Abstract |
We recently reported that a cationic peptide, T22 ([Tyr(5,12), Lys(7)]- 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.
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Authors | T Murakami, T Y Zhang, Y Koyanagi, Y Tanaka, J Kim, Y Suzuki, S Minoguchi, H Tamamura, M Waki, A Matsumoto, N Fujii, H Shida, J A Hoxie, S C Peiper, N Yamamoto |
Journal | Journal of virology
(J Virol)
Vol. 73
Issue 9
Pg. 7489-96
(Sep 1999)
ISSN: 0022-538X [Print] United States |
PMID | 10438838
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-HIV Agents
- Antimicrobial Cationic Peptides
- CXCL12 protein, human
- Chemokine CXCL12
- Chemokines, CXC
- HIV Envelope Protein gp120
- HIV envelope protein gp120 (305-321)
- Peptide Fragments
- Peptides
- Receptors, CXCR4
- T22 protein, synthetic
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Topics |
- Amino Acid Sequence
- Anti-HIV Agents
(metabolism, pharmacology)
- Antimicrobial Cationic Peptides
- Binding Sites
- Cell Fusion
- Chemokine CXCL12
- Chemokines, CXC
(metabolism)
- HIV Envelope Protein gp120
(metabolism)
- HIV-1
(drug effects, metabolism)
- HeLa Cells
- Humans
- Lipid Metabolism
- Molecular Sequence Data
- Peptide Fragments
(metabolism)
- Peptides
(metabolism, pharmacology)
- Receptors, CXCR4
(antagonists & inhibitors)
- Tumor Cells, Cultured
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