A polymorphism of the TIM-1 IgV domain: implications for the susceptibility to filovirus infection

Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):223-8. doi: 10.1016/j.bbrc.2014.10.144. Epub 2014 Nov 4.

Abstract

Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Human T-cell immunoglobulin and mucin domain 1 (TIM-1) is one of the host proteins that have been shown to promote filovirus entry into cells. In this study, we cloned TIM-1 genes from three different African green monkey kidney cell lines (Vero E6, COS-1, and BSC-1) and found that TIM-1 of Vero E6 had a 23-amino acid deletion and 6 amino acid substitutions compared with those of COS-1 and BSC-1. Interestingly, Vero E6 TIM-1 had a greater ability to promote the infectivity of vesicular stomatitis viruses pseudotyped with filovirus glycoproteins than COS-1-derived TIM-1. We further found that the increased ability of Vero E6 TIM-1 to promote virus infectivity was most likely due to a single amino acid difference between these TIM-1s. These results suggest that a polymorphism of the TIM-1 molecules is one of the factors that influence cell susceptibility to filovirus infection, providing a new insight into the molecular basis for the filovirus host range.

Keywords: Entry; Filovirus; Polymorphism; Receptor; Susceptibility; TIM-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Filoviridae / pathogenicity*
  • Filoviridae Infections / genetics*
  • Flow Cytometry
  • Genetic Predisposition to Disease
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Kidney / cytology
  • Kidney / virology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis
  • Polymorphism, Genetic*
  • Protein Structure, Tertiary
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • Sequence Homology, Amino Acid
  • Vero Cells

Substances

  • Membrane Glycoproteins
  • Receptors, Virus
  • Green Fluorescent Proteins