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Journal of Virology, December 1998, p. 9763-9770, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

T-Tropic Human Immunodeficiency Virus Type 1 (HIV-1)-Derived V3 Loop Peptides Directly Bind to CXCR-4 and Inhibit T-Tropic HIV-1 Infection

Hitoshi Sakaida,1 Toshiyuki Hori,1 Akihito Yonezawa,1 Akihiko Sato,2 Yoshitaka Isaka,2 Osamu Yoshie,2 Toshio Hattori,1 and Takashi Uchiyama1,*

Laboratory of Virus Immunology, Research Center for Acquired Immunodeficiency Syndrome, Institute for Virus Research, Kyoto University, Kyoto 606,1 and Shionogi Institute for Medical Science, Osaka 566,2 Japan

Received 27 May 1998/Accepted 20 August 1998

Certain types of chemokine receptors have been identified as coreceptors for HIV-1 infection. The process of viral entry is initiated by the interaction between an envelope protein gp120 of HIV-1, CD4, and one of the relevant coreceptors. To understand the precise mechanism of the Env-mediated fusion and entry of HIV-1, we examined whether the V3 region of gp120 of T-cell line tropic (T-tropic) virus directly interacts with the coreceptor, CXCR-4, by using five synthetic V3 peptides: two cyclized V3 peptides (V3-BH10 and V3-ELI) which correspond to the V3 regions of the T-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linear V3 peptide (CTR36) corresponding to that of HIV-1 IIIB strain; and cyclized V3 peptides corresponding to that of the macrophage-tropic (M-tropic) HIV-1 ADA strain (V3-ADA) or the dualtropic HIV-1 89.6 strain (V3-89.6). FACScan analysis with a CXCR-4+ human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6 but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4 monoclonal antibody (MAb), to CXCR-4 with different magnitudes in a dose-dependent manner, while none of the V3 peptides influenced binding of an anti-CD19 MAb at all. Next, the effects of the V3 peptides on SDF-1beta -induced transient increases in intracellular Ca2+ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6) prevented Ca2+ mobilization. Furthermore, the three peptides inhibited infection by T-tropic HIV-1 in a dose-dependent manner as revealed by an MTT assay and a reverse transcriptase assay, while the other peptides had no effects. These results present direct evidence that the V3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptor CXCR-4 independently of the V1/V2 regions of gp120 or cellular CD4.

* Corresponding author. Present address: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo, Kyoto 606-8507, Japan. Phone: 81-75-751-3150. Fax: 81-75-751-3201. E-mail: uchiyata{at}kuhp.kyoto-u.ac.jp.

Journal of Virology, December 1998, p. 9763-9770, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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