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Journal of Virology, October 1998, p. 7934-7940, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Aimee L. Edinger,1 Trevor L. Hoffman,1 Matthew Sharron,1 Benhur Lee,1 Yanji Yi,2 Wonkyu Choe,3 Dennis L. Kolson,3 Branka Mitrovic,4 Yiqing Zhou,4 Daryl Faulds,4 Ronald G. Collman,2 Joseph Hesselgesser,4 Richard Horuk,4 and Robert W. Doms1,*

Department of Pathology and Laboratory Medicine,1 Department of Medicine (Pulmonary and Critical Care Division),2 and Department of Neurology,3 University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Immunology, Berlex Biosciences, Richmond, California 948044

Received 25 February 1998/Accepted 22 June 1998

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.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Pennsylvania, 806 Abramson, Philadelphia, PA 19104. Phone: (215) 898-0890. Fax: (215) 573-2883. E-mail: doms{at}mail.med.upenn.edu.

Journal of Virology, October 1998, p. 7934-7940, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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