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

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Inizan, C. | Caillet, M. | Desrames, A. | David, A. | Bomme, Perrine | Mallet, A. | Bourdic, K. | Lambotte, O. | Boufassa, F. | Mesel-Lemoine, M. | Tangy, F. | Pancino, G. | Mouquet, H. | Lagache, T. | Dufour, A. | Olivo-Marin, J.- | Rey, F.A. | Saez-Cirion, A. | Thoulouze, Marie-Isabelle

Edité par CCSD -

ABSTRACT Collective transmission via structures containing several virions has recently emerged as a highly efficient mode of viral spread. Here, we demonstrate that HIV-1 spreads between T lymphocytes in the form of viral particles colonies that are concentrated and sheltered in an extracellular matrix (ECM) lattice enabling their collective transmission upon cell contacts. Intrinsically, ECM-clustered viruses infect T lymphocytes more efficiently than individual viral particles. They preserve HIV-1 transmission from antiretroviral treatment (ArT) and potent broadly neutralizing antibodies. We also show that collagen induced by HIV-1 infection controls the clustering of virions and their collective spread, thereby enhancing infectivity. CD4+ T cells from HIV-1-infected patients produce and transmit ECM-virus clusters, supporting that they could be involved in vivo . This study provides new insights into modes of HIV-1 transmission and identifies a novel fundamental role for collagen in this process. HIV-1 spread via ECM-virus clusters may have important implications for viral dissemination and persistence, including during therapy.

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