Journal article
Inhibition of HIV-1 infection by PEHMB involves perturbation of the viral co-receptor CCR5
Journal of neurovirology, Vol.12, pp.68-68
01 May 2006
Abstract
Neurological disease associated with HIV-1 infection of the central nervous system (CNS) remains a pressing problem, even in the face of successes achieved using the latest chemotherapeutic approaches to the treatment of systemic disease. For this reason, the development of compounds effective against HIV-1, particularly CCR5-using strains that predominate within infected cells in the CNS, remains a high priority. 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 notable activity against HIV-1 BaL, which uses CCR5 as a viral co-receptor. The potency of PEHMB in the presence of both virus and target cells led us to hypothesize that PEHMB interferes with viral binding and entry mechanisms. Results from flow cytometric analyses of HIV-1-susceptible cells exposed to PEHMB demonstrated increased CCR5 detection despite effective inhibition of HIV-1 BaL infection by PEHMB. We hypothesized that inhibition of HIV-1 BaL infection by PEHMB may involve perturbation of CCR5 conformation and/or localization within the plasma membrane. These changes interfere with interactions with HIV-1, while making CCR5 more accessible to detection by antibodies. Ongoing investigations are examining specific interactions between PEHMB and CCR5 that may cause changes in co-receptor availability, expression, internalization, or conformation that result in inhibition of HIV-1 infection. These studies are being used to 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
- Inhibition of HIV-1 infection by PEHMB involves perturbation of the viral co-receptor CCR5
- Creators
- Jin QianN ThakkarL SchlipfM FergusonS MillerT Kish-CataloneB WigdahlM LabibR RandoF Krebs
- Publication Details
- Journal of neurovirology, Vol.12, pp.68-68
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170151904721