Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host–pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, and other components of cellular or viral origin. Thus, they participate in intercellular communication, immune responses, and infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigate whether two pathogenic flaviviruses i.e., Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. The analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, is associated with exosomes. This observation could be confirmed under conditions of overexpression of recombinant NS1 from each flavivirus. Using different isolation methods (i.e., exosome isolation kit, size exclusion chromatography, Polyethylene Glycol enrichment, and ELISA capture), we showed that NS1 was present as a dimer at the surface of excreted exosomes, and that this association could occur in the extracellular compartment. This finding could be of major importance in a physiological context. Indeed, this capacity of NS1 to address EVs and its implication in the pathophysiology during Dengue or Zika diseases should be explored. Furthermore, exosomes that have demonstrated a natural capacity to vectorize NS1 could serve as useful tools for vaccine development.

Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes and may serve as unconventional secretory vesicles. Thus, they play a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses and stimulating immunity. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Owing to their tractability, the analysis of EVs from multiple biofluids has become a booming tool for monitoring various pathologies, from infectious to cancerous origins. In this review, we present an overview of exosome features and discuss their particular and ambiguous functions in infectious contexts. We then focus on their properties as diagnostic or therapeutic tools. In this regard, we explore the capacity of exosomes to vectorize immunogenic viral antigens and their function in mounting adaptive immune responses. As exosomes provide interesting platforms for antigen presentation, we further review the available data on exosome engineering, which enables peptides of interest to be exposed at their surface. In the light of all these data, exosomes are emerging as promising avenues for vaccine strategies.

The mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often fatal. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of four genetically related but antigenically distinct serotypes DENV-1–DENV-4. The growing burden of the four DENV serotypes has intensified both basic and applied research to better understand dengue physiopathology. Research has shown that the secreted soluble hexameric form of DENV nonstructural protein-1 (sNS1) plays a significant role in the pathogenesis of severe dengue. Here, we provide an overview of the current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. We discuss the potential use of sNS1 in future vaccine development and its potential to improve dengue vaccine efficiency, particularly against severe dengue illness.

Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, and many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes, including proteins, metabolites, nucleic acids, and lipids. Consequently, it is argued that exosomes may serve as unconventional secretory vesicles, playing a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses both qualitatively and quantitatively. Thus, the analysis of EVs from multiple biofluids, due to its ease of implementation, has become a booming tool for monitoring various pathologies, particularly cancer, as we shall outline further on. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Indeed, during a viral infection, the production of EVs and circulating exosomes is often enhanced to signal danger, stimulate immunity, and possibly serve as pathological biomarkers. Conversely, viruses can disrupt or hijack the exosome content and production. In this review, we discuss the particular and ambiguous functions of exosomes in infectious contexts. Furthermore, we explore the vectoring capacity of exosomes in light of the extensive literature examining their function in mounting adaptive immune responses. Exosomes provide an interesting platform for antigen presentation and could therefore serve as novel therapeutic targets or be used in vaccine strategies.

French Guiana experienced an unprecedented dengue epidemic during 2023–2024. Prior to the 2023–2024 outbreak in French Guiana, DENV-3 had not circulated in an epidemic manner since 2005. We therefore studied retrospectively the strains circulating in the French Territories of the Americas (FTA)—French Guiana, Guadeloupe, and Martinique—from the 2000s to the current epidemic. To this end, DENV-3 samples from the collection of the National Reference Center for Arboviruses in French Guiana (NRCA-FG) were selected and sequenced using next-generation sequencing (NGS) based on Oxford Nanopore Technologies, ONT. Phylogenetic analysis showed that (i) the 97 FTA sequences obtained all belonged to genotype III (GIII); (ii) between the 2000s and 2013, the regional circulation of the GIII American-I lineage was the source of the FTA cases through local extinctions and re-introductions; (iii) multiple introductions of lineages of Asian origin appear to be the source of the 2019–2021 epidemic in Martinique and the 2023–2024 epidemic in French Guiana. Genomic surveillance is a key factor in identifying circulating DENV genotypes, monitoring strain evolution, and identifying import events.

Background: Dengue virus type 2 (DENV2) is endemic to hyperendemic in the French territories of the Americas (FTAs), including French Guiana, Guadeloupe, Martinique, Saint-Barthelemy, and Saint-Martin. In 2023–2024, French Guiana, Martinique, and Guadeloupe experienced unprecedented dengue epidemics partly associated with this serotype. In response, we conducted a retrospective study of the diversity of DENV2 strains circulating in the FTAs from 2000 to 2024. Methods: To this end, we selected DENV2 samples from the collection at the National Research Center for Arboviruses in French Guiana (NRCA-FG) and sequenced them using Oxford Nanopore Technologies (ONT)-based next-generation sequencing (NGS). Results: Phylogenetic analysis revealed that (i) the 77 DENV2 sequences from the FTAs belong to two distinct genotypes—Asian American and Cosmopolitan; (ii) from the 2000s up to the 2019 epidemic in French Guiana, all sequenced strains belonged to the Asian American genotype; (iii) and from 2019 to 2020, strains circulating in Martinique and Guadeloupe belonged to the Cosmopolitan genotype, specifically the Indian subcontinent sublineage, while (iv) strains from the 2023–2024 outbreak in Martinique, Guadeloupe, and French Guiana fall within a distinct sublineage of the same genotype—Other Cosmopolitan. Additionally, we analyzed amino acid (AA) changes in FTA sequences compared to the Dengvaxia^® and Qdenga^® vaccines. The analysis of amino acid changes in FTA sequences compared to the vaccines (Dengvaxia^® and Qdenga^®) identified 42 amino acid changes in the prM/E regions (15 in the prM region and 27 in the E region) relative to CYD-2 Dengvaxia^® and 46 amino acid changes in the prM/E regions relative to Qdenga^®, including 16 in the prM region and 30 in the E region. Some of these AA changes are shared across multiple genotypes and sublineages, with 8 substitutions in the prM region and 18 in the E region appearing in both analyses. This raises questions about the potential impact of these changes on vaccine efficacy. Conclusion: Overall, these findings provide a current overview of the genomic evolution of DENV2 in the FTA, which is crucial for developing more effective prevention and control strategies and for selecting future vaccines tailored to circulating strains.