The HIV lipidome: A raft with an unusual composition

Abstract

The lipids of enveloped viruses play critical roles in viral morphogenesis and infectivity. They are derived from the host membranes from which virus budding occurs, but the precise lipid composition has not been determined for any virus. Employing mass spectrometry, this study provides a quantitative analysis of the lipid constituents of HIV and a comprehensive comparison with its host membranes. Both a substantial enrichment of the unusual sphingolipid dihydrosphingomyelin and a loss of viral infectivity upon inhibition of sphingolipid biosynthesis in host cells are reported, establishing a critical role for this lipid class in the HIV replication cycle. Intriguingly, the overall lipid composition of native HIV membranes resembles detergent-resistant membrane microdomains and is strikingly different from that of host cell membranes. With this composition, the HIV lipidome provides strong evidence for the existence of lipid rafts in living cells.dihydrosphingomyelin ͉ nano-electrospray ionization tandem mass spectrometry ͉ lipid analysis ͉ viral membrane

Removal of envelope protein‐free retroviral vectors by anion‐exchange chromatography to improve product quality

“…On the other hand Env -vectors have an exposed lipid bilayer with a composition distinct from the cell membrane due to budding of the RVs from lipid rafts enriched in cholesterol and sphingomyelin [32,33]. The viral lipid bilayer is composed by 27 -30% phosphatidylcholine, 25 -27% phosphatidylethanolamine, 1 -2% phosphatidylinositol, PS 12 -16% phosphatidylserine, 1 -2% phosphatidic acid, and 22 -25% sphingomyelin [34].…”

“…The viral lipid bilayer is composed by 27 -30% phosphatidylcholine, 25 -27% phosphatidylethanolamine, 1 -2% phosphatidylinositol, PS 12 -16% phosphatidylserine, 1 -2% phosphatidic acid, and 22 -25% sphingomyelin [34]. The overall lipid composition points to an excess of negative charges at pH above 4 [35]; however, it is known that the distribution of the lipids in the membrane is asymmetric with the neutral species (phosphatidylcholine and sphingomyelin) and cholesterol located mostly in the outer leaflet and the negatively charged lipids (phosphatidylinositol, phosphatidic acid, and phosphatidylserine) together with zwiterionic phosphatidylethanolamine mostly located in the inner leaflet of the membrane [33]. Although the f-potential data indicates that the Env -vectors have an overall negative charge at physiological pH, the majority of the lipids at the surface of the retroviral are zwitterionic and intrinsically inert.…”

Lipidomics of host–pathogen interactions

“…Phosphatidylcholine accounts to 75% of total phospholipid [85] GP Viral envelopes are enriched in sphingomyelin [8,86] SP Envelope cholesterol is critical for structure and infectivity [87][88][89] ST 2 Phosphatidylserine stimulates entry of enveloped viruses [90,91] Mannose receptor binds to the ManLAM mannose caps of mycobacteria and mediates phagocytosis [92] GPI anchored proteins (host [35,36] and parasite [37] …”

“…Unsaturated fatty acids block HIV budding [126] Mycobactin mediates iron supply within macrophages [32] FA Affinity of HIV Gag protein is regulated by myristoyl switch [127] Presentation of glycerophospholipids, sulfolipids and mycolates via CD1 receptors [58,132,133] GP Golgi-derived viruses have different phospholipid (incl semilysobisphosphatidic acid) composition depending on the precise site of budding [7,128] HIV-like particle assembly is regulated by inositol phosphates [129] HIV-1 Gag targeting is regulated by PIP2 [130] Vaccinia virus envelope protein p37 has lipase activity [131] Nef transports cholesterol to site of HIV budding [134] ST Budding occurs from glycolipid-enriched membrane lipid rafts [8,[135][136][137] Table summarizing the reported involvement of lipids, both from the host as well as the pathogen, during various stages of host-pathogen interaction ( Fig. 1).…”

“…lysobisphosphatidic acids) [7]. Cell surface packaged viruses (such as HIV in most cases) are rich in cholesterol and sphingolipids [8]. This has implications for the properties of the envelope membrane.…”