Low pH induced membrane fusion of lipid vesicles containing proton-sensitive polymer

Biochemistry ◽  
1987 ◽  
Vol 26 (25) ◽  
pp. 8145-8150 ◽  
Author(s):  
Naoto Oku ◽  
Sayumi Shibamoto ◽  
Fumiaki Ito ◽  
Hisanori Gondo ◽  
Mamoru Nango
Keyword(s):  
Membrane Fusion ◽  
Lipid Vesicles ◽  
Low Ph ◽  
Induced Membrane

scholarly journals A Functional F Analogue of Autographa californica Nucleopolyhedrovirus GP64 from the Agrotis segetum Granulovirus

2008 ◽  
Vol 82 (17) ◽  
pp. 8922-8926 ◽  
Author(s):  
Feifei Yin ◽  
Manli Wang ◽  
Ying Tan ◽  
Fei Deng ◽  
Just M. Vlak ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Plutella Xylostella ◽  
Syncytium Formation ◽  
Low Ph ◽  
Autographa Californica ◽  
Agrotis Segetum ◽  
Induced Membrane ◽  
F Protein ◽  
Autographa Californica Nucleopolyhedrovirus

ABSTRACT The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping system. In the present study the F protein of Agrotis segetum GV (AgseGV) was identified experimentally as the first functional GP64 analogue from GVs. AgseF can rescue virion propagation and infectivity of gp64-null AcMNPV. The AgseF-pseudotyped AcMNPV also induced syncytium formation as a consequence of low-pH-induced membrane fusion.

Deacylation of influenza virus hemagglutinin does not affect the kinetics of low pH induced membrane fusion

1996 ◽  
Vol 431 (S6) ◽  
pp. R257-R258 ◽  
Author(s):  
Britta Schroth ◽  
Hans C. Philipp ◽  
Michael Veit ◽  
Michael F. G. Schmidt ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Low Ph ◽  
Induced Membrane ◽  
Influenza Virus Hemagglutinin ◽  
Kinetics Of

scholarly journals Second-Site Revertants of a Semliki Forest Virus Fusion-Block Mutation Reveal the Dynamics of a Class II Membrane Fusion Protein

2006 ◽  
Vol 80 (12) ◽  
pp. 6115-6122 ◽  
Author(s):  
Chantal Chanel-Vos ◽  
Margaret Kielian
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Semliki Forest Virus ◽  
Protein A ◽  
Class Ii ◽  
Low Ph ◽  
Induced Membrane ◽  
Membrane Fusion Protein ◽  
E1 Protein ◽  
Fusion Loop

ABSTRACT The alphavirus Semliki Forest virus (SFV) infects cells through low-pH-induced membrane fusion mediated by the E1 protein, a class II virus membrane fusion protein. During fusion, E1 inserts into target membranes via its hydrophobic fusion loop and refolds to form a stable E1 homotrimer. Mutation of a highly conserved histidine (the H230A mutation) within a loop adjacent to the fusion loop was previously shown to block SFV fusion and infection, although the mutant E1 protein still inserts into target membranes and forms a homotrimer. Here we report on second-site mutations in E1 that rescue the H230A mutant. These mutations were located in a cluster within the hinge region, at the membrane-interacting tip, and within the groove where the E1 stem is believed to pack. Together the revertants reveal specific and interconnected aspects of the fusion protein refolding reaction.

scholarly journals Interactions of Semliki Forest virus spike glycoprotein rosettes and vesicles with cultured cells.

1983 ◽  
Vol 96 (2) ◽  
pp. 455-461 ◽  
Author(s):  
M Marsh ◽  
E Bolzau ◽  
J White ◽  
A Helenius
Keyword(s):  
Cell Surface ◽  
Membrane Fusion ◽  
Semliki Forest Virus ◽  
Lipid Vesicles ◽  
Low Ph ◽  
Fusion Activity ◽  
Spike Glycoprotein ◽  
Surface Binding ◽  
Coated Pits ◽  
Intact Virus

Semliki Forest virus (SFV)-derived spike glycoprotein rosettes (soluble octameric complexes), virosomes (lipid vesicles with viral spike glycoproteins), and liposomes (protein-free lipid vesicles) have been used to investigate the interaction of subviral particles with BHK-21 cells. Cell surface binding, internalization, degradation, and low pH-dependent membrane fusion were quantitatively determined. Electron microscopy was used to visualize the interactions. Virosomes and rosettes, but not liposomes, bound to cells. Binding occurred preferentially to microvilli and was inhibited by added SFV; it increased with decreasing pH but was, in all cases, less efficient than intact virus. At 37 degrees C the cell surface-bound rosettes and virosomes were internalized via coated pits and coated vesicles. After a lag period of 45 min the protein components of the internalized ligands were degraded and appeared, as acid-soluble activity, in the medium. The uptake of rosettes and virosomes was found to be similar to the adsorptive endocytosis of SFV except that their average residence times on the cell surface were longer. The rosettes and the liposomes did not show low pH-induced membrane fusion activity. The virosomes, however, irrespective of the lipid compositions used, displayed hemolytic activity at mildly acidic pH and were able to fuse with the plasma membrane of cells with an efficiency of 0.25 that observed with intact viruses. Cell-cell fusion activity was not observed with any of the subviral components. The results indicated that subviral components possess some of the entry properties of the intact virus.

scholarly journals Low-pH-Induced Membrane Fusion Mediated by Human Metapneumovirus F Protein Is a Rare, Strain-Dependent Phenomenon

2008 ◽  
Vol 82 (17) ◽  
pp. 8891-8895 ◽  
Author(s):  
Sander Herfst ◽  
Vicente Mas ◽  
Lorena S. Ver ◽  
Rutger J. Wierda ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Low Ph ◽  
Human Metapneumovirus ◽  
Acidic Ph ◽  
Induced Membrane ◽  
F Protein ◽  
Genetic Lineages ◽  
Ph Dependent ◽  
Strain Dependent

ABSTRACT Membrane fusion promoted by human metapneumovirus (HMPV) fusion (F) protein was suggested to require low pH (R. M. Schowalter, S. E. Smith, and R. E. Dutch, J. Virol. 80:10931-10941, 2006). Using prototype F proteins representing the four HMPV genetic lineages, we detected low-pH-dependent fusion only with some lineage A proteins and not with lineage B proteins. A glycine at position 294 was found responsible for the low-pH requirement in lineage A proteins. Only 6% of all HMPV lineage A F sequences have 294G, and none of the lineage B sequences have 294G. Thus, acidic pH is not a general trigger of HMPV F proteins for activity.

scholarly journals Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation

2004 ◽  
Vol 23 (4) ◽  
pp. 728-738 ◽  
Author(s):  
Stéphane Bressanelli ◽  
Karin Stiasny ◽  
Steven L Allison ◽  
Enrico A Stura ◽  
Stéphane Duquerroy ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Envelope Glycoprotein ◽  
Low Ph ◽  
Induced Membrane

scholarly journals Screening and Identification of Lassa Virus Entry Inhibitors from an FDA-Approved Drug Library

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Peilin Wang ◽  
Yang Liu ◽  
Guangshun Zhang ◽  
Shaobo Wang ◽  
Jiao Guo ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Virus Entry ◽  
Low Ph ◽  
Mechanistic Study ◽  
Lassa Virus ◽  
Content Type ◽  
Induced Membrane ◽  
Entry Inhibitors ◽  
Pseudotype Virus ◽  
Approved Drugs

ABSTRACT Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. At present, there are no Food and Drug Administration (FDA)-approved drugs or vaccines specific for LASV. Here, high-throughput screening of an FDA-approved drug library was performed against LASV entry by using pseudotype virus bearing LASV envelope glycoprotein (GPC). Two hit compounds, lacidipine and phenothrin, were identified as LASV entry inhibitors in the micromolar range. A mechanistic study revealed that both compounds inhibited LASV entry by blocking low-pH-induced membrane fusion. Accordingly, lacidipine showed virucidal effects on the pseudotype virus of LASV. Adaptive mutant analyses demonstrated that replacement of T40, located in the ectodomain of the stable-signal peptide (SSP), with lysine (K) conferred LASV resistance to lacidipine. Furthermore, lacidipine showed antiviral activity against LASV, the closely related Mopeia virus (MOPV), and the New World arenavirus Guanarito virus (GTOV). Drug-resistant variants indicated that V36M in the ectodomain of the SSP mutant and V436A in the transmembrane domain of the GP2 mutant conferred GTOV resistance to lacidipine, suggesting the interface between SSP and GP2 is the target of lacidipine. This study shows that lacidipine is a candidate for LASV therapy, reinforcing the notion that the SSP-GP2 interface provides an entry-targeted platform for arenavirus inhibitor design. IMPORTANCE Currently, there is no approved therapy to treat Lassa fever; therefore, repurposing of approved drugs will accelerate the development of a therapeutic stratagem. In this study, we screened an FDA-approved library of drugs and identified two compounds, lacidipine and phenothrin, which inhibited Lassa virus entry by blocking low-pH-induced membrane fusion. Additionally, both compounds extended their inhibition against the entry of Guanarito virus, and the viral targets were identified as the SSP-GP2 interface.

Sign in / Sign up

Export Citation Format

Share Document