Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry

J Virol. 2000 Dec;74(24):11972-6. doi: 10.1128/jvi.74.24.11972-11976.2000.


In addition to the CCR5 and CXCR4 chemokine receptors, a subset of primary human immunodeficiency virus type 1 (HIV-1) isolates can also use the seven-transmembrane-domain receptor APJ as a coreceptor. A previously identified ligand of APJ, apelin, specifically inhibited the entry of primary T-tropic and dualtropic HIV-1 isolates from different clades into cells expressing CD4 and APJ. Analysis of apelin analogues demonstrated that potent and specific antiviral activity was retained by a 13-residue, arginine-rich peptide. Antiviral potency was influenced by the integrity of methionine 75, which contributes to APJ-binding affinity, and by the retention of apelin residues 63 to 65. These studies demonstrate the ability of a small peptide ligand to block the function of APJ as an HIV-1 coreceptor, identify apelin sequences important for the inhibition, and provide new reagents for the investigation of the significance of APJ to HIV-1 infection and pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / virology*
  • Amino Acid Sequence
  • Apelin
  • Apelin Receptors
  • Carrier Proteins / physiology*
  • HIV-1 / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Molecular Sequence Data
  • Receptors, Dopamine D2 / physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Virus / physiology
  • Virus Replication


  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Receptors, Dopamine D2
  • Receptors, G-Protein-Coupled
  • Receptors, Virus