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HIV entry in macrophages is dependent on intact lipid rafts

Macrophages are an important natural target cell for HIV-1, but previous studies of virus entry into these cells are limited, and the involvement of membrane cholesterol and lipid rafts is unknown. Cholesterol disruption of macrophage membranes using four pharmacological agents acting by different m...

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Autores principales: Carter, Gemma C., Bernstone, Laura, Sangani, Dhaval, Bee, Jessica Wynter, Harder, Thomas, James, William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103383/
https://www.ncbi.nlm.nih.gov/pubmed/19185899
http://dx.doi.org/10.1016/j.virol.2008.12.031
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author Carter, Gemma C.
Bernstone, Laura
Sangani, Dhaval
Bee, Jessica Wynter
Harder, Thomas
James, William
author_facet Carter, Gemma C.
Bernstone, Laura
Sangani, Dhaval
Bee, Jessica Wynter
Harder, Thomas
James, William
author_sort Carter, Gemma C.
collection PubMed
description Macrophages are an important natural target cell for HIV-1, but previous studies of virus entry into these cells are limited, and the involvement of membrane cholesterol and lipid rafts is unknown. Cholesterol disruption of macrophage membranes using four pharmacological agents acting by different mechanisms: methyl-β cyclodextrin, nystatin, filipin complex and Lovastatin, all significantly inhibited productive HIV entry and reverse transcription. The inhibitory effects of these drugs resulted in decreased virus release from infected cells, and could be substantially reversed by the addition of water-soluble cholesterol. The virus bound equally to cholesterol-disrupted cells even though HIV receptor expression levels were significantly reduced. Macrophage CD4 and CCR5 were found to partition with the detergent-resistant membranes with a typical raft-associating protein flotillin-1. HIV particles were observed co-localising with a marker of lipid rafts (CTB-FITC) early post infection. These data suggest that macrophage membrane cholesterol is essential for HIV entry, and implicate lipid raft involvement.
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spelling pubmed-71033832020-03-31 HIV entry in macrophages is dependent on intact lipid rafts Carter, Gemma C. Bernstone, Laura Sangani, Dhaval Bee, Jessica Wynter Harder, Thomas James, William Virology Article Macrophages are an important natural target cell for HIV-1, but previous studies of virus entry into these cells are limited, and the involvement of membrane cholesterol and lipid rafts is unknown. Cholesterol disruption of macrophage membranes using four pharmacological agents acting by different mechanisms: methyl-β cyclodextrin, nystatin, filipin complex and Lovastatin, all significantly inhibited productive HIV entry and reverse transcription. The inhibitory effects of these drugs resulted in decreased virus release from infected cells, and could be substantially reversed by the addition of water-soluble cholesterol. The virus bound equally to cholesterol-disrupted cells even though HIV receptor expression levels were significantly reduced. Macrophage CD4 and CCR5 were found to partition with the detergent-resistant membranes with a typical raft-associating protein flotillin-1. HIV particles were observed co-localising with a marker of lipid rafts (CTB-FITC) early post infection. These data suggest that macrophage membrane cholesterol is essential for HIV entry, and implicate lipid raft involvement. Elsevier Inc. 2009-03-30 2009-01-30 /pmc/articles/PMC7103383/ /pubmed/19185899 http://dx.doi.org/10.1016/j.virol.2008.12.031 Text en Copyright © 2008 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Carter, Gemma C.
Bernstone, Laura
Sangani, Dhaval
Bee, Jessica Wynter
Harder, Thomas
James, William
HIV entry in macrophages is dependent on intact lipid rafts
title HIV entry in macrophages is dependent on intact lipid rafts
title_full HIV entry in macrophages is dependent on intact lipid rafts
title_fullStr HIV entry in macrophages is dependent on intact lipid rafts
title_full_unstemmed HIV entry in macrophages is dependent on intact lipid rafts
title_short HIV entry in macrophages is dependent on intact lipid rafts
title_sort hiv entry in macrophages is dependent on intact lipid rafts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103383/
https://www.ncbi.nlm.nih.gov/pubmed/19185899
http://dx.doi.org/10.1016/j.virol.2008.12.031
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