An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all new world hemorrhagic Fever arenaviruses

J Virol. 2012 Apr;86(7):4024-8. doi: 10.1128/JVI.06397-11. Epub 2012 Jan 25.

Abstract

Five New World (NW) arenaviruses cause human hemorrhagic fevers. Four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (hTfR1). Here we show that the fifth arenavirus, Chapare virus, similarly uses hTfR1. We also identify an anti-hTfR1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious Junín virus. Our data indicate that all NW hemorrhagic fever arenaviruses utilize a common hTfR1 apical-domain epitope and suggest that therapeutic agents targeting this epitope, including ch128.1 itself, can be broadly effective in treating South American hemorrhagic fevers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology*
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Arenaviruses, New World / physiology*
  • Cell Line
  • Down-Regulation*
  • Hemorrhagic Fevers, Viral / genetics
  • Hemorrhagic Fevers, Viral / immunology
  • Hemorrhagic Fevers, Viral / virology*
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, Transferrin / chemistry*
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / immunology*
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Sequence Alignment
  • Virus Internalization*

Substances

  • Antibodies
  • Antigens, CD
  • CD71 antigen
  • Receptors, Transferrin
  • Receptors, Virus