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

Content Provider	PubMed Central
Author	Murakami, Tsutomu Zhang, Tian-yuan Koyanagi, Yoshio Tanaka, Yuetsu Kim, Jin Suzuki, Yoichi Minoguchi, Shigeru Tamamura, Hirokazu Waki, Michinori Matsumoto, Akiyoshi Fujii, Nobutaka Shida, Hisatoshi Hoxie, James A. Peiper, Stephen C. Yamamoto, Naoki
Copyright Year	1999
Abstract	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-1α–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.
Starting Page	7489
File Format	PDF
ISSN	10985514
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	9
Volume Number	73
Language	English
Publisher	American Society for Microbiology
Publisher Date	1999-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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

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