Lysolipids Do Not Inhibit Influenza Virus Fusion by Interaction with Hemagglutinin

Baljinnyam, Bolormaa; Schroth‐Diez, Britta; Korte, Thomas; Herrmann, Andreas

doi:10.1074/jbc.m112217200

Cited by 6 publications

(6 citation statements)

References 43 publications

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“…It is interesting that liposomes containing TPE (phospholipid inducing negative curvature) displayed relatively high hemifusion and fusion values, whereas liposomes containing LPC (phospholipid inducing positive curvature) were the ones that elicited the lowest values. This inhibitory effect produced by inverted-coneshaped phospholipids has been previously observed in some viral and nonviral fusion systems (67)(68)(69)(70). This effect could be due to the fact that E2 FP , located at the bilayer interface and interacting with the phospholipid headgroups, could be capable of changing the polymorphic phase behavior of the membrane bilayer, since it was able to inhibit the presence of hexagonal phases but induce the presence of other lamellar phases (isotropic 31 P-NMR signal, but lamellar SAXD diffraction pattern).…”

Section: Discussionsupporting

confidence: 63%

Interaction of the Most Membranotropic Region of the HCV E2 Envelope Glycoprotein with Membranes. Biophysical Characterization

Pérez-Berná

Guillén

Moreno

et al. 2008

Biophysical Journal

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The previously identified membrane-active regions of the hepatitis C virus (HCV) E1 and E2 envelope glycoproteins led us to identify different segments that might be implicated in viral membrane fusion, membrane interaction, and/or protein-protein binding. HCV E2 glycoprotein contains one of the most membranotropic segments, segment 603-634, which has been implicated in CD81 binding, E1/E2 and E2/E2 dimerization, and membrane interaction. Through a series of complementary experiments, we have carried out a study of the binding and interaction with the lipid bilayer of a peptide corresponding to segment 603-634, peptide E2(FP), as well as the structural changes induced by membrane binding that take place in both the peptide and the phospholipid molecules. Here, we demonstrate that peptide E2(FP) binds to and interacts with phospholipid model membranes, modulates the polymorphic phase behavior of membrane phospholipids, is localized in a shallow position in the membrane, and is probably oligomerized in the presence of membranes. These data support the role of E2(FP) in HCV-mediated membrane fusion, and sustain the notion that this segment of the E2 envelope glycoprotein, together with other segments of E2 and E1 glycoproteins, provides the driving force for the merging of the viral and target cell membranes.

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Section: Discussionsupporting

confidence: 63%

Interaction of the Most Membranotropic Region of the HCV E2 Envelope Glycoprotein with Membranes. Biophysical Characterization

Pérez-Berná

Guillén

Moreno

et al. 2008

Biophysical Journal

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“…Consistent with the requirement for strong bending of the outer membrane leaflets for stalk formation, our data have shown that incorporation of invertedcone-shaped lipids (positive curvature) such as LPC in this leaflet of the target membrane had a strong inhibitory effect on fusion, whereas it was slightly enhanced when cone-shaped lipids (negative curvature) were used. Similar inhibitory effects of inverted-cone-shaped lipids that could be related to membrane curvature effects have been observed in a number of viral and nonviral fusion systems, including influenza virus (3,9), baculovirus (7), human immunodeficiency virus (33), rabies virus (15), cortical granule exocytosis (50), and microsome fusion (10).…”

Section: Discussionmentioning

confidence: 95%

Effect of Membrane Curvature-Modifying Lipids on Membrane Fusion by Tick-Borne Encephalitis Virus

Stiasny

Heinz

2004

J Virol

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Enveloped viruses enter cells by fusion of their own membrane with a cellular membrane. Incorporation of inverted-cone-shaped lipids such as lysophosphatidylcholine (LPC) into the outer leaflet of target membranes has been shown previously to impair fusion mediated by class I viral fusion proteins, e.g., the influenza virus hemagglutinin. It has been suggested that these results provide evidence for the stalk-pore model of fusion, which involves a hemifusion intermediate (stalk) with highly bent outer membrane leaflets. Here, we investigated the effect of inverted-cone-shaped LPCs and the cone-shaped oleic acid (OA) on the membrane fusion activity of a virus with a class II fusion protein, the flavivirus tick-borne encephalitis virus (TBEV). This study included an analysis of lipid mixing, as well as of the steps preceding or accompanying fusion, i.e., binding to the target membrane and lipid-induced conformational changes in the fusion protein E. We show that the presence of LPC in the outer leaflet of target liposomes strongly inhibited TBEV-mediated fusion, whereas OA caused a very slight enhancement, consistent with a fusion mechanism involving a lipid stalk. However, LPC also impaired the low-pH-induced binding of a soluble form of the E protein to liposomes and its conversion into a trimeric postfusion structure that requires membrane binding at low pH. Because inhibition is already observed before the lipid-mixing step, it cannot be determined whether impairment of stalk formation is a contributing factor in the inhibition of fusion by LPC. These data emphasize, however, the importance of the composition of the target membrane in its interactions with the fusion peptide that are crucial for the initiation of fusion.Fusion of viral membranes with cellular membranes is a key step in the entry of enveloped viruses into cells. It requires energy to overcome repulsive forces between the opposing membranes and to locally disrupt the original lipid bilayer structures. This energy is provided by structural changes and protein-protein, as well as protein-lipid, interactions of specific viral envelope proteins, designated viral fusion proteins. In infectious virions these proteins exist in a metastable state and respond to a specific fusion trigger (receptor binding or acidic pH) by conformational changes that lead to the exposure of the fusion peptide and the formation of an energetically more stable postfusion structure (23,25,49). So far, two structurally different classes of viral fusion proteins have been identified (30). Class I is represented by the spike-like envelope proteins found in orthomyxo-, paramyxo-, retro-, filo-, and coronaviruses. They are characterized by amino-terminal or amino-proximal fusion peptides, as well as the formation of a hairpin-like postfusion structure with a central trimeric coiled coil. In this postfusion form the membraneinserted N and C termini are located at the same end of a very stable protein rod (11, 51). The class II fusion proteins of flaviviruses and alphaviruses are c...

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“…To study both processes, a significant number of different experimental models have been developed that are primarily based on viral binding studies to glycophorin or ganglioside containing liposomes. ,− In these models the fusion of two spherical objects, the virus and the liposome, is monitored but in situ target tissues are nonspherical and are formed by planar cellular monolayers of ganglioside exposing cells. However, there is also a significant number of studies that show that the lipid curvature of the liposome is a parameter that influences fusion efficiency of the influenza and other viruses. ,− Here we report a new experimental model that is based on the viral binding to planar, mica supported membranes containing gangliosides. The observations made on this system therefore does not depend on the intrinsic curvature of target membranes.…”

Section: Discussionmentioning

confidence: 99%

Mimicking Influenza Virus Fusion Using Supported Lipid Bilayers

et al. 2014

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Influenza virus infection is a serious public health problem in the world, and understanding the molecular mechanisms involved in viral replication is crucial. In this paper, we used a minimalist approach based on a lipid bilayer supported on mica, which we imaged by atomic force microscopy (AFM) in a physiological buffer, to analyze the different steps of influenza fusion, from the interaction of intact viruses with the supported bilayer to their complete fusion. Our results show that sialic acid recognition and priming upon acidification are sufficient for a complete fusion with the host cell membrane. After fusion, a flat and continuous membrane was observed. Because of the fragility of the viral membrane that was removed by the tip, most probably due to the disorganization of the matrix layer at acidic pH, fine structural details of ribonucleoproteins (RNP) were obtained. In addition, AFM topography of intact virus in interaction with the supported lipid bilayer confirms that hemeagglutinin and neuraminidase can form isolated clusters within the viral membrane.

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Lysolipids Do Not Inhibit Influenza Virus Fusion by Interaction with Hemagglutinin

Cited by 6 publications

References 43 publications

Interaction of the Most Membranotropic Region of the HCV E2 Envelope Glycoprotein with Membranes. Biophysical Characterization

Interaction of the Most Membranotropic Region of the HCV E2 Envelope Glycoprotein with Membranes. Biophysical Characterization

Effect of Membrane Curvature-Modifying Lipids on Membrane Fusion by Tick-Borne Encephalitis Virus

Mimicking Influenza Virus Fusion Using Supported Lipid Bilayers

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