Special Issue "Viral Glycoprotein Structure"

A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (30 September 2015).

Special Issue Editor

Dr. Andrew Ward
E-Mail
Guest Editor
Department of Integrative Structural and Computational Biology California Campus, The SCRIPPS Research Institute, La Jolla, CA, USA
Interests: viral glycoproteins, viral receptors, HIV-1, influenza, Ebola, electron microscopy, vaccines, antibody therapeutics, structural biology, biophysics, electron microscopy

Special Issue Information

Dear Colleagues,

Viral glycoproteins reside on the surface of virions and are often the sole component of the virus that interacts with the external environment. As such they must recognize appropriate host cells and initiate infection, either through membrane fusion or endocytosis, all while escaping detection by the immune system of animals.  These multi-functional machines represent some of the most exciting but difficult protein complexes to structurally characterize. A number of technological breakthroughs have enabled increasingly detailed studies of these proteins, and with them a greater understanding of the viral fusion machinery and its interplay with antibodies, which have played a critical role in facilitating these studies. The glycans on the surface of viral glycoproteins are host derived and utilized by the virus to mimic the host and evade detection of the immune system. In many cases antibodies can still be generated either by avoiding the glycans (e.g. flu) or by incorporating them into epitopes (e.g. HIV). The rapid mutability of viruses coupled to immune pressure typically results in highly variable surfaces, resulting in a complex co-evolution between virus and host. The challenge then for structural biologists is to hit these moving targets.  By combining a wide array of technologies and data types well-determined models of viral glycoprotein structure, function, and dynamics are attainable. The goal of this issue is to highlight the state of the art in viral glycoprotein structure and function that have been enabled by recent technological and methodological advances.

Dr. Andrew Ward
Guest Editor

Manuscript Submission Information

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Keywords

  • virus
  • glycoprotein structure
  • glycan
  • envelope
  • capsid
  • viral entry
  • host recognition
  • antibody

Published Papers (6 papers)

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Research

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Open AccessArticle
Subcellular Trafficking and Functional Relationship of the HSV-1 Glycoproteins N and M
Viruses 2016, 8(3), 83; https://doi.org/10.3390/v8030083 - 17 Mar 2016
Cited by 8
Abstract
The herpes simplex virus type 1 (HSV-1) glycoprotein N (gN/UL49.5) is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM [...] Read more.
The herpes simplex virus type 1 (HSV-1) glycoprotein N (gN/UL49.5) is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM and gN are covalently linked by a single disulphide bond formed between cysteine 46 of gN and cysteine 59 of gM. Exit of gN from the endoplasmic reticulum requires the N-terminal core of gM composed of eight transmembrane domains but is independent of the C-terminal extension of gM. Co-transport of gN and gM to the trans Golgi network also occurs upon replacement of conserved cysteines in gM and gN, suggesting that their physical interaction is mediated by covalent and non-covalent forces. Deletion of gN/UL49.5 using bacterial artificial chromosome (BAC) mutagenesis generated mutant viruses with wild-type growth behaviour, while full deletion of gM/UL10 resulted in an attenuated phenotype. Deletion of gN/UL49.5 in conjunction with various gM/UL10 mutants reduced average plaque sizes to the same extent as either single gM/UL10 mutant, indicating that gN is nonessential for the function performed by gM. We propose that gN functions in gM-dependent as well as gM-independent processes during which it is complemented by other viral factors. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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Review

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Open AccessReview
Dynamic Viral Glycoprotein Machines: Approaches for Probing Transient States That Drive Membrane Fusion
Viruses 2016, 8(1), 15; https://doi.org/10.3390/v8010015 - 11 Jan 2016
Cited by 5
Abstract
The fusion glycoproteins that decorate the surface of enveloped viruses undergo dramatic conformational changes in the course of engaging with target cells through receptor interactions and during cell entry. These refolding events ultimately drive the fusion of viral and cellular membranes leading to [...] Read more.
The fusion glycoproteins that decorate the surface of enveloped viruses undergo dramatic conformational changes in the course of engaging with target cells through receptor interactions and during cell entry. These refolding events ultimately drive the fusion of viral and cellular membranes leading to delivery of the genetic cargo. While well-established methods for structure determination such as X-ray crystallography have provided detailed structures of fusion proteins in the pre- and post-fusion fusion states, to understand mechanistically how these fusion glycoproteins perform their structural calisthenics and drive membrane fusion requires new analytical approaches that enable dynamic intermediate states to be probed. Methods including structural mass spectrometry, small-angle X-ray scattering, and electron microscopy have begun to provide new insight into pathways of conformational change and fusion protein function. In combination, the approaches provide a significantly richer portrait of viral fusion glycoprotein structural variation and fusion activation as well as inhibition by neutralizing agents. Here recent studies that highlight the utility of these complementary approaches will be reviewed with a focus on the well-characterized influenza virus hemagglutinin fusion glycoprotein system. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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Open AccessReview
Herpesvirus gB: A Finely Tuned Fusion Machine
Viruses 2015, 7(12), 6552-6569; https://doi.org/10.3390/v7122957 - 11 Dec 2015
Cited by 36
Abstract
Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, [...] Read more.
Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, these functions are distributed among multiple proteins: the conserved fusogen gB, the conserved gH/gL heterodimer of poorly defined function, and various non-conserved receptor-binding proteins. We summarize what is currently known about gB from two closely related herpesviruses, HSV-1 and HSV-2, with emphasis on the structure of the largely uncharted membrane interacting regions of this fusogen. We propose that the unusual mechanism of herpesvirus fusion could be linked to the unique architecture of gB. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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Open AccessReview
Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1
Viruses 2015, 7(9), 5115-5132; https://doi.org/10.3390/v7092856 - 18 Sep 2015
Cited by 26
Abstract
The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus [...] Read more.
The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus aggregation, are known. The interplay between virus neutralization and Fc-mediated effector function in protection against HIV-1 is complex and only partially understood. Passive immunization studies using potent broadly neutralizing antibodies (bnAbs) show that both neutralization and Fc-mediated effector function provides the widest dynamic range of protection; however, a vaccine to elicit these responses remains elusive. By contrast, active immunization studies in both humans and non-human primates using HIV-1 vaccine candidates suggest that weakly neutralizing or non-neutralizing antibodies can protect by Fc-mediated effector function, albeit with a much lower dynamic range seen for passive immunization with bnAbs. HIV-1 has evolved mechanisms to evade each type of antibody-mediated protection that must be countered by a successful AIDS vaccine. Overcoming the hurdles required to elicit bnAbs has become a major focus of HIV-1 vaccine development. Here, we discuss a less studied problem, the structural basis of protection (and its evasion) by antibodies that protect only by potent Fc-mediated effector function. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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Open AccessReview
Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design
Viruses 2015, 7(7), 3995-4046; https://doi.org/10.3390/v7072809 - 17 Jul 2015
Cited by 31
Abstract
In the 26 years since the discovery of Hepatitis C virus (HCV) a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA) regimens with >90% cure rates have [...] Read more.
In the 26 years since the discovery of Hepatitis C virus (HCV) a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA) regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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Open AccessReview
Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters
Viruses 2015, 7(7), 3506-3529; https://doi.org/10.3390/v7072783 - 29 Jun 2015
Cited by 12
Abstract
Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on [...] Read more.
Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field. Full article
(This article belongs to the Special Issue Viral Glycoprotein Structure)
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