Biology subjects

Dutartre, H.

Publications and source records attributed to Dutartre, H..

3 recordsLinked to original sources

bioRxiv2023

HTLV-1 Rex hijacks UPF1 in a CRM1 dependent manner, leading to NMD inhibition and revealing unexpected proviral roles of UPF1

The hijacking of CRM1 export is an important step of the retroviral replication cycle. Here, we investigated the consequences of this hijacking for the host. During HTLV-1 infection, we identified that this hijacking by the viral protein Rex favours the association between CRM1 and the RNA helicase UPF1, leading to a decreased affinity of UPF1 for cellular RNA and its nuclear retention. As a consequence, we found that the nonsense mediated mRNA decay (NMD), known to have an antiviral function, was inhibited. Corroborating these results, we described a similar process with Rev, the functional homolog of Rex from HIV-1. Unexpectedly, we also found that, for HTLV-1, this process is coupled with the specific loading of UPF1 onto vRNA, independently of NMD. In this latter context, UPF1 positively regulates several steps of the viral replication cycle, from the nuclear export of vRNA to the production of mature viral particles. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/545693v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1e91e61org.highwire.dtl.DTLVardef@1c9951borg.highwire.dtl.DTLVardef@15c6021org.highwire.dtl.DTLVardef@1ab35ff_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO During retroviral replication, the nuclear export unspliced vRNA is conducted via the hijacking of the exportin CRM1 by the viral protein Rex. In parallel, the RNA helicase UPF1 is naturally exported in a CRM1 dependent manner. In the cytoplasm it drives NMD, whose substrates include vRNA. Here we demonstrated that HTLV-1 Rex dependent hijacking of CRM1 is associated with the nuclear accumulation of UPF1 and the stabilization of the interaction between CRM1 and UPF1 (1). In this complex, UPF1 shows a decreased affinity for cellular RNA associated to NMD inhibition (2). We also observed that UPF1 is selectively loaded onto vRNA and stimulates vRNA export (3). In this context, UPF1 is driven in the viral particles (without NMD cofactors) where it plays critical role in virion assembly, maturation (4) and ultimately viral infection (5). Created in BioRender. PROCHASSON, L. (2025) https://BioRender.com/urj0cvo". C_FIG

molecular biology↗

bioRxiv2023

Tetraspanin CD82 maintains HTLV-1 biofilm polarization and is required for efficient viral transmission

The human T-lymphotropic virus type-1 (HTLV-1) is an oncogenic retrovirus whose transmission relies primarily on cell-to-cell contacts as cell-free viruses are poorly infectious. Among the intercellular transmission routes described, HTLV-1 biofilms are adhesive structures polarized at the cell surface that confine virions in a protective environment, which is believed to promote their simultaneous delivery during infection. Here, we show that several tetraspanins are enriched in HTLV-1 biofilms and incorporated into the viral envelope. However, we report that only tetraspanin CD82 interacts with HTLV-1 Gag which initiates its polarization into viral biofilms. Also, we 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. Our results highlight the crucial role of CD82 in the architectural organization of HTLV-1 biofilms and their transfer through intercellular contacts.

microbiology↗

bioRxiv2021

Immunoprofiling of HTLV-1-infected individuals shows altered innate cell responsiveness in HAM/TSP patients.

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. A biological blood factor allowing the prediction of the disease occurrence is so far not available. In this study, we analyzed innate immunity responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower responsiveness in dendritic cells to produce IFN. Moreover, we found higher production of IL-12 and Mip-1 by monocytes together with higher levels of IFN{gamma} produced by Natural Killer cells. These deregulations could represent a signature for progression towards HAM/TSP.

immunology↗