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 Man-Specific, GalNAc/T/Tn-Specific and Neu5Ac-Specific Seaweed Lectins as Glycan Probes for the SARS-CoV-2 (COVID-19) Coronavirus

Marine Drugs ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. 543
Author(s):  
Annick Barre ◽  
Els J.M. Van Damme ◽  
Mathias Simplicien ◽  
Hervé Benoist ◽  
Pierre Rougé
Keyword(s):  
Influenza Virus ◽  
Antiviral Agents ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Complex Type ◽  
Enveloped Viruses ◽  
High Mannose ◽  
Hiv 1 ◽  
Biomedical Interest

Seaweed lectins, especially high-mannose-specific lectins from red algae, have been identified as potential antiviral agents that are capable of blocking the replication of various enveloped viruses like influenza virus, herpes virus, and HIV-1 in vitro. Their antiviral activity depends on the recognition of glycoprotein receptors on the surface of sensitive host cells—in particular, hemagglutinin for influenza virus or gp120 for HIV-1, which in turn triggers fusion events, allowing the entry of the viral genome into the cells and its subsequent replication. The diversity of glycans present on the S-glycoproteins forming the spikes covering the SARS-CoV-2 envelope, essentially complex type N-glycans and high-mannose type N-glycans, suggests that high-mannose-specific seaweed lectins are particularly well adapted as glycan probes for coronaviruses. This review presents a detailed study of the carbohydrate-binding specificity of high-mannose-specific seaweed lectins, demonstrating their potential to be used as specific glycan probes for coronaviruses, as well as the biomedical interest for both the detection and immobilization of SARS-CoV-2 to avoid shedding of the virus into the environment. The use of these seaweed lectins as replication blockers for SARS-CoV-2 is also discussed.

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 Water-SARS-CoV-2 Interaction-Based Mechanism Inhibiting Virus Attachment to Host Cells

2020 ◽  
Author(s):  
Valery Shalatonin
Keyword(s):  
Host Cell ◽  
Long Range ◽  
Influenza Viruses ◽  
Host Cells ◽  
Water Molecules ◽  
Uv Absorbance ◽  
Enveloped Viruses ◽  
Oh Groups ◽  
Water Interaction ◽  
Repulsive Forces

Many studies showed that the enveloped viruses, including coronaviruses, HIV-1, and influenza inactivate significantly faster in water than the non-enveloped viruses. It looks that there is a certain mechanism controlling this phenomenon. However, the epidemic spread of SARS-CoV-2 indicates that this virus – water interaction mechanism is not effective enough to fully inhibit coronavirus reproduction. We hypothesized that a spatially extended layer of the ordered water molecules, formed around CoV due to the spike’s glycans – surrounding water interaction acts as a buffer inhibiting CoV motion and its attachment to the host cell receptor. There is experimental evidence that water molecules while interacting with glucans experience the long-range ordering and repulsive forces. Our findings revealed new features that can promote its interaction. It was shown that the glycans and water molecules have the same far ultraviolet (UV) absorbance peak at ~185 nm. This peak is a manifestation of the still little-known physical properties possessed by hydroxyl (OH) groups, including those contained in glycans and water molecules. Many studies show that the carbohydrate hydroxyl groups are a key element in the long-range antifreeze glycoproteins activity which is closely correlated with our issue. To further increase ice inhibition, a sugar-based (usually trehalose) water solution, further slowing down the water dynamics is commonly used. Our experiments with sugar-based compounds dissolved in water showed that in such solutions the UV absorbance at ~185 nm (activity of the OH groups) can be essentially increased with respect to the bulk water. The spike’s glycans – water long-range interaction, activated due to the dissolved sugar-based compound, creates the glass-like stabilizing hydration layer (like in case of the trehalose) effectively inhibiting the virus – host cell binding. It was shown that the chemical structures of the known compounds with proven inhibition of SARS-CoV-2 entry into host cells agree with our findings. The described approach can be effective against human immunodeficiency viruses, influenza viruses, and possibly other enveloped viruses. <br>

scholarly journals Curvature Concentrations on the HIV-1 Capsid

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Jiangguo Liu ◽  
Farrah Sadre-Marandi ◽  
Simon Tavener ◽  
Chaoping Chen
Keyword(s):  
Host Cell ◽  
Capsid Proteins ◽  
Quantitative Characterization ◽  
Viral Capsids ◽  
Virus Capsids ◽  
Hiv 1

AbstractIt is known that the retrovirus capsids possess a fullerene-like structure. These caged polyhedral arrangements are built entirely from hexagons and exactly 12 pentagons according to the Euler theorem. Viral capsids are composed of capsid proteins, which create the hexagon and pentagon shapes by groups of six (hexamer) and five (pentamer) proteins. Different distributions of these 12 pentamers result in icosahedral, tubular, or conical shaped capsids. These pentamer clusters introduce declination and hence curvature on the capsids. This paper provides explicit and quantitative characterization of curvature on virus capsids. The concept of curvature concentration is also introduced. For the HIV (5,7)-cone, it is shown that the curvature concentration at the narrow end is about at least four times higher than that at the broad end. Our modeling results about curvature concentrations on HIV-1 capsids echo the results in the literature that the pentamers are in the regions with the highest stress, although the connection between the two approaches (curvature concentration and stress) is to be explored. This also leads to a conjecture that “HIV-1 capsid narrow end may close last during maturation but open first during entry into a host cell".

Antiviral Activity of a Sulphated Polysaccharide Extracted from the Marine Pseudomonas and Marine Plant Dinoflagellata against Human Immunodeficiency Viruses and other Enveloped Viruses

1996 ◽  
Vol 7 (4) ◽  
pp. 189-196 ◽  
Author(s):  
K. Hashimoto ◽  
E. Kodama ◽  
S. Mori ◽  
J. Watanabe ◽  
M. Baba ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Virus Type ◽  
Measles Virus ◽  
Host Cells ◽  
Enveloped Viruses ◽  
Sulphated Polysaccharide ◽  
Marine Plant ◽  
Syncytial Virus ◽  
Hiv 1

A natural sulphated mucopolysaccharide (OKU40), extracted from a marine plant Dinoflagellata, and an artificial sulphated polysaccharide (OKU41), prepared from a marine Pseudomonas, displayed antiviral activities against several enveloped viruses. OKU40 and OKU41 were found to be homogenous in electrophoresis and sedimation velocity and had a molecular weight of 8.0 × 1065.0 × 105respectively. The sulphation rate of OKU40 and OKU41 was 8.9% and 5.4%, respectively. Each OKU40 and OKU41 inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2) and zidovudineresistant HIV-1 in MT-4 cells at similar concentrations to those of dextran sulphate (molecular weight: 5000) (50% inhibitory concentrations: 0.86-1.95 μg mL−1), whereas these compounds did not affect the growth and viability of mock-infected MT-4 cells at concentrations up to 500 μg mL−1. These compounds proved inhibitory not only to HIV-1 and HIV-2 but also to other enveloped viruses, i.e. herpes simplex virus type 1, influenza virus A and B, respiratory syncytial virus and measles virus. OKU40 and OKU41 suppressed syncytium formation induced by cocultivation of MOLT-4/IIIb and MOLT-4 cells at concentrations higher than 20 μg mL−1. Although OKU41 inhibited the binding of HIV-1 to the host cells and the binding of anti-gp120 monoclonal antibody to HIV-1 gp120, OKU40 did not inhibit these bindings, suggesting that the mechanism of anti-HIV activity of OKU40 and OKU41 may be primarily due to the inhibition of virus-cell fusion and viral adsorption to the host cells, respectively. Furthermore, these compounds did not inhibit to the blood coagulation process at a concentration that was significantly inhibitory to HIV replication. The compounds appear to have an interesting potential as virucidal agents.

Coxsackievirus B transmission and possible new roles for extracellular vesicles

2013 ◽  
Vol 41 (1) ◽  
pp. 299-302 ◽  
Author(s):  
Jameel M. Inal ◽  
Samireh Jorfi
Keyword(s):  
Calcium Concentration ◽  
Rna Virus ◽  
Extracellular Vesicle ◽  
Host Cells ◽  
Physical Interaction ◽  
Enveloped Viruses ◽  
Coxsackievirus B ◽  
Infected Cells ◽  
Adenovirus Receptor ◽  
Hiv 1

Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent evidence indicates that virus spread to secondary sites is not only achieved by a lytic mechanism and a non-lytic cell–cell strategy has been suggested for coxsackievirus B3. A physical interaction between infected and non-infected cells has been shown to be an efficient mechanism for retroviral transmission and one type of extracellular vesicle, the exosome, has been implicated in HIV-1 transmission. HIV-1 also takes advantage of depolymerization of actin for spread between T-cells. Calpain-mediated depolymerization of the actin cytoskeleton, as a result of increases in intracellular calcium concentration during coxsackievirus infection, would result in a release of host cell-derived microvesicles. If so, we speculate that maybe such microvesicles, increasingly recognized as major vehicles mediating intercellular communication, could play a role in the intercellular transmission of non-enveloped viruses.

scholarly journals Targeting the Fusion Process of SARS-CoV-2 Infection by Small Molecule Inhibitors

mBio ◽  
2022 ◽  
Author(s):  
Seung Bum Park ◽  
Parker Irvin ◽  
Zongyi Hu ◽  
Mohsin Khan ◽  
Xin Hu ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Host Cells ◽  
Fusion Process ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Fusion Inhibitors

SARS-CoV-2 is an enveloped virus that requires membrane fusion for entry into host cells. Since the fusion process is relatively conserved among enveloped viruses, we tested our HCV fusion inhibitors, dichlorcyclizine and fluoxazolevir, against SARS-CoV-2.

scholarly journals Water-SARS-CoV-2 Interaction-Based Mechanism Inhibiting Virus Attachment to Host Cells

2020 ◽  
Author(s):  
Valery Shalatonin
Keyword(s):  
Host Cell ◽  
Long Range ◽  
Influenza Viruses ◽  
Host Cells ◽  
Water Molecules ◽  
Uv Absorbance ◽  
Enveloped Viruses ◽  
Oh Groups ◽  
Water Interaction ◽  
Repulsive Forces

Many studies showed that the enveloped viruses, including coronaviruses, HIV-1, and influenza inactivate significantly faster in water than the non-enveloped viruses. It looks that there is a certain mechanism controlling this phenomenon. However, the epidemic spread of SARS-CoV-2 indicates that this virus – water interaction mechanism is not effective enough to fully inhibit coronavirus reproduction. We hypothesized that a spatially extended layer of the ordered water molecules, formed around CoV due to the spike’s glycans – surrounding water interaction acts as a buffer inhibiting CoV motion and its attachment to the host cell receptor. There is experimental evidence that water molecules while interacting with glucans experience the long-range ordering and repulsive forces. Our findings revealed new features that can promote its interaction. It was shown that the glycans and water molecules have the same far ultraviolet (UV) absorbance peak at ~185 nm. This peak is a manifestation of the still little-known physical properties possessed by hydroxyl (OH) groups, including those contained in glycans and water molecules. Many studies show that the carbohydrate hydroxyl groups are a key element in the long-range antifreeze glycoproteins activity which is closely correlated with our issue. To further increase ice inhibition, a sugar-based (usually trehalose) water solution, further slowing down the water dynamics is commonly used. Our experiments with sugar-based compounds dissolved in water showed that in such solutions the UV absorbance at ~185 nm (activity of the OH groups) can be essentially increased with respect to the bulk water. The spike’s glycans – water long-range interaction, activated due to the dissolved sugar-based compound, creates the glass-like stabilizing hydration layer (like in case of the trehalose) effectively inhibiting the virus – host cell binding. It was shown that the chemical structures of the known compounds with proven inhibition of SARS-CoV-2 entry into host cells agree with our findings. The described approach can be effective against human immunodeficiency viruses, influenza viruses, and possibly other enveloped viruses. <br>

scholarly journals Full scale structural, mechanical and dynamical properties of HIV-1 liposomes.

2021 ◽  
Author(s):  
Alexander Bryer ◽  
Edward Lyman ◽  
Tyler Reddy ◽  
Juan Roberto Perilla
Keyword(s):  
Life Cycle ◽  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Md Simulations ◽  
Full Scale ◽  
Bending Rigidity ◽  
Dynamical Properties ◽  
The Rich ◽  
Viral Envelopes ◽  
Hiv 1

Enveloped viruses are enclosed by a lipid membrane inside of which are all of the components necessary for the virus life cycle; viral proteins, the viral genome and metabolites. Viral envelopes are lipid bilayers that adopt morphologies ranging from spheres to tubes. The envelope is derived from the host cell during viral replication. Thus, the composition of the bilayer depends on the complex constitution of lipids from the host cell's organelle(s) where assembly and/or budding of the viral particle occurs. Here, molecular dynamics (MD) simulations of authentic, asymmetric HIV-1 liposomes are used to derive a unique level of resolution of its full scale structure, mechanics and dynamics. Analysis of the structural properties reveal the distribution of thicknesses of the bilayers over the entire liposome as well as its global fluctuations. Moreover, full-scale mechanical analyses are employed to derive the global bending rigidity of HIV-1 liposomes. Finally, dynamical properties of the lipid molecules reveal important relationships between their 3D diffusion, the location of lipid-rafts and the asymmetrical composition of the envelope. Overall, our simulations reveal complex relationships between the rich lipid composition of the HIV-1 liposome and its structural, mechanical and dynamical properties with critical consequences to different stages of HIV-1's life cycle.

scholarly journals BST-2 Diminishes HIV-1 Infectivity

2010 ◽  
Vol 84 (23) ◽  
pp. 12336-12343 ◽  
Author(s):  
Jianyong Zhang ◽  
Chen Liang
Keyword(s):  
Stromal Cell ◽  
Bone Marrow Stromal Cell ◽  
Host Cells ◽  
Viral Protease ◽  
Enveloped Viruses ◽  
Marrow Stromal Cell ◽  
Virus Particles ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin/CD317/HM1.24) inhibits the release of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses by tethering virus particles to the cell surface. In this study, we provide evidence not only that the yield of cell-free HIV-1 particles is significantly reduced by BST-2 but also that the infectivity of these progeny virions is severely impaired. The lowered virion infectivity is due to the accumulation of pr55 Gag precursor and the p40Gag intermediates as well as to the loss of a mature core in the majority of HIV-1 particles. These data suggest that, in addition to impeding the release of HIV-1 particles from host cells, BST-2 may also interfere with the activation of viral protease and, as a result, impairs viral Gag processing as well as maturation of HIV-1 particles.

Sign in / Sign up

Export Citation Format

Share Document