Viroporins

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 April 2015) | Viewed by 95239

Special Issue Editors


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Guest Editor
Biophysics Unit (CSIC-UPV/EHU) and Biochemistry Department, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain
Interests: viral products that destabilize host-cell membrane systems: fusion glycoproteins and viroporins

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Guest Editor
Centro de Biología Molecular Severo Ochoa (CSIC-UAM). c/Nicolás Cabrera, 1. Universidad Autónoma de Madrid. Cantoblanco. 28049 Madrid. Spain
Interests: membrane permeability; viral cytopathology; membrane trafficking; cytotoxic proteins; viral translation

Special Issue Information

Dear Colleagues:

Viroporins represent a group of proteins, encoded by animal virus genomes, which possess the ability to form pores in biological membranes. Animal viruses deleted of the viroporin gene are much less pathogenic and exhibit defects in the exit of progeny viruses from infected cells. During the past few years a number of key discoveries in the viroporin field have been achieved, including the description of additional viral products that fulfill viroporin functions. Several new insights into the molecular biology and the mode of action of the most conspicuous members of this protein family have been unveiled. Additionally, with regards to their structures, pores have been visualized by electron microscopy, and reconstructions from high-resolution structural data are, currently, also available. In addition, a number of avenues have been pursued to develop new compounds that block their activity. This special issue is not intended to provide a detailed view on each viroporin described thus far, instead, the focus will be set on the emerging general ideas and distinctive aspects of viroporin functioning and structure.

Dr. José Luis Nieva
Prof. Luis Carrasco
Guest Editors

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Keywords

  • viroporin
  • viral channel
  • cytopathic effect

Published Papers (10 papers)

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Editorial

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187 KiB  
Editorial
Viroporins: Structures and functions beyond cell membrane permeabilization
by José Luis Nieva and Luis Carrasco
Viruses 2015, 7(10), 5169-5171; https://doi.org/10.3390/v7102866 - 29 Sep 2015
Cited by 15 | Viewed by 4950
Abstract
Viroporins represent an interesting group of viral proteins that exhibit two sets of functions. First, they participate in several viral processes that are necessary for efficient production of virus progeny. [...] Full article
(This article belongs to the Special Issue Viroporins)

Research

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740 KiB  
Article
Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis
by Jose L. Nieto-Torres, Carmina Verdiá-Báguena, Carlos Castaño-Rodriguez, Vicente M. Aguilella and Luis Enjuanes
Viruses 2015, 7(7), 3552-3573; https://doi.org/10.3390/v7072786 - 3 Jul 2015
Cited by 61 | Viewed by 11150
Abstract
Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion [...] Read more.
Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. Full article
(This article belongs to the Special Issue Viroporins)
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Review

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1097 KiB  
Review
Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?
by Jamie Royle, Samuel John Dobson, Marietta Müller and Andrew Macdonald
Viruses 2015, 7(10), 5375-5387; https://doi.org/10.3390/v7102880 - 16 Oct 2015
Cited by 19 | Viewed by 7197
Abstract
Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes [...] Read more.
Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Full article
(This article belongs to the Special Issue Viroporins)
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769 KiB  
Review
Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin
by Vanesa Madan and Ralf Bartenschlager
Viruses 2015, 7(8), 4461-4481; https://doi.org/10.3390/v7082826 - 6 Aug 2015
Cited by 36 | Viewed by 13541
Abstract
The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication [...] Read more.
The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity. Full article
(This article belongs to the Special Issue Viroporins)
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934 KiB  
Review
Vpu Protein: The Viroporin Encoded by HIV-1
by María Eugenia González
Viruses 2015, 7(8), 4352-4368; https://doi.org/10.3390/v7082824 - 4 Aug 2015
Cited by 29 | Viewed by 10239
Abstract
Viral protein U (Vpu) is a lentiviral viroporin encoded by human immunodeficiency virus type 1 (HIV-1) and some simian immunodeficiency virus (SIV) strains. This small protein of 81 amino acids contains a single transmembrane domain that allows for supramolecular organization via homoligomerization or [...] Read more.
Viral protein U (Vpu) is a lentiviral viroporin encoded by human immunodeficiency virus type 1 (HIV-1) and some simian immunodeficiency virus (SIV) strains. This small protein of 81 amino acids contains a single transmembrane domain that allows for supramolecular organization via homoligomerization or interaction with other proteins. The topology and trafficking of Vpu through subcellular compartments result in pleiotropic effects in host cells. Notwithstanding the high variability of its amino acid sequence, the functionality of Vpu is well conserved in pandemic virus isolates. This review outlines our current knowledge on the interactions of Vpu with the host cell. The regulation of cellular physiology by Vpu and the validity of this viroporin as a therapeutic target are also discussed. Full article
(This article belongs to the Special Issue Viroporins)
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1301 KiB  
Review
Viroporins, Examples of the Two-Stage Membrane Protein Folding Model
by Luis Martinez-Gil and Ismael Mingarro
Viruses 2015, 7(7), 3462-3482; https://doi.org/10.3390/v7072781 - 26 Jun 2015
Cited by 15 | Viewed by 9045
Abstract
Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way [...] Read more.
Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly. Full article
(This article belongs to the Special Issue Viroporins)
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858 KiB  
Review
NLRP3 Inflammasome Activation by Viroporins of Animal Viruses
by Hui-Chen Guo, Ye Jin, Xiao-Yin Zhi, Dan Yan and Shi-Qi Sun
Viruses 2015, 7(7), 3380-3391; https://doi.org/10.3390/v7072777 - 24 Jun 2015
Cited by 32 | Viewed by 9221
Abstract
Viroporins are a group of low-molecular-weight proteins containing about 50–120 amino acid residues, which are encoded by animal viruses. Viroporins are involved in several stages of the viral life cycle, including viral gene replication and assembly, as well as viral particle entry and [...] Read more.
Viroporins are a group of low-molecular-weight proteins containing about 50–120 amino acid residues, which are encoded by animal viruses. Viroporins are involved in several stages of the viral life cycle, including viral gene replication and assembly, as well as viral particle entry and release. Viroporins also play an important role in the regulation of antiviral innate immune responses, especially in inflammasome formation and activation, to ensure the completion of the viral life cycle. By reviewing the research progress made in recent years on the regulation of the NLRP3 inflammasome by viroporins of animal viruses, we aim to understand the importance of viroporins in viral infection and to provide a reference for further research and development of novel antiviral drugs. Full article
(This article belongs to the Special Issue Viroporins)
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363 KiB  
Review
Viral Membrane Channels: Role and Function in the Virus Life Cycle
by ChingWooen Sze and Yee-Joo Tan
Viruses 2015, 7(6), 3261-3284; https://doi.org/10.3390/v7062771 - 23 Jun 2015
Cited by 26 | Viewed by 7211
Abstract
Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating [...] Read more.
Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’ replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence. Full article
(This article belongs to the Special Issue Viroporins)
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1445 KiB  
Review
Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?
by Jaume Torres, Wahyu Surya, Yan Li and Ding Xiang Liu
Viruses 2015, 7(6), 2858-2883; https://doi.org/10.3390/v7062750 - 4 Jun 2015
Cited by 19 | Viewed by 9469
Abstract
Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope [...] Read more.
Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity. Full article
(This article belongs to the Special Issue Viroporins)
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594 KiB  
Review
The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection
by To Sing Fung, Jaume Torres and Ding Xiang Liu
Viruses 2015, 7(6), 2834-2857; https://doi.org/10.3390/v7062749 - 4 Jun 2015
Cited by 48 | Viewed by 11531
Abstract
Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to [...] Read more.
Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed. Full article
(This article belongs to the Special Issue Viroporins)
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