Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection.
Publication/Presentation Date
9-1-1999
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.
Volume
73
Issue
9
First Page
7489
Last Page
7496
ISSN
0022-538X
Published In/Presented At
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. Journal of virology, 73(9), 7489–7496. https://doi.org/10.1128/JVI.73.9.7489-7496.1999
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
10438838
Department(s)
Administration and Leadership
Document Type
Article