Plasma Membrane-porating Domain in Poliovirus 2B Protein. A Short Peptide Mimics Viroporin Activity

Madan, Vanesa; Sánchez-Martínez, Silvia; Vedovato, Natascia; Rispoli, Giorgio; Carrasco, Luís; Nieva, José L.

doi:10.1016/j.jmb.2007.09.058

Cited by 37 publications

(45 citation statements)

References 75 publications

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“…3B). The permeabilization induced by an overlapping peptide library that spanned the complete viroporin 2B sequence mapped the cell plasma membrane-porating activity to the partially amphipathic HR1 domain (32). This region contains three lysine residues that would preclude TM disposition (Fig.…”

Section: Resultsmentioning

confidence: 99%

Membrane Integration of Poliovirus 2B Viroporin

Martínez-Gil

Bañó‐Polo

Redondo

et al. 2011

J Virol

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Virus infections can result in a variety of cellular injuries, and these often involve the permeabilization of host membranes by viral proteins of the viroporin family. Prototypical viroporin 2B is responsible for the alterations in host cell membrane permeability that take place in enterovirus-infected cells. 2B protein can be localized at the endoplasmic reticulum (ER) and the Golgi complex, inducing membrane remodeling and the blockade of glycoprotein trafficking. These findings suggest that 2B has the potential to integrate into the ER membrane, but specific information regarding its biogenesis and mechanism of membrane insertion is lacking. Here, we report experimental results of in vitro translation-glycosylation compatible with the transloconmediated insertion of the 2B product into the ER membrane as a double-spanning integral membrane protein with an N-/C-terminal cytoplasmic orientation. A similar topology was found when 2B was synthesized in cultured cells. In addition, the in vitro translation of several truncated versions of the 2B protein suggests that the two hydrophobic regions cooperate to insert into the ER-derived microsomal membranes.Virus infections can lead to a variety of cellular injuries, and usually these involve the restructuring of host membrane systems. Viroporins are a group of small virally encoded proteins that interact with cellular membranes to modify permeability and promote the release of viral particles. A typical feature exhibited by viroporins is the presence of at least one membrane-spanning helix anchoring the protein into membranes. After membrane insertion, their oligomerization creates hydrophilic channels or pores (22).Poliovirus is the enterovirus prototype member of the Picornaviridae family. This small, nonenveloped, icosahedral virus possesses a single-stranded 7.5-kb positive-sense RNA genome that encodes a single polyprotein. Polyprotein processing by virus-encoded proteases yields the structural P1 region proteins that encapsidate viral RNA and the nonstructural P2 and P3 region proteins involved in the replication of the viral RNA and membrane permeabilization (2). Nonstructural 2B protein is one of the products generated on processing the P2 region (62). Viroporin 2B has been identified as one of the viral proteins responsible for the alterations in host cell membrane permeability that take place in enterovirus-infected cells. Different 2B proteins expressed in cells have been localized at the endoplasmic reticulum (ER), Golgi complex, and, to a lesser extent, to the plasma and mitochondrial membranes (18,31,49,58). Biochemical and structural data indicate that viroporins form homo-oligomers that create pores in the ER and Golgi complex membranes (1,16,17,30,59). However, experimental data dealing with the mechanism of the membrane integration of the 2B product are lacking to date.The poliovirus 2B viroporin protein is hydrophobic overall and rather small (97 amino acids). Hydrophobicity within the viroporin 2B sequence seems to cluster in two main regions (F...

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Section: Resultsmentioning

confidence: 99%

Membrane Integration of Poliovirus 2B Viroporin

Martínez-Gil

Bañó‐Polo

Redondo

et al. 2011

J Virol

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“…The functions of the PV nonstructural proteins on host cells have been investigated by transfection of each protein individually and in combination. These experiments indicate that PV 2C and 2BC induce the formation of smooth membrane vesicles (11) and that 2B induces disassembly of the Golgi apparatus (64) and causes plasma membrane permeabilization (1,19,41,46). PV 3A slows protein movement through the secretory pathway (12,18,19) and causes swelling of ER membranes (18).…”

Section: Fmdv Infection Of Bhk Cells With Fmdv Causes Dramatic Changmentioning

confidence: 99%

Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3C ^pro

Armer

Moffat

Wileman

et al. 2008

J Virol

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Foot-and-mouth disease virus (FMDV), a member of theInfection of cells with most picornaviruses leads to a cytopathic effect (CPE) characterized by dramatic changes in cell shape and the production of large numbers of membrane vesicles within the cytoplasm. Early studies focused on the CPE produced by poliovirus (PV) and coxsackievirus (16,33,70) and revealed crystalline arrays of virus in the cytoplasm and viruses associated with, and contained within, membrane vesicles (7,10,43). The origin of vesicles induced by PV has been the subject of several studies with various conclusions. Highpressure freezing preparation for electron microscopy showed double-membrane vesicles in cells infected with PV (71). The vesicles are thought to be derived from the endoplasmic reticulum (ER), arising from either COPII-coated vesicles or autophagic vesicles (6,32,63,66,71,73,74). However, the presence of other organelle markers associated with PV vesicles, at later time points of infection, suggests that the ER is not the sole contributor of these membranes (66).In a previous publication (51), we reported that while footand-mouth disease virus (FMDV) induced the formation of membrane vesicles in infected cells, as observed in PV-infected cells, there were a number of differences between the effects observed with these two viruses. FMDV-induced vesicles predominantly had a single membrane and were not found in clusters as reported for PV. Further differences between PV and FMDV replication are seen in studies of virus sensitivity to the fungal metabolite, brefeldin A, which inhibits the function of Arf1-GTPase. Brefeldin A completely inhibits PV replication, whereas FMDV replication appears unaffected (15,22,30,48,51,58). Differences between PV and FMDV are also seen in some of the functions of the nonstructural proteins. Studies examining the effects of FMDV, and its nonstructural proteins, on the host-cell protein secretory pathway revealed that, unlike the PV 3A protein, FMDV 3A was unable to slow protein secretion (12,49). Interestingly, although both FMDV 2BC and PV 2BC are able to slow protein trafficking though the secretory pathway, they appear to act at different sites. PV 2BC is thought to slow the processing of secretory proteins at the Golgi body, whereas FMDV 2BC expression leads to retention of secretory proteins within the ER (2,19,49,50,64). Taken together, these observations indicate significant differences in the virus-host cell interactions of PV (an enterovirus) and FMDV (an aphthovirus).In contrast to the work on membrane vesicles, relatively little work has been reported on the effect of picornavirus infection on the cytoskeleton. However, it is becoming increasingly clear that many of these viruses use and modify the cytoskeleton for cell entry, replication, and egress. For example, Theiler's virus (a cardiovirus) has been reported to associate with intermediate filaments (55). PV has been reported to associate with the cytoskeleton and intermediate filaments (42,

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“…These changes include increased intracellular vesicle formation, increased membrane permeability, disrupted Ca 2+ balance in cells, cell apoptosis, and induced autophagy [5,13]. Some of these functional and morphological changes can also be observed in cells expressing the enteroviruscoded 2B protein only [9,13,18,19]. The viroporin features of the 2B protein that affect the biological functions of host cells are summarized in the following aspects.…”

Section: Effects Of the Ion Channel Activity Of Enterovirus 2b Proteimentioning

confidence: 99%

Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family

Sun

Guo

2014

Vet Res

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Viroporins are a group of transmembrane proteins with low molecular weight that are encoded by many animal viruses. Generally, viroporins are composed of 50-120 amino acid residues and possess a minimum of one hydrophobic region that interacts with the lipid bilayer and leads to dispersion. Viroporins are involved in destroying the morphology of host cells and disturbing their biological functions to complete the life cycle of the virus. The 2B proteins encoded by enteroviruses, which belong to the family Picornaviridae, can form transmembrane pores by oligomerization, increase the permeability of plasma membranes, disturb the homeostasis of calcium in cells, induce apoptosis, and cause autophagy; these abilities are shared among viroporins. The present paper introduces the structure and biological characteristics of various 2B proteins encoded by enteroviruses of the family Picornaviridae and may provide a novel idea for developing antiviral drugs.

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Plasma Membrane-porating Domain in Poliovirus 2B Protein. A Short Peptide Mimics Viroporin Activity

Cited by 37 publications

References 75 publications

Membrane Integration of Poliovirus 2B Viroporin

Membrane Integration of Poliovirus 2B Viroporin

Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3C ^pro

Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family

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Plasma Membrane-porating Domain in Poliovirus 2B Protein. A Short Peptide Mimics Viroporin Activity

Cited by 37 publications

References 75 publications

Membrane Integration of Poliovirus 2B Viroporin

Membrane Integration of Poliovirus 2B Viroporin

Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3C pro

Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family

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Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3C ^pro