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J Virol, July 1998, p. 6113-6118, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Orphan Seven-Transmembrane Receptor Apj Supports the Entry of Primary T-Cell-Line-Tropic and Dualtropic Human Immunodeficiency Virus Type 1

Hyeryun Choe,1,2 Michael Farzan,1,2 Miriam Konkel,1,2 Kathleen Martin,3,4 Ying Sun,1,2 Luisa Marcon,1,2 Mark Cayabyab,1,2,3 Michael Berman,2 Martin E. Dorf,2 Norma Gerard,3,4 Craig Gerard,3,4 and Joseph Sodroski1,2,5,*

Division of Human Retrovirology, Dana-Farber Cancer Institute,1 Department of Pathology, Harvard Medical School,2 Perlmutter Laboratory, Children's Hospital,3 Departments of Medicine and Pediatrics, Beth Israel Hospital and Harvard Medical School,4 and Department of Immunology and Infectious Diseases, Harvard School of Public Health,5 Boston, Massachusetts 02115

Received 16 January 1998/Accepted 6 April 1998

Human immunodeficiency virus type 1 (HIV-1) enters target cells by sequential binding to CD4 and specific seven-transmembrane-segment (7TMS) coreceptors. Viruses use the chemokine receptor CCR5 as a coreceptor in the early, asymptomatic stages of HIV-1 infection but can adapt to the use of other receptors such as CXCR4 and CCR3 as the infection proceeds. Here we identify one such coreceptor, Apj, which supported the efficient entry of several primary T-cell-line tropic (T-tropic) and dualtropic HIV-1 isolates and the simian immunodeficiency virus SIVmac316. Another 7TMS protein, CCR9, supported the less efficient entry of one primary T-tropic isolate. mRNAs for both receptors were present in phytohemagglutinin- and interleukin-2-activated peripheral blood mononuclear cells. Apj and CCR9 share with other coreceptors for HIV-1 and SIV an N-terminal region rich in aromatic and acidic residues. These results highlight properties common to 7TMS proteins that can function as HIV-1 coreceptors, and they may contribute to an understanding of viral evolution in infected individuals.

* Corresponding author. Mailing address: JFB 824, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu.

J Virol, July 1998, p. 6113-6118, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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