HIV-1 reprograms the migration of macrophages.

Abstract:

:Macrophages are motile leukocytes, targeted by HIV-1, thought to play a critical role in host dissemination of the virus. However, whether infection impacts their migration capacity remains unknown. We show that 2-dimensional migration and the 3-dimensional (3D) amoeboid migration mode of HIV-1-infected human monocyte-derived macrophages were inhibited, whereas the 3D mesenchymal migration was enhanced. The viral protein Nef was necessary and sufficient for all HIV-1-mediated effects on migration. In Nef transgenic mice, tissue infiltration of macrophages was increased in a tumor model and in several tissues at steady state, suggesting a dominant role for mesenchymal migration in vivo. The mesenchymal motility involves matrix proteolysis and podosomes, cell structures constitutive of monocyte-derived cells. Focusing on the mechanisms used by HIV-1 Nef to control the mesenchymal migration, we show that the stability, size, and proteolytic function of podosomes are increased via the phagocyte-specific kinase Hck and Wiskott-Aldrich syndrome protein (WASP), 2 major regulators of podosomes. In conclusion, HIV-1 reprograms macrophage migration, which likely explains macrophage accumulation in several patient tissues, which is a key step for virus spreading and pathogenesis. Moreover, Nef points out podosomes and the Hck/WASP signaling pathway as good candidates to control tissue infiltration of macrophages, a detrimental phenomenon in several diseases.

journal_name

Blood

journal_title

Blood

authors

Vérollet C,Souriant S,Bonnaud E,Jolicoeur P,Raynaud-Messina B,Kinnaer C,Fourquaux I,Imle A,Benichou S,Fackler OT,Poincloux R,Maridonneau-Parini I

doi

10.1182/blood-2014-08-596775

subject

Has Abstract

pub_date

2015-03-05 00:00:00

pages

1611-22

issue

10

eissn

0006-4971

issn

1528-0020

pii

blood-2014-08-596775

journal_volume

125

pub_type

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