2. Academic Validation
  3. Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization

Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization

  • Sci Adv. 2022 Jul 22;8(29):eabn1440. doi: 10.1126/sciadv.abn1440.
Michael J Norris 1,  Monica L Husby 2,  William B Kiosses 1,  Jieyun Yin 1,  Roopashi Saxena 2,  Linda J Rennick 3,  Anja Heiner 4,  Stephanie S Harkins 1,  Rudramani Pokhrel 5,  Sharon L Schendel 1,  Kathryn M Hastie 1,  Sara Landeras-Bueno 1,  Zhe Li Salie 1,  Benhur Lee 6,  Prem P Chapagain 5 7,  Andrea Maisner 4,  W Paul Duprex 3,  Robert V Stahelin 2,  Erica Ollmann Saphire 1
Affiliations

Affiliations

  • 1 Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • 2 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA.
  • 3 Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • 4 Institute of Virology, Philipps University Marburg, Marburg, Germany.
  • 5 Department of Physics, Florida International University, Miami, FL 33199, USA.
  • 6 Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 7 Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
PMID: 35857835 DOI: 10.1126/sciadv.abn1440
Abstract

Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and Animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide Antiviral design. Here, we reveal that M proteins associate with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane. Using x-ray crystallography, electron microscopy, and molecular dynamics, we demonstrate that PI(4,5)P2 binding induces conformational and electrostatic changes in the M protein surface that trigger membrane deformation, matrix layer polymerization, and virion assembly.

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