title: Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry.
abstract: 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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cayabyab
authors.forename: S
authors.initials: S
authors.lastname: Hinuma
authors.forename: M
authors.initials: M
authors.lastname: Farzan
authors.forename: H
authors.initials: H
authors.lastname: Choe
authors.forename: S
authors.initials: S
authors.lastname: Fukusumi
authors.forename: C
authors.initials: C
authors.lastname: Kitada
authors.forename: N
authors.initials: N
authors.lastname: Nishizawa
authors.forename: M
authors.initials: M
authors.lastname: Hosoya
authors.forename: O
authors.initials: O
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Messele
authors.forename: G
authors.initials: G
authors.lastname: Pollakis
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: M
authors.initials: M
authors.lastname: Fujino
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000595:Amino Acid Sequence; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008969:Molecular Sequence Data; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus / Q000502:physiology; D014779:Virus Replication
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus