1. MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids.
- Author
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Moschonas GD, Delhaye L, Cooreman R, Hüsers F, Bhat A, Stylianidou Z, De Bousser E, De Pryck L, Grzesik H, De Sutter D, Parthoens E, De Smet AS, Maciejczuk A, Lippens S, Callewaert N, Vandekerckhove L, Debyser Z, Sodeik B, Eyckerman S, and Saelens X
- Subjects
- Humans, Nuclear Pore metabolism, HeLa Cells, HEK293 Cells, Herpesvirus 1, Human physiology, Herpesvirus 1, Human metabolism, Capsid metabolism, HIV-1 metabolism, HIV-1 physiology, Myxovirus Resistance Proteins metabolism, Myxovirus Resistance Proteins genetics, Biomolecular Condensates metabolism, Cytoplasm metabolism, Nuclear Pore Complex Proteins metabolism
- Abstract
Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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