Conference poster
Perturbation of the viral co-receptor CCR5 by NB325 inhibits HIV-1 infection
Journal of neurovirology, v 13, pp 99-99
01 Jan 2007
Abstract
Despite the successes achieved using the latest therapies effective against HIV-1-associated immunopathogenesis, neurological disease associated with HIV-1 infection of the central nervous system remains a pressing problem. For this reason, the development of compounds effective against HIV-1, specifically the CCR5-utilizing strains predominant in the brain, remains a high priority. Our efforts in this area focus on compounds that inhibit HIV-1 infection by interfering with the role of CCR5 in viral binding and entry. NB325, which is a biguanide-based compound, is characterized by low toxicity and notable activity against HIV-1 BaL, a CCR5-utilizing viral strain. Results from flow cytometric analyses of primary human peripheral blood mononuclear cells (PBMCs) demonstrated increased CCR5 detection following exposure to NB325 despite effective inhibition of HIV-1 BaL infection. Differences in CCR5 detection were also noted between quiescent PBMC sub-populations and cells activated with PHA-P. We hypothesize that inhibition of HIV-1 BaL infection by NB325 may involve perturbation of CCR5 within the plasma membrane. These changes interfere with interactions with HIV-1, and make CCR5 more accessible to detection by CCR5-specific antibodies. Our current mechanism of action studies are building on the observation that NB325 also interacts specifically with CXCR4 extracellular loop 2 (ECL2). Ongoing investigations are exploring similar interactions between NB325 and CCR5 that may cause changes in co-receptor availability, localization, and/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 to inhibit HIV-1 CNS infection.
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Details
- Title
- Perturbation of the viral co-receptor CCR5 by NB325 inhibits HIV-1 infection
- Creators
- K LozenskiN ThakkarS PassicT Kish-CataloneB WigdahlR RandoM LabibF Krebs
- Publication Details
- Journal of neurovirology, v 13, pp 99-99
- Publisher
- Taylor and Francis
- Number of pages
- 1
- Resource Type
- Conference poster
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000250754000191
- Other Identifier
- 991019170152704721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Virology