This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murakami, T.
Right arrow Articles by Yamamoto, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murakami, T.
Right arrow Articles by Yamamoto, N.

 Previous Article  |  Next Article 

Journal of Virology, September 1999, p. 7489-7496, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Inhibitory Mechanism of the CXCR4 Antagonist T22 against Human Immunodeficiency Virus Type 1 Infection

Tsutomu Murakami,1,dagger Tian-Yuan Zhang,2 Yoshio Koyanagi,1 Yuetsu Tanaka,3 Jin Kim,4 Yoichi Suzuki,1 Shigeru Minoguchi,5,9 Hirokazu Tamamura,6 Michinori Waki,7 Akiyoshi Matsumoto,7 Nobutaka Fujii,6 Hisatoshi Shida,5 James A. Hoxie,8 Stephen C. Peiper,2 and Naoki Yamamoto1,*

Department of Microbiology and Molecular Virology, Faculty of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519,1 University of the Ryukyus, Okinawa 903-0215,3 Institute for Virus Research, Kyoto University, Kyoto 606-01,5 Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501,6 Seikagaku Corporation, Tokyo 103,7 and Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606,9 Japan; University of Louisville, Louisville, Kentucky 402022; Genentech, South San Francisco, California 940804; and University of Pennsylvania, Philadelphia, Pennsylvania 191048

Received 8 February 1999/Accepted 28 May 1999

We recently reported that a cationic peptide, T22 ([Tyr5,12, Lys7]-polyphemusin II), specifically inhibits human immunodeficiency virus type 1 (HIV-1) infection mediated by CXCR4 (T. Murakami et al., J. Exp. Med. 186:1389-1393, 1997). Here we demonstrate that T22 effectively inhibits replication of T-tropic HIV-1, including primary isolates, but not of non-T-tropic strains. By using a panel of chimeric viruses between T- and M-tropic HIV-1 strains, viral determinants for T22 susceptibility were mapped to the V3 loop region of gp120. T22 bound to CXCR4 and interfered with stromal-cell-derived factor-1alpha -CXCR4 interactions in a competitive manner. Blocking of anti-CXCR4 monoclonal antibodies by T22 suggested that the peptide interacts with the N terminus and two of the extracellular loops of CXCR4. Furthermore, the inhibition of cell-cell fusion in cells expressing CXCR4/CXCR2 chimeric receptors suggested that determinants for sensitivity of CXCR4 to T22 include the three extracellular loops of the coreceptor.

* Corresponding author. Mailing address: Departments of Microbiology and Molecular Virology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81-3-5803-5178. Fax: 81-3-5803-0124. E-mail: yamamoto.mmb{at}med.tmd.ac.jp.

dagger Present address: Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892-0460.

Journal of Virology, September 1999, p. 7489-7496, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Murakami, T., Kumakura, S., Yamazaki, T., Tanaka, R., Hamatake, M., Okuma, K., Huang, W., Toma, J., Komano, J., Yanaka, M., Tanaka, Y., Yamamoto, N. (2009). The Novel CXCR4 Antagonist KRH-3955 Is an Orally Bioavailable and Extremely Potent Inhibitor of Human Immunodeficiency Virus Type 1 Infection: Comparative Studies with AMD3100. Antimicrob. Agents Chemother. 53: 2940-2948 [Abstract] [Full Text]  
  • Jones, J. W., Greene, T. A., Grygon, C. A., Doranz, B. J., Brown, M. P. (2008). Cell-Free Assay of G-Protein-Coupled Receptors Using Fluorescence Polarization. J Biomol Screen 13: 424-429 [Abstract]  
  • Blaak, H., Boers, P. H. M., Gruters, R. A., Schuitemaker, H., van der Ende, M. E., Osterhaus, A. D. M. E. (2005). CCR5, GPR15, and CXCR6 Are Major Coreceptors of Human Immunodeficiency Virus Type 2 Variants Isolated from Individuals with and without Plasma Viremia. J. Virol. 79: 1686-1700 [Abstract] [Full Text]  
  • Stalmeijer, E. H. B., van Rij, R. P., Boeser-Nunnink, B., Visser, J. A., Naarding, M. A., Schols, D., Schuitemaker, H. (2004). In Vivo Evolution of X4 Human Immunodeficiency Virus Type 1 Variants in the Natural Course of Infection Coincides with Decreasing Sensitivity to CXCR4 Antagonists. J. Virol. 78: 2722-2728 [Abstract] [Full Text]  
  • Liu, S., Boyer-Chatenet, L., Lu, H., Jiang, S. (2003). Rapid and Automated Fluorescence-Linked Immunosorbent Assay for High-Throughput Screening of Hiv-1 Fusion Inhibitors Targeting gp41. J Biomol Screen 8: 685-693 [Abstract]  
  • Chang, T. L.-Y., Francois, F., Mosoian, A., Klotman, M. E. (2003). CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from {alpha}-Defensin-1 HIV Inhibition. J. Virol. 77: 6777-6784 [Abstract] [Full Text]  
  • Ma, J., Kennedy-Stoskopf, S., Jaynes, J. M., Thurmond, L. M., Tompkins, W. A. (2002). Inhibitory Activity of Synthetic Peptide Antibiotics on Feline Immunodeficiency Virus Infectivity In Vitro. J. Virol. 76: 9952-9961 [Abstract] [Full Text]  
  • Bertolini, F., Dell'Agnola, C., Mancuso, P., Rabascio, C., Burlini, A., Monestiroli, S., Gobbi, A., Pruneri, G., Martinelli, G. (2002). CXCR4 Neutralization, a Novel Therapeutic Approach for Non-Hodgkin's Lymphoma. Cancer Res. 62: 3106-3112 [Abstract] [Full Text]  
  • Dragic, T. (2001). An overview of the determinants of CCR5 and CXCR4 co-receptor function. J. Gen. Virol. 82: 1807-1814 [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]  
  • Melikyan, G. B., Markosyan, R. M., Hemmati, H., Delmedico, M. K., Lambert, D. M., Cohen, F. S. (2000). Evidence That the Transition of HIV-1 Gp41 into a Six-Helix Bundle, Not the Bundle Configuration, Induces Membrane Fusion. JCB 151: 413-424 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»