Journal article
PEHMB may inhibit HIV-1 infection independently of the functions of the chemokine receptor CXCR4
Journal of neurovirology, Vol.12, pp.80-81
01 May 2006
Abstract
Molecules that inhibit HIV-1 infection by disrupting interactions with the viral co-receptor CXCR4 may also interfere with normal chemokine receptor (CCR) functions. Within the central nervous system (CNS), CXCR4 and its ligand SDF-1 participate in neurogenesis, neuronal survival, and axonal pathfinding; inhibition of CXCR4 by a CCR inhibitor may adversely affect normal neuronal functions. For this reason, CCR inhibitors developed for use in the CNS should specifically inhibit HIV-1 infection while permitting normal CCR functions. Our efforts in this area have focused on compounds that appear to inhibit HIV-1 infection by interfering with interactions between the virus and cell surface proteins. Polyethylene hexamethylene biguanide (PEHMB) is characterized by low toxicity and considerable activity against HIV-1 IIIB, which uses CXCR4 as a viral co-receptor. The particular potency of PEHMB in the presence of both virus and target cells led us to hypothesize that PEHMB may interfere with viral binding and entry mechanisms. Flow cytometric analyses of HIV-1-susceptible cells exposed to PEHMB demonstrated that CXCR4 detection was decreased in an epitope-specific manner, indicating that CXCR4 remained on the cell surface despite its inability to support HIV-1 infection. These findings suggested that CXCR4-dependent inhibition of HIV-1 infection by PEHMB may not affect the normal functions of CXCR4 as a CCR. Ongoing investigations will explore the mechanism of PEHMB activity and its impact on normal CXCR4 functions in immune and neuroglial cells. These studies will facilitate the development of novel compounds that can be used safely in the CNS to inhibit HIV-1 infection.
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Details
- Title
- PEHMB may inhibit HIV-1 infection independently of the functions of the chemokine receptor CXCR4
- Creators
- N ThakkarJin QianL SchlipfM FergusonS MillerT Kish-CataloneB WigdahlM LabibR RandoF Krebs
- Publication Details
- Journal of neurovirology, Vol.12, pp.80-81
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170442004721