The project
ARBOGEN in numbers:
7
Institutions
2
Work packages
1 437 614 €
Budget
3
Years
Context
Dengue virus is the most prominent mosquito-borne disease worldwide, with an ever-increasing burden. More than 14 million dengue cases were reported globally in 2024, including ~9,500 deaths. An important part of dengue disease burden is attributable to severe dengue (SD), one of the most serious forms observed in patients infected with dengue virus (DENV). Several factors have been proposed to be associated with the occurrence of severe dengue and could serve as predictors of disease progression including infection history, biochemical compounds found in the plasma, and host or virus genetics. Virus genetic determinants may play an important role in the severity of dengue disease, by enhancing viral pathogenesis and by limiting the effectiveness of diagnostics, antiviral, and vaccinal strategies targeting the virus. Despite the importance of DENV for Public Health, and even though sequencing capacity has increased in the wake of the Covid-19 pandemic, dengue virus genomes poorly documented relative to the number of infections recorded each year, with viral genomes obtained for less than 0.1% of reported infections in 2024. This deficit seriously undermines research on dengue virus and dengue virus disease and results in an alarming lack of information to guide Public Health strategies for the control of dengue and its increasing emergence.
Goals
ARBOGEN will take advantage of the unique extent of French territories to study the genetic determinants of the virus involved in the severity of dengue disease. ARBOGEN will address this question from two different angles :
(1) Viral pathogenesis : We will establish a trans-territorial network of public and private collaborators to collect DENV genomes from dengue case from across French territories. This effort will lead to the generation of a large set of DENV genomes, unparalleled in terms of size, quality and richness. This dataset will be the starting point for the in-depth investigation of the virus genetic determinants involved in the pathogenesis of severe dengue, and may help identify new therapeutic targets and markers to anticipate disease progression and inform patient care.
(2) Disease control methods: To investigate the virus genetic determinants impacting disease control methods, we will build a genomic tracking system for DENV, that will allow to share viral genomes via an an open online platform that will also include genomic data curated from public databases. Using the ARBOGEN platform, we will monitor circulating virus lineages globally, identify the mutations associated with dominant and emerging lineages, and assess their impact on current diagnostic, antiviral and vaccine strategies.
Coordination
ARBOGEN is coordinated by Dr Raphaëlle Klitting at the “Emerging Viruses Unit” in Marseille, headed by Prof. Xavier de Lamballerie (UVE : Inserm 1207 / UMR IRD 190 / Aix-Marseille Université / Institut de Recherche Biomédicale des Armées). Raphaëlle Klitting is a researcher with more than 10 years of experience in the genomics and evolution of emerging infectious diseases and with a keen interest in global Health. Her research now focuses on arbovirus genomics in close collaboration with the National Reference Center for arboviruses (virus sequencing strategies, genomic epidemiology and dispersal dynamics, and functional evolution).
Consortium and Network
ARBOGEN will rely on the Arbo-France network, which brings French metropolitan and overseas research teams in arbovirology. Seven institutions are involved in the ARBOGEN project, spanning six French Overseas Territories (FOT) and the metropole.
Expected results
- High-quality matched virus-patient dataset for severe dengue patients combining virus genomic data and patient metadata (collection time and clinical data)
- A platform allowing to share and explore dengue virus genomic data both from the project but also curated from public databases
- Online tools allowing to manipulate and analyse in real-time sets of genomic sequences of dengue virus selected by the user
- Contribution to research on dengue virus (pathogenesis, antiviral resistance, immune escape) and information of public health measures for the control of dengue disease
Funder
ARBOGEN is supported by MSDAVENIR a life sciences research support fund and financially operated by ANRS MIE (Emerging Infectious Diseases) which is an autonomous agence of Inserm with the aim of strengthening understanding, prevention and preparation for the emergence and re-emergence of infectious diseases.
Team
Work Packages
Two complementary Work packages were set up to achieve ARBOGEN goals :
WP1 - Pathogenesis
Question: Do mutations in dengue virus genome influence disease severity in dengue patients ?
Aim: Establish a trans-territorial network of cohorts covering all French overseas territories to collect data from severe and non-severe dengue cases, analyse matched virus-patient datasets, and perform experimental testing of putative determinants of pathogenesis
WP2 - Disease control methods
Question: Do mutations in dengue virus genome limit the effectiveness of disease control methods ?
Aim: Conduct a trans-territorial genomic tracking of dengue virus across FOTs, implement a platform for data sharing and analysis, create a compendium of the global genetic diversity of DENV lineages, assess the efficiency of diagnostics, antiviral drugs and immunisation methods on dominant and emerging virus lineages.
Linked initiatives
- LSDengue aims to identify new determinants of Severe Dengue (SD) to improve patient care. This complementary project is funded for 3 years by France 2030/ANRS MIE and coordinated by Pr André Cabié – CHU Martinique.
- CARBO is a study whose objective is to identify clinical, biological, virologic, immunologic and genetic factors associated with or predictive of severecomplications of arbovirus infections in a cohort of children and adults with confirmed arbovirus infections, in France.
- Arbo-France : a French network for the study of arboviruses whose objective is to facilitate preparedness and response to human and animal arbovirus epidemics in mainland France and in the overseas territories.
- DENGAFRICA : The overall aim of this project is to contribute to fill key scientific gaps related to dengue as a global health threat in Sub-Saharan Africa (SSA), through an integrated, interdisciplinary and multinational research approach. It will particularly aim to decipher: i) the burden of human disease, ii) the factors influencing dengue virus (DENV) transmission by local vectors in urban and peri-urban biotopes, and iii) the diversity of DENV strains isolated from human and Aedes mosquitoes’ populations through genomics.
ARBOGEN partners
UVE – Inserm 1207 – UMR IRD 190 – Marseille
Dr Raphaëlle Klitting – Principal Investigator
Institut Pasteur de Nouvelle-Calédonie
Pr Myrielle Dupont-Rouzeyrolle
Institut Pasteur de Guyane
Pr Dominique Rousset
CHU de La Réunion
Pr Marie-Christine Jaffar
CHU de Martinique
Pr André Cabié
CHU de Guadeloupe
Pr Raymond Césaire
Institut Louis Maladré
Pr Van-Mai CAO LORMEAU
In collaboration with
