Arboviruses such as Chikungunya virus (CHIKV), Dengue virus (DENV), West Nile virus (WNV) and Zika virus (ZIKV), which are transmitted by arthropods such as mosquitoes and ticks, pose a major public health challenge worldwide. Climate change, immigration, tourism and trade have contributed to their spread, with increased risk of autochthonous transmission also in Europe. Their persistence in human and non-human hosts has an impact on transmission dynamics and complicates containment efforts. For example, ZIKV, which was associated with congenital microcephaly during the 2015-2016 outbreak, persists in tissues such as the placenta and testes, influencing long-term disease progression and sexual virus transmission. The mosquito-borne CHIKV, DENV and WNV occasionally persist in tissues in the post-acute phase, leading to chronic joint pain, haemorrhagic fever and long-term neurological and renal disease, respectively. Tick-borne encephalitis virus and Toscana virus also show persistence in humans, associated with chronic and worsening disease. The mechanisms of persistence of arboviruses in humans, which are critical for viral evolution, disease dynamics and public health, are poorly defined. Understanding the persistence of these arboviruses is critical for improving strategies to prevent, treat and control these diseases.
GENESIS aims to comprehensively investigate the molecular mechanisms of arbovirus replication and persistence and their interactions with the host and to identify therapeutic targets. Using in vitro models, the viral replication pathways, tropism, the antiviral properties of host factors and their potential exploitation as drug targets are investigated. Using longitudinal patient samples, antibody responses to biomarkers of pathogenicity and persistence will be investigated, to assist in the design of new diagnostic platforms. The consortium will share resources and expertise and establish a network for data exchange and outreach. In line with the INF-ACT research program, GENESIS aims to improve the understanding of the persistence of these emerging viruses and to develop effective strategies for prevention, treatment and control.
The Consortium:
Mauro Pistello, University of Pisa, UNIPI
Massimo Pizzato, University of Trento, UNITN
Marisa Gariglio, University of Eastern Piedmont, UPO
Fabrizio Maggi, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, INMI
Alessandro Marcello, International Centre for Genetic Engineering and Biotechnology, ICGEB
Maria Lina Tornesello, National Cancer Institute “Fondazione Pascale” Napoli, INT-NA
Elisa Vicenzi, IRCCS San Raffaele Hospital, OSR
Concetta Beninati, Scylla Biotech SRL, SCYLLA
Mirko Cortese and Louis J.V. Galietta, Fondazione Telethon ETS, FTELE
Alessandra Brogi, DIESSE Diagnostica Senese, SPA, DIESSE
Publications:
Huerta V, Martin AM, Sarria M, Guirola O, Yero A, Ramos Y, Pupo D, Martin D, Marcello A, Chinea A. The low-density lipoprotein receptor-related protein-I is essential for Dengue virus infection. Viruses 2024 DOI: https://doi.org/10.3390/v16111692
Mekonnen F, Kahn BA, Nibert E, Munshea A, Tsega D, Endalamaw D, Tadesse S, Yismaw G, Lankir D, Ali J, Ulinici M, Orsini E, Susnjar U, Carletti T, Licastro D, Bitew M, Giovanetti M, Marcello A. Introduction of Dengue Virus Serotype 3 in the Afar Region, Ethiopia. Emerging Microbes & Infections 2024 https://doi.org/10.1080/22221751.2024.2429653
The project is supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT), project COC-1-2023-UNIPV – Unraveling the Molecular and Immunologic Mechanisms of Intrahost Persistence in Emerging and Re-Emerging Arboviral Infections – GENESIS, CUP F13C22001220007
