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.

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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