The human T-lymphotropic virus type-1 (HTLV-1) is the most potent oncogenic virus known to date, with a minimal estimation of 5 to 10 million people infected worldwide. Although most people remain asymptomatic following HTLV-1 exposure, chronic infections can lead to aggressive pathologies with poor prognoses such as adult T-cell leukemia (ATL) or progressive inflammatory disorders like HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In vivo, HTLV-1 is primarily detected in CD4(+) T-cells and to a lesser extent in CD8(+) T-cells, monocytes, or dendritic cells. In the early stages of infection, HTLV-1 dissemination within its host is believed to rely mostly on cell-to-cell contacts, as cell-free viruses are poorly infectious. Past studies unveiled a novel mechanism of HTLV-1 intercellular transmission based on the remodeling of the host-cell extracellular matrix and the generation of cell-surface viral assemblies whose structure, composition, and function resemble bacterial biofilms. These polarized aggregates of infectious virions, identified as viral biofilms, allow the bulk delivery of viruses to target cells and may help to protect virions from immune attacks. However, the molecular and functional description of viral biofilms is still in its infancy, although it is crucial to fully decipher retroviruses pathogenesis. Here, we explored the function of cellular tetraspanins (CD9, CD81, CD82) that we detected in the envelope of HTLV-1 particles within biofilms. Our results demonstrate that CD82 maintains HTLV-1 biofilm polarization and favors viral transmission, as its silencing induces a complete reorganization of viral clusters at the cell surface and reduces the ability of infected T-cells to transmit the virus. Therefore, we highlight a crucial role for specific tetraspanins in the architectural organization of HTLV-1 biofilms and their subsequent transfer through intercellular contacts.
- Étude de la biogénèse, de la composition, et de la transmission des biofilms viraux induits par le virus HTLV-1
- Coline Arone - 33UDM_INST___HR10S03606
- Delphine MuriauxHélène DutartreCécile Gauthier-Rouvière [Président]Boyan Grigorov [Rapporteur]Nolwenn Jouvenet [Rapporteur]Olivier Schwartz
- École doctorale Sciences Chimiques et Biologiques pour la Santé (Montpellier ; 1992-....)
- Doctoral
- 99245216909311
- IRIM - Institut de Recherche en Infectiologie de Montpellier
- French
- Theses and HDR
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