Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with β-cyclodextrin inactivates and permeabilizes the virions

Evidence for virion-associated lipid rafts

David Graham, Elena Chertova, Joanne M. Hilburn, Larry O. Arthur, James E K Hildreth

Research output: Contribution to journalArticle

Abstract

Recent evidence suggests that human immunodeficiency virus type 1 (HIV-1) particles assemble and bud selectively through areas in the plasma membrane of cells that are highly enriched with glycosylphosphatidylinositol-anchored proteins and cholesterol, called lipid rafts. Since cholesterol is required to maintain lipid raft structure and function, we proposed that virion-associated cholesterol removal with the compound 2-hydroxy-propyl-β-cyclodextrin (β-CD) might be disruptive to HIV-1 and simian immunodeficiency virus (SIV). We examined the effect of β-CD on the structure and infectivity of cell-free virions. We found that β-CD inactivated HIV-1 and SIV in a dose-dependent manner and permeabilized the viral membranes, resulting in the loss of mature Gag proteins (capsid, matrix, nucleocapsid, p1, and p6) without loss of the envelope glycoproteins. SIV also lost reverse transcriptase (RT), integrase (IN), and viral RNA. IN appeared to be only slightly diminished in HIV-1, and viral RNA, RT, matrix, and nucleocapsid proteins were retained in HIV-1 but to a much lesser degree. Host proteins located internally in the virus (actin, moesin, and ezrin) and membrane-associated host proteins (major histocompatibility complex classes I and II) remained associated with the treated virions. Electron microscopy revealed that under conditions that permeabilized the viruses, holes were present in the viral membranes and the viral core structure was perturbed. These data provide evidence that an intact viral membrane is required to maintain mature virion core integrity. Since the viruses were not fixed before β-CD treatment and intact virion particles were recovered, the data suggest that virions may possess a protein scaffold that can maintain overall structure despite disruptions in membrane integrity.

Original languageEnglish (US)
Pages (from-to)8237-8248
Number of pages12
JournalJournal of Virology
Volume77
Issue number15
DOIs
StatePublished - Aug 2003

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
cyclodextrins
Cyclodextrins
Human immunodeficiency virus 1
virion
Virion
HIV-1
Cholesterol
cholesterol
Lipids
lipids
RNA-Directed DNA Polymerase
RNA-directed DNA polymerase
Integrases
Membranes
viruses
Viral RNA
Viruses
scaffolding proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with β-cyclodextrin inactivates and permeabilizes the virions : Evidence for virion-associated lipid rafts. / Graham, David; Chertova, Elena; Hilburn, Joanne M.; Arthur, Larry O.; Hildreth, James E K.

In: Journal of Virology, Vol. 77, No. 15, 08.2003, p. 8237-8248.

Research output: Contribution to journalArticle

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