Role for Influenza Virus Envelope Cholesterol in Virus Entry and Infection

Sun, Xiangjie; Whittaker, Gary R.

doi:10.1128/jvi.77.23.12543-12551.2003

Cited by 198 publications

(214 citation statements)

References 50 publications

(58 reference statements)

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“…Influenza virus envelope cholesterol also plays a role in virus entry and infection 40 . It has been hypothesized that influenza hemagglutinin concentrates by partitioning into lipid raft microdomains, thus reaching densities needed for the hemagglutinin-mediated fusion of virus infection 41 .…”

Section: Discussionmentioning

confidence: 99%

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Polozov¹,

Bezrukov²,

Gawrisch³

et al. 2008

Nat Chem Biol

208

159

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Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 1C ordered and disordered lipid domains coexisted for the viral envelope and extracts thereof. At 22 1C much lipid was in a gel phase, the fraction of which reversibly increased with cholesterol depletion. Diffusion measurements and fluorescence microscopy independently confirmed the existence of gel-phase domains. Thus the existence of ordered regions of lipids in biological membranes is now demonstrated. Above the physiological temperatures of influenza infection, the physical properties of viral envelope lipids, regardless of protein content, were indistinguishable from those of the disordered fraction. Viral fusion appears to be uncorrelated to ordered lipid content. Lipid ordering may contribute to viral stability at lower temperatures, which has recently been found to be critical for airborne transmission.Membranes of most enveloped viruses form by budding out from the plasma membranes of their host cells a highly select subset of plasma membrane components. In general, the selected membrane proteins are coded by the viral genome, whereas lipids are recruited from host membranes; however, the lipid composition of the viral envelope differs from that of the host membrane 1,2 and from other budding viruses 3 . The envelope of influenza contains higher amounts of both cholesterol 1 and glycosphingolipids 4 -lipids known to partition into the liquid ordered (l o ) phase. The l o phase is characterized by extended hydrocarbon chains having a reduced gauche-trans isomerization compared with those of the liquid disordered (l d ) phase, but having a similar rotational and translational mobility 5 . Liquid ordered phases are thought to be at the core of lipid rafts 6 , which are defined as transient membrane microdomains that are enriched in sphingolipids and cholesterol (1) 7 -a hypothesis that has generated much debate 8,9 .The influenza virus has played a pivotal role in the development of the raft hypothesis, starting with early studies that inferred ordered domains using spin probes 10-12 and fluorescence 13,14 and that suggested that an ordered lipid domain is selected in toto as the envelope during budding from the plasma membrane 15 . These lipids are either selected at the time of budding or pre-selected as the 'pre-envelope' suggested by clusters of the viral envelope protein hemagglutinin seen in immunoelectron microscopy 16 .Although detection of virus-sized domains of lipids (B100-nm diameter) is below the limit of resolution of fluorescent microscopy, large micrometer-sized membrane domains are reliably detected [17][18][19] . Recently, proton magic angle spinning NMR ( 1 H MAS NMR) has been used to determine the phase diagram of the same lipid compositions used to study large membrane domains in lipid bilayers and othe...

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Section: Discussionmentioning

confidence: 99%

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Polozov¹,

Bezrukov²,

Gawrisch³

et al. 2008

Nat Chem Biol

208

159

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Section: Lipid Microdomains and Membrane Raftsmentioning

confidence: 99%

“…Many papers suggested that lipid rafts were involved in various cellular processes such as signal transduction, apoptosis or protein sorting [20,21]. They have also been shown to play a role in HIV or influenza viruses infection processes [22][23][24].Model membrane experiments have shown that liquidordered microdomains in fluid membranes can exist and that proteins can preferentially segregate into the fluid or the ordered phase domain [25,26]. However, biological membranes are much more complex than synthetic membranes, and the presence of lipid rafts in intact cells still remains to be proved.…”

mentioning

confidence: 99%

What do diffusion measurements tell us about membrane compartmentalisation? Emergence of the role of interprotein interactions

2008

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The techniques of diffusion analysis based on optical microscopy approaches have revealed a great diversity of the dynamic organisation of cell membranes. For a long period, two frameworks have dominated the way of representing the membrane structure: the membrane skeleton fences and the lipid raft models. Progresses in the methods of data analysis have shed light on the features and consequently the possible origin of membrane domains: Inter-protein interactions play a role in confinement. Innovative developments pushing forward the spatiotemporal resolution limits are currently emerging, which are likely to provide in the future a detailed understanding of the intimate functional dynamic organisation of the cell membrane. Keywords Membrane domain . Diffusion . Protein interaction OverviewThe main function of membranes is to generate close compartments: The cell itself (by the plasma membrane) and also the nucleus (by nuclear envelope), the Golgi apparatus, the endoplasmic reticulum, various organelles or the vesicles which are involved in transport processes. Membranes delimit these structures and allow them to have a different composition from the rest of the cell by restricting the diffusion of ions and macromolecules. The specific transport of molecules or information across the membrane is devoted to membrane proteins. Membranes are essentially composed of lipid and proteins, each of them representing about 50% in weight. Lipids are amphiphilic molecules that spontaneously form a bilayer in water. Among the variety of lipids, cholesterol has a specific place since it is particularly abundant in eukaryotic cells. Cholesterol can modify the lipid molecular order [1] and is presumed to participate in lipid micro-phase separation (rafts) [2][3][4][5].Since the structure of biological membranes is maintained by non-covalent bonds, they have first been considered as a fluid lipid bilayer in which embedded proteins are free to diffuse [6]. After the advent of this fluid mosaic model postulating a random distribution of membrane molecules [6], experimental evidence showed that the proteins and lipids are distributed heterogeneously in the membrane. For example, incomplete recoveries were systematically observed in fluorescence recovery after photobleaching (FRAP; see "Appendix 1") experiments. The first indication of the presence of micrometer-sized domains was obtained by FRAP. Yechiel and Edidin found a decrease of the mobile fraction with increasing radius of the bleaching spot ([7, 8] and see "Appendix 1").The huge diversity of lipids and proteins implies that a very large number of combinatorial interactions can occur between them [9]. Since all lipids and proteins do not J Chem Biol (2008) [14,15]. Interactions of membrane proteins with the cytoskeleton or with the glycocalyx can also affect the membrane organisation and are likely to play a confining role [16]. A significant challenge of cell biology is to characterise and to understand not only the origin but also the role of these micrometric ...

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“…As commented before, specific lipids located in the viral particles can also play a role on viral entry of enveloped viruses [8], including 'those located in' lipid rafts [49][50][51]. Vaccinia virus provides another example of the relationships between lipids located on the viral particle and viral entry.…”

Section: Lipids and Viral Internalizationmentioning

confidence: 99%

“…Lipid rafts have been related to the entry of a number of viruses, for example the coronavirus severe acute respiratory syndrome (SARS), murine leukemia virus, herpes simplex virus, Japanese encephalitis virus, SV40, and echovirus 1 [34,[43][44][45][46][47][48]. In addition, some viruses require cholesterol-enriched microdomains in the viral membrane for efficient virus entry, for example influenza virus A, human herpes virus 6, and Canine distemper virus [49][50][51]. On the other hand, some viruses that enter into the cells using mechanisms independent of lipid rafts require cholesterol for an efficient internalization.…”

Section: Lipids and Viral Internalizationmentioning

confidence: 99%

Lipid Involvement in Viral Infections: Present and Future Perspectives for the Design of Antiviral Strategies

Martín-Acebes¹,

Vázquez-Calvo²,

Caridi³

et al. 2013

Lipid Metabolism

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Role for Influenza Virus Envelope Cholesterol in Virus Entry and Infection

Cited by 198 publications

References 50 publications

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

Progressive ordering with decreasing temperature of the phospholipids of influenza virus

What do diffusion measurements tell us about membrane compartmentalisation? Emergence of the role of interprotein interactions

Lipid Involvement in Viral Infections: Present and Future Perspectives for the Design of Antiviral Strategies

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