Low pH-induced pore formation by spike proteins of enveloped viruses

Käsermann, Fabian; Kempf, Christoph

doi:10.1099/0022-1317-77-12-3025

Cited by 19 publications

(20 citation statements)

References 34 publications

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“…VSV faces the same intriguing question about what is responsible for the dissociation of M protein from RNPs. Unlike influenza virus, VSV lacks an ion channel protein although previous studies have found at low pH spike proteins of enveloped viruses such as VSV, Sindbis virus, and Semliki Forest virus can make the viral envelope permeable to propidium iodide (101,114). Also, cells expressing these proteins on the cell surface show a pH-dependent permeability (101,114).…”

Section: Vsv Entry and Uncoatingmentioning

confidence: 98%

“…This was an interesting result since influenza virus uses the M2 ion channel protein for acidification of the virion interior (110,169) and our results suggested that VSV uses a different method to accomplish a similar feat with its G protein. Previous studies have found spike proteins of several different enveloped viruses including VSV, Sindbis Virus (SIN), Semliki Forest virus (SFV), influenza HA, and Ebola virus GP2 when exposed to acidic pH, can increase membrane permeability when cells expressing these proteins on the cell surface are exposed to low pH (76,101,112,182). The SFV spike protein's involvement in membrane disruption at low pH was extensively studied with cell permeabilization assays, whole-cell patch-clamp recordings, and dual voltage-clamp intracellular current flow monitoring (112,113,115) and was predicted to be due to pore formation by the E 1 -E 2 -E 3 protein trimers that make up the SFV spike (114).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike influenza virus, VSV lacks an ion channel protein although previous studies have found at low pH spike proteins of enveloped viruses such as VSV, Sindbis virus, and Semliki Forest virus can make the viral envelope permeable to propidium iodide (101,114). Also, cells expressing these proteins on the cell surface show a pH-dependent permeability (101,114). These observations coupled with the knowledge of how influenza virus uncoats would lead one to believe that protons may be able to cross the viral envelope and affect M in a manner similar to M1.…”

Section: Vsv Entry and Uncoatingmentioning

confidence: 99%

“…Acidification of the virus interior decreases the interaction between M1 and nucleocapsids allowing for their dissociation before entry of the nucleocapsids into the cytoplasm (222). VSV lacks a similar proton channel, though previous studies have found that spike proteins of enveloped viruses such as VSV, Sindbis virus, and Semliki Forest virus and Ebola virus GP2 can increase membrane permeability (76,101,112). Though not studied in the context of virus it has been suggested that the haemaglutinin (HA) protein of Influenza at the pH required for fusion can also cause cell permeability and proton influx when found on the cell membrane (182).…”

Section: Chapter 3: Low Ph Enhancement Of Matrix Uncoating Introductionmentioning

confidence: 99%

“…We found that the effect of pH on the MLumio-Green fluorescence within intact virus was G-dependent and further biochemical analysis indicated that low pH resulted in an enhancement of M dissociation from partially permeabilized but intact virions. We propose a model for the initial uncoating events of VSV based on our observations and past viral spike protein membrane disruption studies (76,101,112,182).…”

Section: Chapter 3: Low Ph Enhancement Of Matrix Uncoating Introductionmentioning

confidence: 99%

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Investigation of the Vesicular Stomatitis Virus Matrix Protein: Uncoating and Assembly

Mire¹

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Section: Vsv Entry and Uncoatingmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Vsv Entry and Uncoatingmentioning

confidence: 99%

Section: Chapter 3: Low Ph Enhancement Of Matrix Uncoating Introductionmentioning

confidence: 99%

Section: Chapter 3: Low Ph Enhancement Of Matrix Uncoating Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Investigation of the Vesicular Stomatitis Virus Matrix Protein: Uncoating and Assembly

Mire¹

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Individual Expression of Sindbis Virus Glycoproteins. E1 Alone Promotes Cell Fusion

2003

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The envelope of alphavirus particles contains two major glycoproteins, E1 and E2, that participate in virus entry and assembly of new virus particles. Interactions between these glycoproteins determine their correct functioning. The expression of each glycoprotein in the absence of the other counterpart was achieved by means of electroporation of modified Sindbis virus (SV) genomes. In addition, in trans coexpression of both glycoproteins was also tested in BHK cells. Synthesis of the E1 glycoprotein alone gave rise to cell fusion after incubation in low-pH medium. In addition, expression of E1 in the absence of the E2 precursor, PE2 (E3+E2), induced the formation of cytoplasmic vacuoles in the transfected cells. The normal phenotype was recovered when PE2 was coexpressed in trans with E1. Moreover, this coexpression modified the processing of the PE2 glycoprotein. PE2 synthesized in the absence of E1 gave rise to a product, E2', whose migration was slower in SDS-polyacrylamide gel than that of genuine E2 from SV-infected cells. This alteration was corrected upon in trans coexpression of E1 and PE2. These results suggest that the two glycoproteins, E1 and PE2, interact after their expression from two separate SV genomes. Notably, BHK cells cotransfected with the two modified genomes produced SV particles. Our findings suggest that SV E1 and E2 synthesized in trans can interact with each other and participate together with capsid protein in the assembly of new virus particles.

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The regulation of disassembly of alphavirus cores

Wengler

2009

Arch Virol

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Alphaviruses are used as model viruses for structure determination and for analysis of virus entry. They are used also as vectors for protein expression and gene therapy. Virus particles are assembled by budding, using preformed cores and a modified cellular membrane. During entry, alphaviruses release the viral core into the cytoplasm. Cores are disassembled during virus entry and accumulate in the cytoplasm during virus multiplication. The regulation of core disassembly is the subject of this review. A working model compatible with all experimental data is formulated. This model comprises the following steps: (1) The incoming core is present in the cytoplasm in a metastable state, primed for disassembly. A core structure containing the so-called linker region of the core protein in an exposed position susceptible to proteolytic cleavage on the core surface might represent the primed state. (2) The primed core allows access of cellular proteins to the viral genome RNA, e.g. initiation factors of protein synthesis. (3) In a following step, ribosomal 60S subunits bind to the complex and lead to core disassembly with a concomitant transfer of core protein or of core protein fragments to the 28S rRNA. The linker region may be involved in this transfer. (4) During the later stages of virus multiplication, cellular components involved in step (2) and/or in step (3) are inactivated. This inactivation might involve the binding of newly synthesised core protein to 28S rRNA. (5) Unprimed cores, e.g. core particles containing the linker region in an unexposed position, are assembled during virus multiplication. Priming of cores and inactivation of host-cell factors each represent a complete mechanism of regulation of core disassembly. Future experiments will show whether or not both processes are actually used. Since alphaviruses, e.g. Chikungunya virus, Ross River virus, Semliki Forest virus, and Sindbis virus, are human pathogens, these experiments are of practical relevance, since they might identify targets for antiviral chemotherapy.

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Low pH-induced pore formation by spike proteins of enveloped viruses

Abstract: Exposure of Aedes albopictus cells infected with Semliki Forest virus (SFV;Togaviridae

Cited by 19 publications

References 34 publications

Investigation of the Vesicular Stomatitis Virus Matrix Protein: Uncoating and Assembly

Investigation of the Vesicular Stomatitis Virus Matrix Protein: Uncoating and Assembly

Individual Expression of Sindbis Virus Glycoproteins. E1 Alone Promotes Cell Fusion

The regulation of disassembly of alphavirus cores

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