Mutations in the West Nile prM protein affect VLP and virion secretion in vitro

Virology. 2012 Nov 10;433(1):35-44. doi: 10.1016/j.virol.2012.07.011. Epub 2012 Jul 31.

Abstract

Mutation of the West Nile virus-like particle (WN VLP) prM protein (T20D, K31A, K31V, or K31T) results in undetectable VLP secretion from transformed COS-1 cells. K31 mutants formed intracellular prM-E heterodimers; however these proteins remained in the ER and ER-Golgi intermediary compartments of transfected cells. The T20D mutation affected glycosylation, heterodimer formation, and WN VLP secretion. When infectious viruses bearing the same mutations were used to infect COS-1 cells, K31 mutant viruses exhibited delayed growth and reduced infectivity compared to WT virus. Epitope maps of WN VLP and WNV prM were also different. These results suggest that while mutations in the prM protein can reduce or eliminate secretion of WN VLPs, they have less effect on virus. This difference may be due to the quantity of prM in WN VLPs compared to WNV or to differences in maturation, structure, and symmetry of these particles.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / metabolism
  • Glycosylation
  • Golgi Apparatus / metabolism
  • Models, Molecular
  • Mutation*
  • Protein Multimerization
  • Vero Cells
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / metabolism
  • Virion / physiology*
  • Virus Assembly / physiology*
  • Virus Replication
  • West Nile virus / pathogenicity
  • West Nile virus / physiology*

Substances

  • Viral Envelope Proteins
  • prM protein, Flavivirus