The membrane proteins of flaviviruses form ion-permeable pores in the target membrane after fusion: identification of the pores and analysis of their possible role in virus infection

Koschinski, Andreas; Wengler, Gerd; Repp, Holger

doi:10.1099/vir.0.19062-0

Cited by 32 publications

(22 citation statements)

References 35 publications

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“…The low rate of entry seen at nonphysiological cold temperatures may reflect the impairment of cellular functions that may be required to favor the genome delivery process. Supporting this model of infection is the observation that alphavirus entry into living cells is a leaky process (33)(34)(35), allowing the passage of small molecules and ions through the plasma membrane. In contrast, virus-liposome membrane fusion has been shown to be a nonleaky process (36).…”

Section: Discussionmentioning

confidence: 99%

Alphavirus Genome Delivery Occurs Directly at the Plasma Membrane in a Time- and Temperature-Dependent Process

Vancini

Wang

Ferreira

et al. 2013

J Virol

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It is widely held that arboviruses such as the alphavirus Sindbis virus gain entry into cells by a process of receptor-mediated endocytosis followed by membrane fusion in the acid environment of the endosome. We have used an approach of direct observation of Sindbis virus entry into cells by electron microscopy and immunolabeling of virus proteins with antibodies conjugated to gold beads. We found that upon attaching to the cell surface, intact RNA-containing viruses became empty shells that could be identified only by antibody labeling. We found that the rate at which full particles were converted to empty particles increased with time and temperature. We found that this entry event takes place at temperatures that inhibit both endosome formation and membrane fusion. We conclude that entry of alphaviruses is by direct penetration of cell plasma membranes through a pore structure formed by virus and, possibly, host proteins.

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Section: Discussionmentioning

confidence: 99%

Alphavirus Genome Delivery Occurs Directly at the Plasma Membrane in a Time- and Temperature-Dependent Process

Vancini

Wang

Ferreira

et al. 2013

J Virol

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“…However, these eVects are much less pronounced than for Alphaviruses with respect to the overall fusion and can only be demonstrated when fusion is slowed down by lowering the temperature (Stiasny et al 2003). Recent data suggested that Flaviviruses could enter their host cells by fusing with the plasma membrane at neutral pH, due to an interaction with a membrane patch of appropriate lipid composition (Koschinski et al 2003). However, increasing in vivo evidence indicates that most Flaviviridae enter their host cells by endocytosis after receptor recognition at the plasma membrane (Stiasny and Heinz 2006).…”

Section: Speciwc Interactions Between Viral Envelope Glycoproteins Anmentioning

confidence: 99%

Lipids as modulators of membrane fusion mediated by viral fusion proteins

2007

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Enveloped viruses infect host cells by fusion of viral and target membranes. This fusion event is triggered by specific glycoproteins in the viral envelope. Fusion glycoproteins belong to either class I, class II or the newly described third class, depending upon their arrangement at the surface of the virion, their tri-dimensional structure and the location within the protein of a short stretch of hydrophobic amino acids called the fusion peptide, which is able to induce the initial lipid destabilization at the onset of fusion. Viral fusion occurs either with the plasma membrane for pH-independent viruses, or with the endosomal membranes for pH-dependent viruses. Although, viral fusion proteins are parted in three classes and the subcellular localization of fusion might vary, these proteins have to act, in common, on lipid assemblies. Lipids contribute to fusion through their physical, mechanical and/or chemical properties. Lipids can thus play a role as chemically defined entities, or through their preferential partitioning into membrane microdomains called "rafts", or by modulating the curvature of the membranes involved in the fusion process. The purpose of this review is to make a state of the art on recent findings on the contribution of cholesterol, sphingolipids and glycolipids in cell entry and membrane fusion of a number of viral families, whose members bear either class I or class II fusion proteins, or fusion proteins of the recently discovered third class.

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“…We have previously shown that lanthanide ions block the ion pores generated during entry of alphaviruses at the plasma membrane without interfering with productive infection (Koschinski et al , 2005). As similar ion-permeable pores are generated during entry of the flavivirus West Nile virus (WNV) (Koschinski et al , 2003), we analysed the effect of lanthanide ions on the establishment of a productive infection by flaviviruses. The results of these studies are reported in this paper.…”

Section: Introductionmentioning

confidence: 99%

A short treatment of cells with the lanthanide ions La3+, Ce3+, Pr3+ or Nd3+ changes the cellular chemistry into a state in which RNA replication of flaviviruses is specifically blocked without interference with host-cell multiplication

Wengler

Koschinski

2007

Journal of General Virology

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Alpha- and flaviviruses contain class II fusion proteins, which form ion-permeable pores in the target membrane during virus entry. The pores generated during entry of the alphavirus Semliki Forest virus have been shown previously to be blocked by lanthanide ions. Here, analyses of the influence of rare earth ions on the entry of the flaviviruses West Nile virus and Uganda S virus revealed an unexpected effect of lanthanide ions. The results showed that a 30 s treatment of cells with an appropriate lanthanide ion changed the cellular chemistry into a state in which the cells no longer supported the multiplication of flaviviruses. This change occurred in cells treated before, during or after infection, did not inhibit multiplication of Semliki Forest virus and did not interfere with host-cell multiplication. The change was generated in vertebrate and insect cells, and was elicited in the presence of actinomycin D. In vertebrate cells, the change was elicited specifically by La3+, Ce3+, Pr3+ and Nd3+. In insect cells, additional lanthanide ions had this activity. Further analyses showed that lanthanide ion treatment blocked the ability of the host cell to support the replication of flavivirus RNA. These results open two areas of research: the study of molecular alterations induced by lanthanide ion treatment in uninfected cells and the analysis of the resulting modifications of the flavivirus RNA replicase complex. The findings possibly open the way for the development of a general chemotherapy against flavivirus diseases such as Dengue fever, Japanese encephalitis, West Nile fever and yellow fever.

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The membrane proteins of flaviviruses form ion-permeable pores in the target membrane after fusion: identification of the pores and analysis of their possible role in virus infection

Cited by 32 publications

References 35 publications

Alphavirus Genome Delivery Occurs Directly at the Plasma Membrane in a Time- and Temperature-Dependent Process

Alphavirus Genome Delivery Occurs Directly at the Plasma Membrane in a Time- and Temperature-Dependent Process

Lipids as modulators of membrane fusion mediated by viral fusion proteins

A short treatment of cells with the lanthanide ions La3+, Ce3+, Pr3+ or Nd3+ changes the cellular chemistry into a state in which RNA replication of flaviviruses is specifically blocked without interference with host-cell multiplication

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