Search Results (269)

The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are used. In South America, HIV-1 epidemics intersect hyperendemic arboviruses, including dengue, Zika, chikungunya, and yellow fever, and regionally isolated pathogens, such as mammarenaviruses. These co-infections cause profound episodic immune activation and organ dysfunction that alter drug pharmacokinetics, disrupting healthcare access and adherence. These factors can compromise ART efficacy, promote resistance, and influence latent reservoir dynamics. This review synthesizes clinical and translational evidence of this intersection. We evaluate how emergent agents, such as capsid inhibitors (lenacapavir), long-acting injectables (cabotegravir/rilpivirine), maturation inhibitors (GSK3640254), and broadly neutralizing antibodies (bNAbs), perform in the context of co-endemic viral challenges. Specifically, we argue that therapeutic development must become “co-infection-aware” to progress toward a cure and achieve durable HIV-1 control. We provide a translational roadmap that explicitly incorporates co-infection endpoints into clinical trials, develops preclinical models that better reflect real-world viral exposures, and prioritizes implementation strategies that remain effective in the case of recurrent outbreaks. Integrating regional viral ecology into HIV-1 therapeutic research is therefore a necessary step toward developing interventions that are durable and effective on a global scale. Full article

Mosquito-borne flaviviruses, including Dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Yellow fever virus (YFV), and Zika virus (ZIKV), continue to present a significant threat to public health worldwide. In 2024, these viruses accounted for 11,717 reported cases in the United States and more than 7.6 million cases globally. As of early 2025, according to CDC data, 1830 cases of dengue had already been reported, with 1584 transmitted locally within the U.S. Despite the considerable burden that these diseases pose, no specific antiviral treatments exist. A very limited number of virus-specific vaccines have been licensed, such as those for YFV, JEV, and, with specific constraints, for DENV. To date, no pan-flavivirus vaccine is available. This review examines the potential of emerging vaccine platforms—particularly messenger RNA and virus-like particles—as promising tools in the pursuit of a broadly protective flavivirus vaccine. We analyze current strategies for inducing cross-neutralizing immune responses and discuss how these technologies could support the presentation of conserved quaternary epitope conformations, which are increasingly recognized as critical targets for establishing potent immune responses. We review key advances in virology, immune response, and immunogen delivery systems to highlight the potential for developing a pan-flavivirus vaccine. Full article

Mosquito-borne diseases, including dengue fever, chikungunya, and Zika, continue to pose a substantial global public health challenge. This is largely attributable to the absence of effective vaccines and the expanding distribution of vectors such as Aedes albopictus (Ae. albopictus). Repellents, therefore, remain a critical component of prevention strategies for disease prevention. However, existing formulations have notable limitations. Synthetic repellents such as DEET provide broad-spectrum efficacy but may raise safety concerns, especially at high concentrations. In contrast, botanical repellents, such as citronella and camphor oils, offer more favorable safety profiles but are restricted by short protection durations due to their high volatility. To overcome these drawbacks, this research developed a composite mosquito repellent through the strategic combination of DEET (5–15%), citronella oil (10–20%), and camphor oil (5–15%). This formulation leverages interactions across multiple olfactory pathways to simultaneously enhance efficacy and reduce the DEET concentration. Orthogonal experimental optimization identified an optimized formulation, Mix-3 (consisting of 15% DEET, 15% citronella oil, and 10% camphor oil in 75% ethanol), which achieved a mean complete protection time of 9.45 h. Mix-3 provided longer protection than 7% DEET (mean difference = 5.50 h, p < 0.001), 4.5% IR3535 (2.83 h, p < 0.001), 10% citronella oil (3.58 h, p < 0.001), and 15% DEET (6.50 h, p < 0.001). Catnip oil did not contribute significantly to repellency (p = 0.895). This study demonstrates that the rational combination of synthetic and botanical repellents effectively overcomes the limitations of single-agent formulations, providing a long-lasting and scalable approach for vector control. Full article

Arboviral diseases are emerging public health challenges in Burkina Faso, largely driven by the proliferation of Aedes aegypti mosquitoes in the environment. Effective surveillance of arbovirus circulation is critical to inform interventions. From August 2022 to June 2023, we implemented a comprehensive entomological surveillance platform in five sectors of Bobo-Dioulasso. Surveillance methods included oviposition traps to collect eggs, larval surveys in some concessions per sector conducted bimonthly, and adult mosquito collections using BG-Sentinel traps and Prokopack aspirators. Mosquito samples colonized by Ae. aegypti were identified morphologically, confirmed by conventional PCR, and screened by RT-PCR for dengue (DENV), chikungunya (CHIKV), yellow fever (YFV), and Zika (ZIKV) viruses. Molecular analysis detected dengue virus and yellow fever virus in mosquito pools from sector 22 and chikungunya virus in sectors 9 and 26; no Zika virus was found. This study demonstrates the successful establishment of an integrated entomological surveillance platform capable of capturing the spatial and temporal dynamics of arboviral vectors and virus circulation in Bobo-Dioulasso. The identification of active dengue and chikungunya transmission underlines the urgent need for sustained vector monitoring and targeted control strategies. Our approach provides a scalable model for arboviral disease surveillance and epidemic preparedness in West African urban settings. Full article

Arthropod-borne orthoflaviviruses, including dengue, Zika, Japanese encephalitis, yellow fever and West Nile viruses, pose a significant global public health threat, causing hundreds of millions of infections annually with severe clinical symptoms. However, the lack of effective vaccines and antiviral drugs, coupled with the biosafety risks associated with handling live highly pathogenic strains, hinders progress in antiviral research. Pseudovirus technology, which uses single-round infectious viral particles lacking replication competence, has thus gained prominence as a safe and versatile tool for antiviral research. This review systematically summarizes the construction, optimization, and applications of orthoflavivirus pseudoviruses in antiviral research. The primary construction strategies of orthoflavivirus pseudoviruses rely on multi-plasmid co-transfection of viral replicons and structural protein expression vectors, leveraging the host cell secretory pathway to mimic natural viral assembly and maturation. The core applications of pseudovirus technology are highlighted, including high-throughput screening and detection of neutralizing antibodies, identification of antiviral drugs targeting viral entry or replication, and evaluation of vaccine immunogenicity. Despite these strengths, the approach still faces limitations, such as incomplete simulation of native viral structures and batch-to-batch titer variability, which may affect the physiological relevance of findings. In summary, orthoflavivirus pseudovirus technology has become an essential platform in both basic virology research and translational medicine, providing critical insights and tools in the ongoing fight against arthropod-borne orthoflaviviruses diseases. Full article

Arthropod-borne viruses (arboviruses) such as dengue, chikungunya, Zika, and yellow fever pose significant global health risks, with mosquitoes from the Aedes genus as the primary vectors responsible for human transmission. The Republic of the Marshall Islands (RMI), particularly the urbanized areas of Kwajalein and Majuro atolls, has experienced multiple outbreaks of dengue, Zika, and chikungunya with substantial health and economic impacts. Vector control remains the most effective method for reducing disease risk, but comprehensive data on local mosquito vector composition, distribution, and abundance are needed to guide new, effective control efforts. From 2022 to 2024, we conducted a longitudinal baseline assessment of mosquito abundance and species composition on Ebeye and nearby islets in Kwajalein Atoll, RMI, using BG-Sentinel traps and ovitraps. Aedes aegypti was the most prevalent species, accounting for 58% of all adult females collected across study locations, with higher relative abundances on Ebeye than on northern islets (4.7 vs. 2.3 per trap/night). Aedes albopictus was more abundant on northern islets (0.7 vs. 3.2 per trap/night), and Culex quinquefasciatus showed similar abundances (1.2 vs. 1.7 per trap/night). Rainfall and anthropogenic factors, including water storage practices and housing density, influenced mosquito abundance. These findings provide multi-seasonal baseline data to support targeted vector control strategies in RMI. Full article

Apart from some information on dengue virus (DENV), there is limited data on the circulation of arboviruses in Burkina Faso. The aim of this study was to investigate antibody prevalence against six arboviruses in four regions of the country to document previous virus exposure. Serum samples collected between August 2018 and December 2022 from people infected with viral hepatitis B and C in Bobo-Dioulasso were used to detect IgG antibodies against DENV, Chikungunya virus (CHIKV), Zika virus (ZIKV), Yellow fever virus (YFV), Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) using commercial ELISA kits. A total of 1808 serum samples, accompanied by basic epidemiologic data (sex, age and residency) were included in this study. We observed an IgG antibodies seroprevalence of 75.4% for DENV, 30.8% for CHIKV, 2.9% for ZIKV, 1.2% for RVFV, 1.1% for CCHFV and 1.1% for YFV. Age, sex, and place of residence were significantly associated with seropositivity for DENV and age and sex with CHIKV seropositivity. The results suggested widespread circulation of DENV and CHIKV and possible circulation of CCHFV and RVFV in humans in Burkina Faso. The importance of strengthening arbovirus surveillance by including additional arboviruses in the diagnostic panel is emphasized. Full article

Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted by Aedes spp. mosquitoes, causing a spectrum of symptoms ranging from mild fevers and joint pain to severe damage to vital organs, including the kidneys, brain, and liver. Unfortunately, there are currently no specific treatments for these viruses. The NS2B/NS3 serine protease has been recognized as a crucial therapeutic target due to its pivotal role in viral replication. Herein, several molecular modeling techniques were employed to search for novel allosteric inhibitors against DENV and ZIKV NS2B/NS3 proteases from a set of 545 in-house compounds. Virtual screening based on molecular docking and MM/GBSA-based free energy calculations indicated that, among 545 derivatives, four compounds demonstrated high binding affinity against both targets, including two sulfonamide-vinyl sulfone hybrids (cpd48_e and cpd50_e), one sulfonamide-chalcone analog (cpd48), and one berberine-cinnamic acid derivative (DN071_f). Their molecular complexation was driven mainly by van der Waals forces rather than electrostatic attraction. Several residues at the enzyme allosteric site, particularly K74, L149, and N152 (DENV) and L76, I123, N152, and V155 (ZIKV), were identified as binding hotspots for the screened compounds. Drug-likeness predictions based on Lipinski’s rule of five further supported their potential as drug candidates. Overall, these findings provide valuable insights for the future design and development of novel antiviral drugs targeting the DENV and ZIKV NS2B/NS3 proteases. Full article

Dengue fever has become a major global public health challenge due to its rapidly in-creasing incidence. Rapid on-site detection of dengue virus (DENV) is critical for early diagnosis, timely patient isolation, and outbreak control. In this study, dengue virus serotype 2 (DENV-2), the predominant strain circulating in tropical and subtropical regions, was selected as the target pathogen. We established a one-tube rapid detection assay that integrates the HUDSON nucleic acid extraction-free protocol, reverse transcription recombinase-aided amplification (RT-RAA), and CRISPR/Cas12a-mediated trans cleavage activity. The method achieved a detection limit of 1 × 10² copies/μL for simulated infected samples and exhibited no cross-reactivity with other DENV serotypes (DENV-1, DENV-3, DENV-4) or with other arboviruses, including Zika, Japanese encephalitis, yellow fever, and chikungunya viruses. The assay demonstrated high sensitivity and specificity across various sample types, including mosquitoes, rodents, blood, and cultured cells, with results consistent with quantitative PCR (qPCR). Requiring only basic equipment such as a water bath, the system enables on-site detection of DENV-2 within 1 h. This simple, cost-effective, and reliable assay provides a practical tool for field-based DENV-2 surveillance and supports effective public health responses in resource-limited settings. Full article

Aedes aegypti is the primary urban vector for several important arboviruses, including dengue, chikungunya, yellow fever, and Zika viruses. Traditional dengue virus (DENV) surveillance relies on passive reporting of human cases, which often underestimates transmission due to asymptomatic or unreported infections. This study evaluated the utility of monitoring DENV in Ae. aegypti mosquitoes to improve detection of local dengue transmission and inform vector control strategies during the 2024 dengue epidemic in Puerto Rico. Mosquito surveillance was conducted in 15 neighborhoods within the San Juan metropolitan area where confirmed dengue cases had been recently reported. Adult female Ae. aegypti were collected weekly using Autocidal Gravid Ovitraps (AGO traps) placed within a 200 m radius of index cases. Pools of 1–20 mosquitoes were tested for DENV RNA and serotype using RT-PCR. Surveillance continued for up to 91 days in study areas, depending on virus detection. A total of 29,354 female Ae. aegypti were collected, of which 29,211 females were pooled (1–20 specimens per pool) into 3878 pools and analyzed. DENV was detected in 49 pools across 11 neighborhoods, with serotypes DENV-1, DENV-2, and DENV-3 identified. Multiple serotypes were sometimes detected in mosquitoes from the same neighborhood. Minimum infection rates and vector indices were higher during the epidemic than in previous inter-epidemic periods, and mosquito densities exceeded thresholds considered protective against outbreaks. Entomo-virological surveillance detected a greater variety and evenness of serotypes than passive human surveillance. These findings suggest that entomo-virological surveillance can complement passive case surveillance, providing a more comprehensive detection of DENV circulation. Integrating mosquito-based and human surveillance can improve outbreak detection, guide vector control, and aid in reducing dengue burden in affected communities. Full article

Background: Molecular mimicry contributes to the development of unwanted responses to self-antigens. Autoimmune phenomena have been observed in diseases caused by Aedes aegypti-transmitted arboviruses, but the occurrence of mimicry between salivary and human proteins has been unexplored. Methods: We used bioinformatic tools to determine if peptides from Aedes aegypti salivary proteins were present in the human proteome. We further characterized the potential of shared sequences to induce immunity by analyzing their predicted binding to MHC molecules and their occurrence in peptides from the Immune Epitope Database (IEDB). Results: We analyzed 9513 octapeptides from 29 Aedes aegypti salivary proteins against the human proteome and found 47 peptides identical to sequences from 52 human proteins, ranging in length from 8 to 18 amino acids. We found 302 matches of peptides predicted to bind with high affinity to MHC-I and MHC-II alleles associated with autoimmune diseases, and 14 human peptides containing shared sequences with Aedes aegypti salivary proteins validated as immunogenic in the IEDB. Conclusions: These results support the existence of molecular mimicry between Aedes aegypti salivary proteins and human antigens and provide a framework for studies to determine its contribution to responses directed to self-antigens in the context of arboviral infections. Full article

Omsk hemorrhagic fever is an acute zoonotic disease caused by Omsk hemorrhagic fever virus, a member of the genus Flavivirus (family Flaviviridae), with a reported case-fatality rate of approximately 3%. Historically confined to southwestern Siberia, ecological changes raise concerns about possible spread to non-endemic regions. Although no Omsk hemorrhagic fever cases have been reported in the Republic of Korea, the risk of accidental importation highlights the importance of establishing a reliable diagnostic protocol. We established and validated an institutionally developed diagnostic protocol employing real-time reverse transcription polymerase chain reaction targeting the NS2A and C genes of Omsk hemorrhagic fever virus. Primers and probes were designed from all available genomes to ensure broad strain coverage. Human ribonuclease P was used as an internal control to verify nucleic acid extraction and amplification. Using synthetic deoxyribonucleic acid fragments and in vitro-transcribed ribonucleic acid, assay performance was optimized, and analytical sensitivity was determined using probit analysis. The limits of detection were 74.50 copies/µL (threshold cycle 32.99) for NS2A and 70.41 copies/µL (threshold cycle 35.38) for C. Specificity testing using representative flaviviruses (West Nile virus, Yellow fever virus, Zika virus, St. Louis encephalitis virus, and Tick-borne encephalitis virus) and an alphavirus (Venezuelan equine encephalitis virus) demonstrated no cross-reactivity. The assay demonstrated high sensitivity, specificity, and reproducibility, supporting its potential application in national and international Omsk hemorrhagic fever virus surveillance systems. Full article

Climate change and the El Niño Southern Oscillation (ENSO) events have been increasingly linked to infectious disease outbreaks. While growing evidence has connected climate variability with systemic illnesses, the ocular implications remain underexplored. This study aimed to assess the relationships between ENSO-driven climate events and infectious diseases with ophthalmic consequences. A narrative review of 255 articles was conducted, focusing on infectious diseases influenced by ENSO and their associated ocular findings. 39 articles met criteria for full review, covering diseases such as dengue, zika, chikungunya, malaria, leishmaniasis, leptospirosis, and Rift Valley fever. Warmer temperatures, increased rainfall, and humidity associated with ENSO events were found to enhance vector activity and disease transmission. Ocular complications included uveitis, retinopathy, and optic neuropathy, but the specific disease findings varied by infectious disease syndrome. The climactic variable changes in response to ENSO events differed across diseases and regions and were influenced by geography, local infrastructure, and socioeconomic factors. ENSO event-related climate shifts significantly impact the spread of infectious diseases with ocular symptoms. These findings highlight the need for region-specific surveillance and predictive models that may provide insight related to the risk of ophthalmic disease during ENSO events. Further research is needed to clarify long-term ENSO effects and develop integrated strategies for systemic and eye disease detection, prevention, and management. Full article

Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4⁺ Th1 and CD8⁺ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8⁺ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article

The Orthoflavivirus genus belongs to the Flaviviridae family. Orthoflaviviruses include major clinically relevant arthropod-borne human viruses such as Dengue, Zika, yellow fever, West Nile and tick-borne encephalitis virus. These viruses pose an increasing threat to global health due to the expansion of arthropod habitats, urbanization, and climate change. While vaccines have been developed for certain orthoflaviviruses with varying levels of success, critical challenges remain in achieving broadly deployable vaccines that combine a robust safety profile with durable immunity against many current and emerging orthoflaviviruses. This review provides a snapshot of established and emerging vaccine platforms against orthoflaviviruses, with a particular emphasis on those leveraging the envelope glycoprotein E as the primary antigen. We examine the strengths and disadvantages of these different platforms in eliciting safe, durable, and robust orthoflavivirus immunity, and discuss how specific attributes such as multivalency, authentic epitope presentations, and logistical practicality can enhance their value in preventing orthoflavivirus infection and disease. Full article