AEGiS-12IAC: A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 entry.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 entry.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:6 (abstract no. 11117)

Murakami T, Yamamoto N, Murakami T, Nakajima T, Waki M, Tamamura H, Fujii N
Depart. of Microbiology, Tokyo Medical and Dental University, Japan.

OBJECTIVES: To investigate whether anti-HIV peptide T22 specifically inhibits T cell line-tropic (T-tropic) HIV-1 infection mediated by its coreceptor CXCR4.

METHODS: We examined the effect of T22 on HIV-1 infection mediated by CD4- and coreceptor-expressing U87MG and HOS cells. Cell fusion assay was performed by coculture of HIV-1 Env-expressing HeLaS3 cells and CD4- and coreceptor-expressing NIH3T3 cells using a-complementation of b-galacotosidase. Interaction of T22 with a CXCR4 molecule was examined by effect of T22 on Ca2+ mobilization induced by PBSF/SDF-1 in CXCR4-expressing CHO cells, 12G5, an anti-CXCR4 monoclonal antibody binding to CXCR4-expressing MOLT-4 cells, and PBSF/SDF-1-induced chemotaxis of PHA-activated PBMC.

RESULTS: T22 specifically inhibited CXCR4-mediated HIV-1 infection and cell fusion. It also blocked Ca2+ mobilization induced by PBSF/SDF-1, 12G5 binding to CXCR4-expressing cells, and chemotaxis induced by PBSF/SDF-1 in a dose dependent manner.

CONCLUSION: We can described T22 as a small molecule CXCR4 antagonist and a potent inhibitor of T-tropic HIV-1 infection. This peptide represents a useful tool for investigating the entry emchanism of T-tropic HIV-1.

Keywords: AEGIS, HIV-1, T-Lymphocytes, Anti-HIV Agents, HIV Infections, Chemokines, CXC, Antigens, CD4, Peptides, Receptors, HIV, HIV Envelope Protein gp120, HIV, Cell Fusion, Cell Line, Antibodies, Monoclonal, stromal cell-derived factor-1alpha, antagonists & inhibitors, immunology, ICA12
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