scholarly journals Budding of Enveloped Viruses: Interferon-Induced ISG15—Antivirus Mechanisms Targeting the Release Process

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Eun Joo Seo ◽  
Jonathan Leis
Keyword(s):  
Innate Immunity ◽  
Host Cell ◽  
Virus Spread ◽  
Release Process ◽  
Enveloped Viruses ◽  
Viral Membrane ◽  
Enveloped Virus ◽  
Recent Advances ◽  
The Subject ◽  
Natural Target

Pathogenic strains of viruses that infect humans are encapsulated in membranes derived from the host cell in which they infect. After replication, these viruses are released by a budding process that requires cell/viral membrane scission. As such, this represents a natural target for innate immunity mechanisms to interdict enveloped virus spread and recent advances in this field will be the subject of this paper.

scholarly journals Gaussian curvature and the budding kinetics of enveloped viruses

2018 ◽  
Author(s):  
Sanjay Dharmavaram ◽  
Baochen She ◽  
Guillermo Lázaro ◽  
Michael F. Hagan ◽  
Robijn Bruinsma
Keyword(s):  
Host Cell ◽  
Lipid Bilayers ◽  
Energy Barrier ◽  
Lipid Membrane ◽  
Gauss Curvature ◽  
Host Cells ◽  
Capsid Proteins ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Hiv 1

AbstractThe formation of a membrane-enveloped virus such as HIV-1 starts with the assembly of a curved layer of capsid proteins lining the interior of the plasma membrane (PM) of the host cell. This layer grows into a spherical shell enveloped by a lipid membrane that is connected to the PM via a curved neck (“budding”). For many enveloped viruses the scission of this neck is not spontaneous. Instead, the elaborate “ESCRT” cell machinery needs to be recruited to carry out that task. It is not clear why this is necessary since scission is spontaneous for much simpler systems, such as vesiculation driven by phase-separation inside lipid bilayers. Recently, Brownian dynamics simulations of enveloped virus budding reproduced protracted pausing and stalling after formation of the neck [1], which suggest that the origin of pausing/stalling is to be found in the physics of the budding process. Here, we show that the pausing/stalling observed in the simulations can be understood as a purely kinetic phenomenon associated with a “geometrical” energy barrier that must be overcome by capsid proteins diffusing along the membrane prior to incorporation into the viral capsid. This geometrical energy barrier is generated by the conflict between the positive Gauss curvature of the capsid and the large negative Gauss curvature of the neck region. The theory is compared with the Brownian simulations of the budding of enveloped viruses.Author summaryDespite intense study, the life-cycle of the HIV-1 virus continues to pose mysteries. One of these concerns the assembly of the HIV-1 virus inside infected host cells: it is interrupted at the very last moment. During the subsequent pause, HIV-1 recruits a complex cell machinery, the so-called “ESCRT pathway”. The ESCRT proteins pinch-off the “viral bud” from the host cell. In this paper, we propose that the reason for the stalling emerges from the fundamental physics of the lipid membrane that surrounds the virus. The membrane mostly follows the spherical geometry of the virus, but in the pinch-off region the geometry is radically different: it resembles a neck. By combining numerical and analytical methods, we demonstrate that a neck geometry creates a barrier to protein entry, thus blocking proteins required to complete viral assembly. This “geometrical barrier” mechanism is general: such a barrier should form during assembly of all membrane-enveloped viruses – including the Ebola and Herpes viruses. Indeed many families of enveloped viruses also recruit the ESCRT machinery for pinch-off. A fundamental understanding of the budding process could enable a new strategy to combat enveloped viruses, based on selective stabilization of membrane neck geometries.

scholarly journals Electron Cryotomography of Tula Hantavirus Suggests a Unique Assembly Paradigm for Enveloped Viruses

2010 ◽  
Vol 84 (10) ◽  
pp. 4889-4897 ◽  
Author(s):  
Juha T. Huiskonen ◽  
Jussi Hepojoki ◽  
Pasi Laurinmäki ◽  
Antti Vaheri ◽  
Hilkka Lankinen ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Hemorrhagic Fever ◽  
Membrane Curvature ◽  
Emerging Viruses ◽  
Enveloped Viruses ◽  
Viral Membrane ◽  
Density Maps ◽  
Virion Structure ◽  
Electron Cryotomography ◽  
Assembly Principles

ABSTRACT Hantaviruses (family Bunyaviridae) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions are enveloped and contain a tripartite single-stranded negative-sense RNA genome. Two types of glycoproteins, GN and GC, are embedded in the viral membrane and form protrusions, or “spikes.” The membrane encloses a ribonucleoprotein core, which consists of the RNA segments, the nucleocapsid protein, and the RNA-dependent RNA polymerase. Detailed information on hantavirus virion structure and glycoprotein spike composition is scarce. Here, we have studied the structures of Tula hantavirus virions using electron cryomicroscopy and tomography. Three-dimensional density maps show how the hantavirus surface glycoproteins, membrane, and ribonucleoprotein are organized. The structure of the GN-GC spike complex was solved to 3.6-nm resolution by averaging tomographic subvolumes. Each spike complex is a square-shaped assembly with 4-fold symmetry. Spike complexes formed ordered patches on the viral membrane by means of specific lateral interactions. These interactions may be sufficient for creating membrane curvature during virus budding. In conclusion, the structure and assembly principles of Tula hantavirus exemplify a unique assembly paradigm for enveloped viruses.

scholarly journals A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion

2020 ◽  
Author(s):  
Thomas Labadie ◽  
Polly Roy
Keyword(s):  
Extracellular Vesicles ◽  
Defense Mechanism ◽  
Degradation Process ◽  
Free Virus ◽  
Enveloped Viruses ◽  
Virus Particles ◽  
Enveloped Virus ◽  
Super Infection

AbstractRecent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and observed that the majority of viruses are released in EVs, both in vitro and in the blood of infected animals. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome.Author summaryRecent discoveries of non-enveloped virus secreted in EVs opened the door to new developments in our understanding of the transmission and pathogenicity of these viruses. In particular, how these viruses hijack the host cellular secretion machinery, and the role of these EVs compared with free-virus particles remained to be explored. Here, we tackled these two aspects, by studying BTV, an emerging arthropod-borne virus causing epidemics worldwide. We showed that this virus is mainly released in EVs, in vivo and in the blood of infected animals, and that inhibition of the cell degradation machinery decreases the release of infectious EVs, but not free-virus particles. We found that BTV must neutralize the pH of lysosomes, which are important organelles of the cell degradation machinery, for efficient virus release in EVs. Our results highlight unique features for a virus released in EVs, explaining how BTV transits in lysosomes without being degraded. Interestingly, we observed that EVs are more infectious than free-virus particles, but only free-viruses are able to overcome the super-infection exclusion, which is a common cellular defense mechanism. In conclusion, our study stresses the dual role played by both forms, free and vesicular, in the virus life cycle.

scholarly journals Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection

2013 ◽  
Vol 20 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Peter Liehl ◽  
Vanessa Zuzarte-Luís ◽  
Jennie Chan ◽  
Thomas Zillinger ◽  
Fernanda Baptista ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Cell ◽  
Liver Stage ◽  
Stage Infection

Assessing the Benefit of Innovations in ATC

1998 ◽  
Vol 51 (3) ◽  
pp. 312-320
Author(s):  
S. Ratcliffe
Keyword(s):  
Free Flight ◽  
New Approaches ◽  
Quantitative Studies ◽  
Traffic Capacity ◽  
Recent Advances ◽  
The Subject

Recent advances in technology have encouraged proposals for new approaches to ATC in Europe and elsewhere. Two such proposals, both rather loosely framed, are for ‘free flight’ or for ‘seamless contracts’; otherwise ‘tubes of flight’. These concepts, and variations on them, aim to increase the traffic capacity of the airspace. They have been the subject of numerous published papers. Given the declared objects of these systems, it is surprising that, nearly without exception, these papers discuss the proposals only in qualitative terms. The present paper discusses idealised versions of these systems on the basis of quantitative studies. It is concluded that the ‘seamless contract’ is very probably unworkable in Europe. ‘free flight’ is workable in principle, but there is a need for investigation of possible mechanisms by which last-minute problems may be resolved.

scholarly journals Hemagglutinin-Mediated Membrane Fusion: A Biophysical Perspective

2018 ◽  
Vol 47 (1) ◽  
pp. 153-173 ◽  
Author(s):  
Sander Boonstra ◽  
Jelle S. Blijleven ◽  
Wouter H. Roos ◽  
Patrick R. Onck ◽  
Erik van der Giessen ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Host Cell ◽  
Conformational Changes ◽  
Fusion Process ◽  
Host Cell Membrane ◽  
Activation Barriers ◽  
Viral Membrane ◽  
Influenza Hemagglutinin ◽  
Working Together

Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion. Furthermore, we highlight the role of novel single-particle experiments and computational approaches in understanding the fusion process and their complementarity with other biophysical approaches.

The carbon-carbon triple bond as a tool to design organic semiconductors for photovoltaic applications: an assessment of prospects and challenges

2021 ◽  
Author(s):  
Mirko Seri ◽  
Assunta Marrocchi
Keyword(s):  
Organic Semiconductors ◽  
Triple Bond ◽  
Research Focus ◽  
Recent Advances ◽  
Photovoltaic Applications ◽  
The Subject ◽  
Intense Research

Alkyne-containing organic semiconductors are once again becoming the subject of intense research focus, and recent advances have significantly enhanced their performance in optoelectronics. This perspective focuses on the results achieved...

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