A tissue-intrinsic mechanism sensitizes HIV-1 particles for TLR-triggered innate immune responses
Sid Ahmed S, Zimmermann L, Imle A, Wuebben K, Tibroni N, Rauch-Wirth L, Münch J, Chlanda P, Graw F, Fackler OT (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 17
Article Number: 4209
Journal Issue: 1
DOI: 10.1038/s41467-026-72586-3
Abstract
In vivo, HIV-1 replicates within tissues, yet the impact of three-dimensional (3D) environments on viral spread remains unclear. Our laboratory previously showed that collagen-rich 3D extracellular matrix (ECM) imposes an Environmental Restriction to cell-free Virus Infectivity (ERVI). Here, we demonstrate that ERVI is mediated by adhesive ECM components assembled into tissue-like scaffolds. Transient interactions with collagen fibers rapidly diminish virion infectivity across diverse primary strains by impairing virus fusogenicity. Notably, collagen-experienced particles also induce a distinct antiviral transcriptional program and strong pro-inflammatory cytokine secretion in monocyte-derived macrophages. Mechanistically, collagen contact induces conformational changes in the viral glycoprotein Env, enhances its interaction with toll-like receptor 2 (TLR2), and promotes trafficking into TLR8-positive endosomes, thereby amplifying innate immune sensing. Thus, ERVI functions through a dual mechanism: reducing virion fusogenicity while increasing innate immune detection. These findings identify the biophysical properties of the ECM as a tissue-intrinsic arm of antiviral innate immunity.
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Germany (DE)How to cite
APA:
Sid Ahmed, S., Zimmermann, L., Imle, A., Wuebben, K., Tibroni, N., Rauch-Wirth, L.,... Fackler, O.T. (2026). A tissue-intrinsic mechanism sensitizes HIV-1 particles for TLR-triggered innate immune responses. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-72586-3
MLA:
Sid Ahmed, Samy, et al. "A tissue-intrinsic mechanism sensitizes HIV-1 particles for TLR-triggered innate immune responses." Nature Communications 17.1 (2026).
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