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Updated: Jan 15, 2026

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Human MX1 orchestrates the cytoplasmic sequestration of neosynthesized influenza A virus vRNPs
Joe McKellar1, Jimmy Cadènes1, Francisco García de Gracia1
1Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University, 34293 Montpellier, France.
Abstract:
Interferon-inducible Myxovirus resistance 1 (MX1) proteins are known to restrict influenza A virus (IAV) transcription/replication process. Herein, we show that this early restriction was only partial against human IAVs, with later replication stages more strongly inhibited. Murine (Mm)Mx1 induced an abnormal nuclear accumulation of the viral nucleoprotein (NP) at late time points postinfection. This block was observed to a lower extent with human (Hs)MX1; however, HsMX1 strongly impacted cytoplasmic trafficking of de novo synthesized viral ribonucleoprotein complexes (vRNPs). Indeed, live imaging experiments revealed a transient association of HsMX1 with Rab11a-associated vRNPs, which induced their clustering and their dynein-dependent retrograde transport toward the microtubule organizing center (MTOC). There, vRNPs remained sequestrated together with cellular cofactors YBX1 and Rab11a in large clusters, while MX1 dissociated from them. Dynein inhibition prevented the vRNP clustering and sequestration and significantly rescued infectious IAV production in the presence of HsMX1. In conclusion, this study provides evidence of IAV vRNPs being rerouted and accumulated away from the plasma membrane through the coordinated action of HsMX1 restriction factor, dynein, and the microtubule network.
Insights
Human MX1 protein restricts influenza A virus (IAV) by disrupting viral ribonucleoprotein complex (vRNP) transport. This leads to vRNP sequestration, inhibiting viral production.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Interferon-inducible Myxovirus resistance 1 (MX1) proteins inhibit influenza A virus (IAV) replication.
- The precise mechanisms of MX1 restriction, particularly by human (Hs)MX1, remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanism by which human MX1 restricts IAV replication.
- To investigate the role of MX1 in viral ribonucleoprotein complex (vRNP) trafficking.
Main Methods:
- Live imaging experiments to track vRNP and MX1 dynamics.
- Utilizing dynein inhibition to assess its role in vRNP transport.
- Assessing infectious IAV production under different conditions.
Main Results:
- Human MX1 partially inhibits early IAV replication but strongly affects later stages.
- HsMX1 induces cytoplasmic vRNP clustering and dynein-dependent retrograde transport toward the MTOC.
- vRNPs are sequestered with cellular factors YBX1 and Rab11a, and dynein inhibition rescues viral production.
Conclusions:
- Human MX1, dynein, and the microtubule network coordinate to sequester IAV vRNPs away from the plasma membrane.
- This mechanism represents a novel host-pathogen interaction impacting viral replication.
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