Thermotropic lipid phase separation in the human immunodeficiency virus.
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.
Gordon
L M
LM
Rees-Stealy Research Foundation, San Diego, CA 92101.
Jensen
F C
FC
Curtain
C C
CC
Mobley
P W
PW
Aloia
R C
RC
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
D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D013113:Spin Labels; C005072:5-doxylstearic acid; D002784:Cholesterol