Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry.
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.
Cayabyab
M
M
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Hinuma
S
S
Farzan
M
M
Choe
H
H
Fukusumi
S
S
Kitada
C
C
Nishizawa
N
N
Hosoya
M
M
Nishimura
O
O
Messele
T
T
Pollakis
G
G
Goudsmit
J
J
Fujino
M
M
Sodroski
J
J
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
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