title: An orphan seven-transmembrane domain receptor expressed widely in the brain functions as a coreceptor for human immunodeficiency virus type 1 and simian immunodeficiency virus.
abstract: Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV) strains use CCR5 as a coreceptor, and many SIV strains can use CCR5 independently of CD4. In addition, several orphan seven-transmembrane receptors which can serve as HIV-1 and SIV coreceptors have been identified. Here we report that APJ, an orphan seven-transmembrane domain receptor with homology to the angiotensin receptor family, functions as a coreceptor for a number of HIV-1 and SIV strains. APJ was expressed widely in the human brain and in NT2N neurons. APJ transcripts were also detected by reverse transcription-PCR in the CD4-positive T-cell line C8166, but not in peripheral blood leukocytes, microglia, phytohemagglutinin (PHA)- or PHA/interleukin-2-stimulated peripheral blood mononuclear cells, monocytes, or monocyte-derived macrophages. The widespread distribution of APJ in the central nervous system coupled with its use as a coreceptor by some HIV-1 strains indicates that it may play a role in neuropathogenesis.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Edinger
authors.forename: T L
authors.initials: TL
authors.lastname: Hoffman
authors.forename: M
authors.initials: M
authors.lastname: Sharron
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Yi
authors.forename: W
authors.initials: W
authors.lastname: Choe
authors.forename: D L
authors.initials: DL
authors.lastname: Kolson
authors.forename: B
authors.initials: B
authors.lastname: Mitrovic
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: D
authors.initials: D
authors.lastname: Faulds
authors.forename: R G
authors.initials: RG
authors.lastname: Collman
authors.forename: J
authors.initials: J
authors.lastname: Hesselgesser
authors.forename: R
authors.initials: R
authors.lastname: Horuk
authors.forename: R W
authors.initials: RW
authors.lastname: Doms
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D015342:DNA Probes; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011784:Quail; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus / Q000378:metabolism / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*
chemical_list: C104575:APLNR protein, human; D000075244:Apelin Receptors; D015342:DNA Probes; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus