Co-assembly of viral envelope glycoproteins regulates their polarized sorting in neurons

PLoS Pathog. 2014 May 15;10(5):e1004107. doi: 10.1371/journal.ppat.1004107. eCollection 2014 May.


Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G) and fusion (NiV-F) glycoproteins of Nipah virus (NiV), a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G•NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G•NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Polarity / physiology*
  • Cells, Cultured
  • Embryo, Mammalian
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Neurons / physiology
  • Nipah Virus
  • Protein Sorting Signals
  • Protein Structure, Tertiary
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / metabolism*
  • Virus Assembly


  • Protein Sorting Signals
  • Viral Envelope Proteins