Abstract
BackgroundThe presence of cholesterol in the Human Immunodeficiency Virus (HIV) lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity. However, it is less well established whether other viral membrane lipids are also important for HIV infection.The ABCB4 protein is a phosphatidyl choline (PC) floppase that mediates transport of PC from the inner to the outer membrane leaflet. This property enabled us to modulate the lipid composition of HIV vectors and study the effects on membrane composition and infection efficiency.ResultsVirus generated in the presence of ABCB4 was enriched in PC and cholesterol but contained less sphingomyelin (SM). Viral titers were reduced 5.9 fold. These effects were not observed with an inactive ABCB4 mutant. The presence of the ABC transport inhibitor verapamil abolished the effect of ABCB4 expression on viral titers.The ABCB4 mediated reduction in infectivity was caused by changes in the viral particles and not by components co purified with the virus because virus made in the presence of ABCB4 did not inhibit virus made without ABCB4 in a competition assay.Incorporation of the envelope protein was not affected by the expression of ABCB4. The inhibitory effect of ABCB4 was independent of the viral envelope as the effect was observed with two different envelope proteins.ConclusionOur data indicate that increasing the PC content of HIV particles reduces infectivity.
Highlights
The presence of cholesterol in the Human Immunodeficiency Virus (HIV) lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity
Our data indicate that increasing the phosphatidyl choline (PC) content of HIV particles reduces infectivity
Because ABCB4 was expressed during vector production we investigated whether ABCB4 caused changes in the viral lipid composition and whether these changes were responsible for the reduced viral infectivity
Summary
The presence of cholesterol in the Human Immunodeficiency Virus (HIV) lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity. It is less well established whether other viral membrane lipids are important for HIV infection. The ABCB4 protein is a phosphatidyl choline (PC) floppase that mediates transport of PC from the inner to the outer membrane leaflet This property enabled us to modulate the lipid composition of HIV vectors and study the effects on membrane composition and infection efficiency. HIV membrane cholesterol has been shown to be important for viral integrity and function, depletion of cholesterol from HIV by incubation with cyclodextrin results in altered morphology and reduced infectivity of the viral particles [2]. Target cells with artificially increased levels of ceramide are less well infected by HIV because they endocytose viral particles more efficiently[7]
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