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

C. Inizan (1, 2, 3) , M. Caillet (1) , A. Desrames (1, 4) , A. David (5) , Perrine Bomme (6) , A. Mallet (6) , K. Bourdic (7) , O. Lambotte (7, 8) , F. Boufassa (9) , M. Mesel-Lemoine (10) , F. Tangy (10) , G. Pancino (11) , H. Mouquet (12) , T. Lagache (13, 14) , A. Dufour (13) , J.- Olivo-Marin (13) , F.A. Rey (1) , A. Saez-Cirion (5) , M.-I. Thoulouze (1)

1 Virologie Structurale - Structural Virology
2 SU - Sorbonne Université
3 URE-DA - Dengue et Arbovirose
4 BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge
5 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
6 CITECH - Microscopie ultrastructurale - Ultrapole
7 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
8 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
9 CESP - Centre de recherche en épidémiologie et santé des populations
10 Génomique virale et vaccination
11 Régulation des Infections Rétrovirales
12 Réponse humorale aux pathogènes
13 BIA - Analyse d'images biologiques - Biological Image Analysis
14 Columbia University [New York]

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.

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire; Virologie

C. Inizan, M. Caillet, A. Desrames, A. David, Perrine Bomme, et al.. HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes. 2021. ⟨pasteur-04121704⟩