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Journal of Virology, March 1999, p. 2343-2349, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Primary Human Immunodeficiency Virus Type 2 (HIV-2) Isolates, Like HIV-1 Isolates, Frequently Use CCR5 but Show Promiscuity in Coreceptor Usage

Andreas Mörner,1,* Åsa Björndal,1 Jan Albert,2 Vineet N. KewalRamani,3 Dan R. Littman,3 Rie Inoue,1 Rigmor Thorstensson,4 Eva Maria Fenyö,1 and Ewa Björling1

Microbiology and Tumorbiology Center (MTC), Karolinska Institute,1 and Department of Virology2 and Department of Immunology,4 Swedish Institute for Infectious Disease Control, Stockholm, Sweden, and Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Howard Hughes Medical Institute, New York University Medical Center, New York, New York3

Received 26 May 1998/Accepted 9 November 1998

Coreceptor usage of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to biological phenotype. The chemokine receptors CCR5 and CXCR4 are the major coreceptors that, together with CD4, govern HIV-1 entry into cells. Since CXCR4 usage determines the biological phenotype for HIV-1 isolates and is more frequent in patients with immunodeficiency, it may serve as a marker for viral virulence. This possibility prompted us to study coreceptor usage by HIV-2, known to be less pathogenic than HIV-1. We tested 11 primary HIV-2 isolates for coreceptor usage in human cell lines: U87 glioma cells, stably expressing CD4 and the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, and GHOST(3) osteosarcoma cells, coexpressing CD4 and CCR5, CXCR4, or the orphan receptor Bonzo or BOB. The indicator cells were infected by cocultivation with virus-producing peripheral blood mononuclear cells and by cell-free virus. Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5. In contrast, only two isolates, both from patients with advanced disease, used CXCR4 efficiently. These two isolates also promptly induced syncytia in MT-2 cells, a pattern described for HIV-1 isolates that use CXCR4. Unlike HIV-1, many of the HIV-2 isolates were promiscuous in their coreceptor usage in that they were able to use, apart from CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB coreceptors. Another difference between HIV-1 and HIV-2 was that the ability to replicate in MT-2 cells appeared to be a general property of HIV-2 isolates. Based on BOB mRNA expression in MT-2 cells and the ability of our panel of HIV-2 isolates to use BOB, we suggest that HIV-2 can use BOB when entering MT-2 cells. The results indicate no obvious link between viral virulence and the ability to use a multitude of coreceptors.

* Corresponding author. Mailing address: Microbiology and Tumorbiology Center (MTC), Karolinska Institute, Box 280, 171 77 Stockholm, Sweden. Phone: 46 8 7286320. Fax: 46 8 330744. E-mail: andreas.morner{at}mtc.ki.se.

Journal of Virology, March 1999, p. 2343-2349, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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