Faculty Opinions recommendation of Structural rearrangement within an enveloped virus upon binding to the host cell.

2008 ◽  
Author(s):  
Greg Smith
Keyword(s):  
Host Cell ◽  
Structural Rearrangement ◽  
Enveloped Virus

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 Structural Rearrangement within an Enveloped Virus upon Binding to the Host Cell

2008 ◽  
Vol 82 (21) ◽  
pp. 10429-10435 ◽  
Author(s):  
David G. Meckes ◽  
John W. Wills
Keyword(s):  
Cell Attachment ◽  
Structural Rearrangement ◽  
Viral Envelope ◽  
Viral Glycoprotein ◽  
Glycoprotein C ◽  
Enveloped Virus ◽  
Host Signaling ◽  
Infected Cells ◽  
Internal Change ◽  
Simplex Virus

ABSTRACT We have made the surprising discovery that the interactions of herpes simplex virus with its initial cell attachment receptor induce a rapid and highly efficient structural change in the tegument, the region of the virion situated between the membrane and the capsid. It has been known for nearly a decade that viruses can trigger host signaling pathways when they bind to receptors on the cell surface; however, until now there has been no evidence that a signal can be sent in reverse—from the “outside in”—across a viral membrane. Evidence for this signaling event was found during studies of UL16, a tegument protein that is conserved among all the herpesviruses. Previous work has demonstrated that UL16 is bound to capsids isolated from the cytoplasm of infected cells, but this interaction is destabilized during subsequent egress steps, leading to release of the extracellular virion. Pretreatment with N-ethylmaleimide, a small, membrane-permeating compound that covalently modifies free cysteines, restabilizes the interaction, thereby permitting the capsid-UL16 complex to be isolated following disruption of virions with NP-40. In the experiments described here, we found that the natural signal for release of UL16 from capsids is sent when virions merely bind to cells at 4°C. The internal change was also observed upon binding to immobilized heparin in a manner that requires viral glycoprotein C. This represents the first example of signaling across a viral envelope following receptor binding.

scholarly journals Chikungunya virus requires an intact microtubule network for efficient viral genome delivery

2020 ◽  
Author(s):  
Tabitha E. Hoornweg ◽  
Ellen M. Bouma ◽  
Denise P.I. van de Pol ◽  
Izabela A. Rodenhuis-Zybert ◽  
Jolanda M. Smit
Keyword(s):  
Host Cell ◽  
Viral Genome ◽  
Intracellular Trafficking ◽  
Chikungunya Virus ◽  
Antiviral Treatment ◽  
Cell Entry ◽  
Cell Periphery ◽  
Microtubule Network ◽  
Enveloped Virus ◽  
Early Endosomes

AbstractChikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which has rapidly spread around the globe thereby causing millions of infections. CHIKV is an enveloped virus belonging to the Togaviridae family and enters its host cell primarily via clathrin-mediated endocytosis. Upon internalization, the endocytic vesicle containing the virus particle moves through the cell and delivers the virus to early endosomes where membrane fusion is observed. Thereafter, the nucleocapsid dissociates and the viral RNA is translated into proteins. In this study, we examined the importance of the microtubule network during the early steps of infection and dissected the intracellular trafficking behavior of CHIKV particles during cell entry. We observed two distinct CHIKV intracellular trafficking patterns prior to membrane hemifusion. Whereas half of the CHIKV virions remained static during cell entry and fused in the cell periphery, the other half showed fast-directed microtubule-dependent movement prior to delivery to Rab5-positive early endosomes and predominantly fused in the perinuclear region of the cell. Disruption of the microtubule network reduced the number of infected cells. At these conditions, membrane hemifusion activity was not affected yet fusion was restricted to the cell periphery. Furthermore, follow-up experiments revealed that disruption of the microtubule network impairs the delivery of the viral genome to the cell cytosol. We therefore hypothesize that microtubules may direct the particle to a cellular location that is beneficial for establishing infection or aids in nucleocapsid uncoating.Author SummaryChikungunya virus (CHIKV) is an alphavirus that is transmitted to humans by infected mosquitoes. Disease symptoms can include fever, rash, myalgia, and long-lasting debilitating joint pains. Unfortunately, there is currently no licensed vaccine or antiviral treatment available to combat CHIKV. Understanding the virus:host interactions during the replication cycle of the virus is crucial for the development of effective antiviral therapies. In this study we elucidated the trafficking behavior of CHIKV particles early in infection. During cell entry, CHIKV virions require an intact microtubule network for efficient delivery of the viral genome into the host cell thereby increasing the chance to productively infect a cell.

scholarly journals Inhibiting fusion with cellular membrane system: therapeutic options to prevent severe acute respiratory syndrome coronavirus-2 infection

2020 ◽  
Vol 319 (3) ◽  
pp. C500-C509
Author(s):  
Prasenjit Mitra
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Cell ◽  
Membrane System ◽  
Cell Receptor ◽  
Cellular Membrane ◽  
Therapeutic Options ◽  
Viral Fusion ◽  
Enveloped Virus ◽  
Host Cell Receptor ◽  
Endogenous Proteases

Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped virus with a positive-sense single-stranded RNA genome, facilitates the host cell entry through intricate interactions with proteins and lipids of the cell membrane. The detailed molecular mechanism involves binding to the host cell receptor and fusion at the plasma membrane or after being trafficked to late endosomes under favorable environmental conditions. A crucial event in the process is the proteolytic cleavage of the viral spike protein by the host’s endogenous proteases that releases the fusion peptide enabling fusion with the host cellular membrane system. The present review details the mechanism of viral fusion with the host and highlights the therapeutic options that prevent SARS-CoV-2 entry in humans.

scholarly journals Structural Insight into Non-Enveloped Virus Binding to Glycosaminoglycan Receptors: A Review

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 800
Author(s):  
Marie N. Sorin ◽  
Jasmin Kuhn ◽  
Aleksandra C. Stasiak ◽  
Thilo Stehle
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Structural Information ◽  
Sialic Acids ◽  
Virus Binding ◽  
Enveloped Virus ◽  
Charged Amino Acids ◽  
Current State ◽  
Human Viruses ◽  
Viral Receptors

Viruses are infectious agents that hijack the host cell machinery in order to replicate and generate progeny. Viral infection is initiated by attachment to host cell receptors, and typical viral receptors are cell-surface-borne molecules such as proteins or glycan structures. Sialylated glycans (glycans bearing sialic acids) and glycosaminoglycans (GAGs) represent major classes of carbohydrate receptors and have been implicated in facilitating viral entry for many viruses. As interactions between viruses and sialic acids have been extensively reviewed in the past, this review provides an overview of the current state of structural knowledge about interactions between non-enveloped human viruses and GAGs. We focus here on adeno-associated viruses, human papilloma viruses (HPVs), and polyomaviruses, as at least some structural information about the interactions of these viruses with GAGs is available. We also discuss the multivalent potential for GAG binding, highlighting the importance of charged interactions and positively charged amino acids at the binding sites, and point out challenges that remain in the field.

scholarly journals A newly identified protein complex that mediates white spot syndrome virus infection via chitin-binding protein

2014 ◽  
Vol 95 (8) ◽  
pp. 1799-1808 ◽  
Author(s):  
Po-Yu Huang ◽  
Jiann-Horng Leu ◽  
Li-Li Chen
Keyword(s):  
Cell Membrane ◽  
Host Cell ◽  
Protein Complex ◽  
White Spot Syndrome Virus ◽  
Binding Protein ◽  
Envelope Proteins ◽  
White Spot ◽  
Host Cell Membrane ◽  
Enveloped Virus ◽  
Chitin Binding Protein

White spot syndrome virus (WSSV) is a large enveloped virus which has caused severe mortality and huge economic losses in the shrimp farming industry. The enveloped virus must be combined with the receptors of the host cell membrane by the virus envelope proteins. In the case of WSSV, binding of envelope proteins with receptors of the host cell membrane was discovered in a number of previous studies, such as VP53A and 10 other proteins with chitin-binding protein (CBP), VP28 with Penaeus monodon Rab7, VP187 with β-integrin, and so on. WSSV envelope proteins were also considered capable of forming a protein complex dubbed an ‘infectome’. In this study, the research was focused on the role of CBP in the WSSV infection process, and the relationship between CBP and the envelope proteins VP24, VP28, VP31, VP32 VP39B, VP53A and VP56. The results of the reverse transcription-PCR analyses showed that CBP existed in a variety of shrimp. The speed of WSSV infection could be slowed down by inhibiting CBP gene expression. Far-Western blot analysis and His pull-down assays were conducted, and a protein complex was found that appeared to be composed of a ‘linker’ protein consisting of VP31, VP32 and VP39B together with four envelope proteins, including VP24, VP28, VP53A and VP56. This protein complex was possibly another part of the infectome and the possible binding region with CBP. The findings of this study may have identified certain points for further WSSV research.

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.

Structure-function relationship of the influenza fusion peptide

2017 ◽  
Vol 5 ◽  
pp. 27-35
Author(s):  
Anna Szymaniec ◽  
Remigiusz Worch
Keyword(s):  
Host Cell ◽  
Influenza A ◽  
Genetic Material ◽  
Fusion Peptide ◽  
Phospholipid Bilayer ◽  
Enveloped Virus ◽  
Peptide Length ◽  
Helical Hairpin ◽  
Dynamics Simulations ◽  
Membrane Components

Influenza is an enveloped virus which enters the host cell through en-docytosis-mediated mechanism. To enable the release genetic material, a process of fusion between viral and host cell membranes occurs, which is mediated by influenza hemagglutinin (HA) protein. The N-terminal fragment of hemagglutinin HA2 subunit, directly interacting with the membrane, is named a fusion peptide (HAfp), since it is able to promote fusion also as a synthetic fragment. Its C-terminal part contains three residues (W21-Y22-G23), which are highly conserved among various serotypes of Influenza A. It has been shown that the peptide length has an influence on its structure: HAfp1-20 forms a boomerangin contrast to a tight helical hairpin formed by HAfp1-23. To gain more insight into the role of the conserved residues, we studied the effect of peptide length on fusion properties, its structural dynamics, and par-titioning to the phospholipid bilayer. By means of molecular dynamics simulations and spectroscopic measurements, we showed that the presence of three C-terminal residues in HAfp1-23 promotes the for-mation of hairpin structure. In contrast to less structured HAfp1-20,it orients perpendicularly to the membrane plane and induces more disorder in the surrounding lipids. Using a novel fusion visualization assay based on FLIM microscopy on giant unilamellar vesicles (GUV), we observed that HAfp1-23 promotes fusion to a higher extent than HAfp1-20. Moreover, we report cholesterolenriched domain formation exclusively by the longer fusion peptide. This redistribution of membrane components in fluid phases is likely to play a role during membrane fusion.

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