HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes

Inizan, Catherine; Caillet, Marina; Desrames, Alexandra; David, Antonio; Bomme, Perrine; Mallet, Adeline; Bourdic, Katia; Lambotte, Olivier; Boufassa, Faroudy; Mesel-Lemoine, Mariana; Tangy, Frédéric; Pancino, Gianfranco; Mouquet, Hugo; Lagache, Thibault; Dufour, Alexandre; Olivo-Marin, J.-C.; Rey, Françoise; Sáez‐Cirión, Asier; Thoulouze, María-Isabel

doi:10.1101/2021.09.27.461933

Cited by 2 publications

(3 citation statements)

References 86 publications

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“…Clusters of mature HIV-1 particles resembling biofilms were also detected at the surface of infected MOLT T-lymphoblastic cells 30 , at the surface of primary CD4(+) T-cells upon in vitro HIV-1 infection 66,67 , and at the surface of CD4(+) T-cells from HIV-1-infected patients 66 . Virions aggregation significantly increases the chances of multiple viral genomes being jointly delivered to target cells, as shown recently for VSV 68 and HIV-1 66 , which demonstrates the ability of enveloped viruses to establish collective infectious units. Accordingly, viral biofilms account for 80% of HTLV-intercellular transmission in vitro 24 , and our results further support the importance of the collective transmission of clustered virions.…”

Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 92%

“…Finally, we demonstrated that the CD82-dependent clustering of viral particles within TEMs at the cell surface is a key parameter in HTLV-1 cell-to-cell transmission (Figure 6). Early electron microscopy studies revealed that other viruses could also form viral aggregates at the cell surface resembling viral biofilms, including IAV 64 , vesicular stomatitis virus 65 , and HIV-1 52,66 . Clusters of mature HIV-1 particles resembling biofilms were also detected at the surface of infected MOLT T-lymphoblastic cells 30 , at the surface of primary CD4(+) T-cells upon in vitro HIV-1 infection 66,67 , and at the surface of CD4(+) T-cells from HIV-1-infected patients 66 .…”

Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 99%

“…Early electron microscopy studies revealed that other viruses could also form viral aggregates at the cell surface resembling viral biofilms, including IAV 64 , vesicular stomatitis virus 65 , and HIV-1 52,66 . Clusters of mature HIV-1 particles resembling biofilms were also detected at the surface of infected MOLT T-lymphoblastic cells 30 , at the surface of primary CD4(+) T-cells upon in vitro HIV-1 infection 66,67 , and at the surface of CD4(+) T-cells from HIV-1-infected patients 66 . Virions aggregation significantly increases the chances of multiple viral genomes being jointly delivered to target cells, as shown recently for VSV 68 and HIV-1 66 , which demonstrates the ability of enveloped viruses to establish collective infectious units.…”

Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 99%

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

Arone

Martial

Gaillard

et al. 2023

Preprint

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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.

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Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 92%

Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 99%

Section: This Interaction Was Proposed To Account For Htlv-1 Env Loca...mentioning

confidence: 99%

See 1 more Smart Citation

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

Arone

Martial

Gaillard

et al. 2023

Preprint

Self Cite

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show abstract

HTLV-1 biofilm polarization maintained by tetraspanin CD82 is required for efficient viral transmission

Arone,

Martial,

Burlaud-Gaillard

et al. 2023

mBio

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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 the tetraspanin CD82 interacts with HTLV-1 Gag proteins which initiates their 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 and its glycosylation state in the architectural organization of HTLV-1 biofilms and their subsequent transfer through intercellular contacts. IMPORTANCE In the early stages of infection, human T-lymphotropic virus type 1 (HTLV-1) dissemination within its host is believed to rely mostly on cell-to-cell contacts. 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, viral biofilms’ molecular and functional description is still in its infancy, although it is crucial to fully decipher retrovirus pathogenesis. Here, we explore the function of cellular tetraspanins (CD9, CD81, CD82) that we detect inside HTLV-1 particles within biofilms. Our results demonstrate specific roles for CD82 in the cell-surface distribution and intercellular transmission of HTLV-1 biofilms, which we document as two essential parameters for efficient viral transmission. At last, our findings indicate that N-glycosylation of cell-surface molecules, including CD82, is required for the polarization of HTLV-1 biofilms and for the efficient transmission of HTLV-1 between T-lymphocytes.

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HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes

Cited by 2 publications

References 86 publications

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

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

HTLV-1 biofilm polarization maintained by tetraspanin CD82 is required for efficient viral transmission

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