Modeling the efficiency of filovirus entry into cells in vitro: Effects of SNP mutations in the receptor molecule

Kwang Su Kim, Tatsunari Kondoh, Yusuke Asai, Ayato Takada, Shingo Iwami

Research output: Contribution to journalArticlepeer-review

Abstract

Interaction between filovirus glycoprotein (GP) and the Niemann-Pick C1 (NPC1) protein is essential for membrane fusion during virus entry. Some single-nucleotide polymorphism (SNPs) in two surface-exposed loops of NPC1 are known to reduce viral infectivity. However, the dependence of differences in entry efficiency on SNPs remains unclear. Using vesicular stomatitis virus pseudotyped with Ebola and Marburg virus GPs, we investigated the cell-to-cell spread of viruses in cultured cells expressing NPC1 or SNP derivatives. Eclipse and virus-producing phases were assessed by in vitro infection experiments, and we developed a mathematical model describing spatial-temporal virus spread. This mathematical model fit the plaque radius data well from day 2 to day 6. Based on the estimated parameters, we found that SNPs causing the P424A and D508N substitutions in NPC1 most effectively reduced the entry efficiency of Ebola and Marburg viruses, respectively. Our novel approach could be broadly applied to other virus plaque assays.

Original languageEnglish
Article number1007612
JournalPLoS Computational Biology
Volume16
Issue number9
DOIs
Publication statusPublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Fingerprint Dive into the research topics of 'Modeling the efficiency of filovirus entry into cells in vitro: Effects of SNP mutations in the receptor molecule'. Together they form a unique fingerprint.

Cite this