title: Thermotropic lipid phase separation in the human immunodeficiency virus.
abstract: The presence of thermodependent lipid domains in the envelope of the human immunodeficiency virus (HIV) was studied. HIV was propagated in Hut-78 cells and purified by differential-gradient centrifugation. Since the virus was highly infectious in cell culture and Western blots of detergent-inactivated HIV showed envelope proteins when exposed to sera containing anti-HIV antibodies, this viral preparation was not deficient in 'spike' or 'knob' particles. Electron spin resonance (ESR) studies of intact HIV labeled with 5-nitroxide stearate (5-NS) indicated that a temperature-dependent lipid phase separation occurs with a high onset at approx. 42 degrees C and a low onset at approx. 15 degrees C. Cooling below 42 degrees C induces 5-NS clustering. Similar phase separations with high onsets at approx. 37-38 degrees C were previously identified in 5-NS labeled human erythrocytes (cholesterol/phospholipid (C/P) molar ratio = 0.90) and cholesterol-loaded (C/P = 0.85-0.98) rat liver plasma membranes. These were attributed to a temperature-sensitive redistribution of endogenous lipid components such that 5-NS is excluded from cholesterol-rich domains and tends to reside in cholesterol-poor domains at low temperatures. Since HIV has a lipid envelope with a similarly high C/P of 0.88 (Aloia et al. (1988) Proc. Natl. Acad. Sci. USA 85, 900-904), cholesterol-rich and cholesterol-poor domains also probably exist in HIV at physiologic temperatures. The reduced stability and infectivity of HIV noted on heating above 42 degrees C may be due, in part, to the abolition of these thermodependent domains.
authors.affiliation: Rees-Stealy Research Foundation, San Diego, CA 92101.
authors.forename: L M
authors.initials: LM
authors.lastname: Gordon
authors.forename: F C
authors.initials: FC
authors.lastname: Jensen
authors.forename: C C
authors.initials: CC
authors.lastname: Curtain
authors.forename: P W
authors.initials: PW
authors.lastname: Mobley
authors.forename: R C
authors.initials: RC
authors.lastname: Aloia
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002784:Cholesterol / Q000502:physiology; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006678:HIV / Q000648:ultrastructure*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008560:Membrane Fluidity; D008562:Membrane Glycoproteins / Q000502:physiology; D008563:Membrane Lipids / Q000502:physiology*; D008854:Microscopy, Electron; D013113:Spin Labels; D013816:Thermodynamics
chemical_list: D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D013113:Spin Labels; C005072:5-doxylstearic acid; D002784:Cholesterol