengue ICs were identified within 72 h of fever onset, and their healthy adult HHCs enrolled within 48 h. Blood samples and questionnaires were collected bi-weekly for four weeks, with a follow-up visit on day 40. DENV RT-qPCR, NS1, and anti-DENV IgM/IgG ELISAs were performed. Results: Overall, 130 dengue ICs and 301 HHCs were enrolled, with 91.7% (276/301) completing all follow-up visits. Baseline anti-DENV IgG showed prior dengue infections in 262/301 HHCs (87.0%). Fifty HHCs were excluded from the HHC infection analysis based on evidence of a DENV infection (viral load [VL], NS1, IgM, and IgG results) at enrollment. During follow-up, 2.0% of HHCs (5/251) had DENV infections based on virological parameters (DENV RNA and/or NS1 positivity), and anti-DENV IgG/IgM seroconversion was detected in 7.2% (18/251). Conclusions: This study demonstrated the operational feasibility of a dengue IC-HHC design for a Phase 2 trial. Full article

Infections caused by dengue virus (DENV) result in significant morbidity and mortality. A proportion of infected individuals develop dengue haemorrhagic fever (DHF) characterized by circulatory collapse and multiorgan failure. Early detection of individuals likely to develop DHF could lead to improved outcomes for patients and help us use healthcare resources more efficiently. We identified proteins that are differentially regulated during early disease in peripheral blood mononuclear cells (PBMCs) of patients who subsequently developed DHF. Four dengue fever (DF), four DHF and two healthy control PBMCs were subjected to tandem mass tag mass spectrometry. Differentially regulated proteins were used to identify up- or down-regulated Gene Ontology pathways. One hundred and sixty proteins were differentially expressed in DENV-infected samples compared to healthy controls. PBMCs from DHF patients differentially expressed 90 proteins compared to DF; these were involved in down-regulation of platelet activation and aggregation, cell adhesion, and cytoskeleton arrangement pathways. Proteins involved in oxidative stress and p38 MAPK signalling were upregulated in DHF samples during early infection compared to DF. This study has identified 90 proteins differentially regulated in PBMCs that could potentially serve as biomarkers to identify patients at risk of developing DHF at an early disease stage. Full article

Coinfection with parasites and viruses can exacerbate disease transmission, outcomes and therapy. This study searched the Web of Science, PubMed, Scopus and JSTOR databases for publications on the prevalence of parasitic coinfection in people living with viruses from 1 January 2005 to 30 April 2022, and 356 studies were included and systematically reviewed. A meta-analysis was performed to assess the global prevalence of and factors potentially associated with parasitic infection (helminths and protozoa) in virus-infected people, and the infection burden was estimated. A variety of parasites (29 families, 39 genera, and 63 species) and viruses (8 kinds) were identified. The prevalence of parasitic coinfection in (all) virus-infected people was estimated to be 21.34% (95% CI 17.58–25.10, 5593 of 29,190 participants) and 34.13% (95% CI 31.32–36.94, 21,243/76,072 participants) for helminths and protozoa, respectively. Specially, in human immunodeficiency virus (HIV)-infected people, the global prevalence was 19.96% (95% CI 16.18–23.74) for helminths and 34.18% (95% CI 31.33–37.03) for protozoa, respectively. The global prevalence of protozoa was 41.79% (95% CI 15.88–67.69) in hepatitis B virus (HBV)-infected people and 17.75% (95% CI 3.54–31.95) in DENV-infected people, respectively. The global burden of parasitic infections in HIV-infected people was 7,664,640 for helminths and 13,125,120 for protozoa, respectively, and that in HBV- and dengue virus (DENV)-infected people was 137,019,428 and 629,952, respectively. The prevalence of parasitic coinfection at the family, genus, and species levels in virus- or HIV-infected people were comprehensively estimated and further analyzed by subgroups. Among the most commonly identified parasites, the five helminth genera with the highest prevalence in HIV-infected people were Schistosoma (12.46%, 95% CI 5.82–19.10), Ascaris (7.82%, 95% CI 6.15–9.49), Strongyloides (5.43%, 95% CI 4.11–6.74), Trichuris (4·82%, 95% CI 2.48–7.17) and Ancylostoma (2.79%, 95% CI 1.32–4.27), whereas the top five protozoan genera were Toxoplasma (48.85%, 95% CI 42.01–55.69), Plasmodium (34.96%, 95% CI 28.11–41.82), Cryptosporidium (14.27%, 95% CI 11.49–17.06), Entamoeba (12.33%, 95% CI 10.09–14.57) and Blastocystis (10.61%, 95% CI 6.26–14.97). The prevalence of parasitic coinfection in virus-infected people was associated with income level. The findings provide valuable global epidemiological information for informing normative guidance, improving surveillance, and developing public healthcare strategies. Full article

Dengue virus (DENV) threatens public health, especially in regions with tropical and subtropical climates. In 2024, the World Health Organisation reported 3.4 million confirmed dengue cases, with 16,000 severe cases and 3000 dengue-associated fatalities. The first licensed dengue vaccine, CYD-TDV (Dengvaxia^®,Sanofi-Pasteur, Paris, France), is recommended by the WHO only for individuals aged 9–45 years with a prior history of dengue infection. However, being vaccinated with Dengvaxia^® increases the risk of developing severe dengue infections in seronegative individuals. Recently, a second licensed dengue vaccine, Qdenga^®,Takeda, Singen, Germany), was approved and recommended by the WHO to be administered only in highly dengue-endemic countries, as it was not shown to elicit a robust immune response against DENV-3 and DENV-4 serotypes in dengue seronegative individuals. Due to an imbalance in immune response against all four DENV serotypes, there is a higher risk of developing the antibody-dependent enhancement (ADE) effect, which could lead to severe dengue. This review has identified mutations throughout the DENV genome that were demonstrated to attenuate the virulence of DENV in either in vitro or in vivo studies. Several amino acid residues within the DENV prM and E proteins were identified to play important roles in ADE and modifying these ADE-linked residues is important in the rational design of novel live-attenuated dengue vaccine candidates. This review provides current insights to guide the development of a novel live-attenuated tetravalent dengue vaccine candidate that is effective against all DENV serotypes and safe from ADE. The efficacy and safety of the live-attenuated vaccine candidate should be further validated in in vivo studies. Full article

In this study, we address the role of c-ABL (cellular Abelson Tyr kinase) in the cytoskeletal rearrangements induced by DENV (Dengue virus) infection in mammalian cells. Using the specific inhibitor imatinib and targeted RNA interference, we show that c-ABL is necessary for viral entry and subsequent ENV (DENV envelope protein) accumulation in infected cells. In addition, c-ABL targeting attenuates F-actin reorganization induced by DENV infection. Together with the involvement of c-ABL in endothelial dysfunction induced by DENV and host secreted factors, our findings strongly suggest that c-ABL is a potential host-targeted antiviral that could control DENV infection and/or its evolution to more severe forms of the disease. Full article

Dengue virus (DENV) is the most important arbovirus worldwide. In 2019, a significant increase in dengue cases was reported worldwide, resulting in a peak of imported cases in some European countries such as Spain. We aimed to describe travel-associated and locally acquired DENV strains detected in 2019 in the Catalonia region (northeastern Spain), a hotspot for dengue introduction in Europe. Through sequencing and phylogenetic analysis of the envelope gene, 75 imported viremic cases and two local strains were described. Autochthonous transmission events included an infection of a local mosquito with an imported dengue strain and a locally acquired human dengue infection from a locally infected mosquito. Overall, all four DENV serotypes and up to 10 different genotypes were detected. Phylogenetic analysis revealed transcontinental circulations associated with DENV-1 and DENV-2 and the presence of DENV-4 genotype I in Indonesia, where few cases had been previously described. A molecular study of the autochthonous events determined that local Ae. albopictus mosquitoes were infected by an African DENV-1 genotype V strain, while the locally acquired human case was caused by a DENV-3 genotype I of Asian origin. These findings underline the wide variability of imported strains and the high risk of DENV introduction into this territory, emphasizing the importance and usefulness of molecular characterization and phylogenetics for both local and global surveillance of the disease. Full article