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

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Sakaida, H.
	Articles by Uchiyama, T.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Sakaida, H.
	Articles by Uchiyama, T.

Previous Article | Next Article

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 isinitiated by the interaction between an envelope protein gp120of HIV-1, CD4, and one of the relevant coreceptors. To understandthe precise mechanism of the Env-mediated fusion and entry ofHIV-1, we examined whether the V3 region of gp120 of T-cell linetropic (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 theT-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linearV3 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 89.6strain (V3-89.6). FACScan analysis with a CXCR-4⁺ human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4monoclonal antibody (MAb), to CXCR-4 with different magnitudesin a dose-dependent manner, while none of the V3 peptides influencedbinding of an anti-CD19 MAb at all. Next, the effects of the V3peptides on SDF-1 $beta$ -induced transient increases in intracellularCa²⁺ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6)prevented Ca²⁺ mobilization. Furthermore, the three peptides inhibited infectionby T-tropic HIV-1 in a dose-dependent manner as revealed by anMTT assay and a reverse transcriptase assay, while the other peptideshad no effects. These results present direct evidence that theV3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptorCXCR-4 independently of the V1/V2 regions of gp120 or cellularCD4.

^* Corresponding author. Present address: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, 54Kawaracho, 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.

This article has been cited by other articles:

Sundstrom, M., White, R. L., de Parseval, A., Sastry, K. J., Morris, G., Grant, C. K., Elder, J. H. (2008). Mapping of the CXCR4 Binding Site within Variable Region 3 of the Feline Immunodeficiency Virus Surface Glycoprotein. J. Virol. 82: 9134-9142 [Abstract] [Full Text]
Vzorov, A. N., Dixon, D. W., Trommel, J. S., Marzilli, L. G., Compans, R. W. (2002). Inactivation of Human Immunodeficiency Virus Type 1 by Porphyrins. Antimicrob. Agents Chemother. 46: 3917-3925 [Abstract] [Full Text]
Basmaciogullari, S., Babcock, G. J., Van Ryk, D., Wojtowicz, W., Sodroski, J. (2002). Identification of Conserved and Variable Structures in the Human Immunodeficiency Virus gp120 Glycoprotein of Importance for CXCR4 Binding. J. Virol. 76: 10791-10800 [Abstract] [Full Text]
Yonezawa, A., Hori, T., Takaori-Kondo, A., Morita, R., Uchiyama, T. (2001). Replacement of the V3 Region of gp120 with SDF-1 Preserves the Infectivity of T-Cell Line-Tropic Human Immunodeficiency Virus Type 1. J. Virol. 75: 4258-4267 [Abstract] [Full Text]
Means, R. E., Matthews, T., Hoxie, J. A., Malim, M. H., Kodama, T., Desrosiers, R. C. (2001). Ability of the V3 Loop of Simian Immunodeficiency Virus To Serve as a Target for Antibody-Mediated Neutralization: Correlation of Neutralization Sensitivity, Growth in Macrophages, and Decreased Dependence on CD4. J. Virol. 75: 3903-3915 [Abstract] [Full Text]
Cormier, E. G., Persuh, M., Thompson, D. A. D., Lin, S. W., Sakmar, T. P., Olson, W. C., Dragic, T. (2000). Specific interaction of CCR5 amino-terminal domain peptides containing sulfotyrosines with HIV-1 envelope glycoprotein gp120. Proc. Natl. Acad. Sci. USA 97: 5762-5767 [Abstract] [Full Text]
Murakami, T., Zhang, T.-Y., Koyanagi, Y., Tanaka, Y., Kim, J., Suzuki, Y., Minoguchi, S., Tamamura, H., Waki, M., Matsumoto, A., Fujii, N., Shida, H., Hoxie, J. A., Peiper, S. C., Yamamoto, N. (1999). Inhibitory Mechanism of the CXCR4 Antagonist T22 against Human Immunodeficiency Virus Type 1 Infection. J. Virol. 73: 7489-7496 [Abstract] [Full Text]

J. Bacteriol.	Mol. Cell. Biol.	Microbiol. Mol. Biol. Rev.

Clin. Vaccine Immunol.	ALL ASM JOURNALS