Protection against HIV-envelope-induced neuronal cell destruction by HIV attachment inhibitors

Protection against HIV-envelope-induced neuronal cell destruction by HIV attachment inhibitors We demonstrate that HIV attachment inhibitors (AIs) prevent HIV envelope-induced destruction of two neuronal cell lines (SH-SY5Y and BE(2)-M17) at low nanomolar concentrations. The fusion inhibitor enfuvirtide and the CCR5 inhibitors UK427,857 and TAK779 do not display protection activity, suggesting the involvement of Env/cell interaction site(s) distinct from the sites involved in the viral entry process. We surmise that by inducing conformation changes in the envelope, AIs likely obstruct novel interactions with a neuronal cell factor(s) required for induction of apoptosis. This antiretroviral class may therefore have the potential to inhibit HIV-induced neuron damage, thereby curtailing the increasing incidence of HIV-associated cognitive impairment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Protection against HIV-envelope-induced neuronal cell destruction by HIV attachment inhibitors

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Publisher
Springer Vienna
Copyright
Copyright © 2010 by Springer-Verlag
Subject
Biomedicine; Infectious Diseases; Medical Microbiology ; Virology
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-010-0644-x
Publisher site
See Article on Publisher Site

Abstract

We demonstrate that HIV attachment inhibitors (AIs) prevent HIV envelope-induced destruction of two neuronal cell lines (SH-SY5Y and BE(2)-M17) at low nanomolar concentrations. The fusion inhibitor enfuvirtide and the CCR5 inhibitors UK427,857 and TAK779 do not display protection activity, suggesting the involvement of Env/cell interaction site(s) distinct from the sites involved in the viral entry process. We surmise that by inducing conformation changes in the envelope, AIs likely obstruct novel interactions with a neuronal cell factor(s) required for induction of apoptosis. This antiretroviral class may therefore have the potential to inhibit HIV-induced neuron damage, thereby curtailing the increasing incidence of HIV-associated cognitive impairment.

Journal

Archives of VirologySpringer Journals

Published: May 1, 2010

References

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