scholarly journals Atomistic Dynamics of a Viral Infection Process: Release of Membrane Lytic Peptides from a Non-Enveloped Virus

2021 ◽  
Author(s):  
Asis K Jana ◽  
Eric R May
Keyword(s):  
Physicochemical Characterization ◽  
Ph Control ◽  
Infection Process ◽  
Endocytic Pathway ◽  
Flock House Virus ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Functional Studies ◽  
Lytic Peptides ◽  
Experimental Findings

Molecular simulations have played an instrumental role in uncovering the structural dynamics and physical properties of virus capsids. In this work we move beyond equilibrium physicochemical characterization of a virus system to study a stage of the infection process which is required for viral proliferation. Despite many biochemical and functional studies, the molecular mechanism of host cell entry by non-enveloped viruses remains largely unresolved. Flock House Virus (FHV) is model system for non-enveloped viruses and is the subject of the current study. FHV infects through the acid-dependent endocytic pathway, where low pH triggers externalization of membrane disrupting (gamma) peptides from the capsid interior. Employing all-atom equilibrium and enhanced sampling simulations, the mechanism and energetics of gamma peptide liberation and the effect of pH on this process is investigated. Our computations agree with experimental findings and reveal nanoscopic details regarding the pH control mechanism which are not readily accessible in experiments.

scholarly journals Atomistic dynamics of a viral infection process: Release of membrane lytic peptides from a non-enveloped virus

2021 ◽  
Vol 7 (16) ◽  
pp. eabe1761
Author(s):  
Asis K. Jana ◽  
Eric R. May
Keyword(s):  
Physicochemical Characterization ◽  
Ph Control ◽  
Infection Process ◽  
Endocytic Pathway ◽  
Flock House Virus ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Functional Studies ◽  
Lytic Peptides ◽  
Experimental Findings

Molecular simulations have played an instrumental role in uncovering the structural dynamics and physical properties of virus capsids. In this work, we move beyond equilibrium physicochemical characterization of a virus system to study a stage of the infection process that is required for viral proliferation. Despite many biochemical and functional studies, the molecular mechanism of host cell entry by non-enveloped viruses remains largely unresolved. Flock House virus (FHV) is a model system for non-enveloped viruses and is the subject of the current study. FHV infects through the acid-dependent endocytic pathway, where low pH triggers externalization of membrane-disrupting (γ) peptides from the capsid interior. Using all-atom equilibrium and enhanced sampling simulations, the mechanism and energetics of γ peptide liberation and the effect of pH on this process are investigated. Our computations agree with experimental findings and reveal nanoscopic details regarding the pH control mechanism, which are not readily accessible in experiments.

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 Enhancement of Enveloped Virus Entry by Phosphatidylserine

2005 ◽  
Vol 79 (17) ◽  
pp. 11496-11500 ◽  
Author(s):  
David A. Coil ◽  
A. Dusty Miller
Keyword(s):  
Cultured Cells ◽  
Virus Entry ◽  
Cell Types ◽  
Virus Vector ◽  
Virus Binding ◽  
Virus Receptor ◽  
Enveloped Viruses ◽  
Virus Vectors ◽  
Enveloped Virus ◽  
Virus Fusion

ABSTRACT Enveloped virus vectors are used in a wide variety of applications. We have discovered that treatment of cultured cells with phosphatidylserine (PS) liposomes can increase virus vector infection by up to 20-fold. This effect does not abrogate virus receptor requirements, is specific to PS compared to other phospholipids, and is limited to enveloped viruses. Furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus fusion is enhanced. The liposomes are easily generated, store well, and allow enhanced infection with a variety of virus vectors and cell types.

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 Mechanisms of Methods for Hepatitis C Virus Inactivation

2014 ◽  
Vol 81 (5) ◽  
pp. 1616-1621 ◽  
Author(s):  
Stephanie Pfaender ◽  
Janine Brinkmann ◽  
Daniel Todt ◽  
Nina Riebesehl ◽  
Joerg Steinmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Infection Control ◽  
Viral Envelope ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Inactivation ◽  
Protection Assay ◽  
Uv Treatment ◽  
Enveloped Viruses ◽  
Enveloped Virus

ABSTRACTVirus inactivation by chemical disinfectants is an important instrument for infection control in medical settings, but the mechanisms involved are poorly understood. In this study, we systematically investigated the effects of several antiviral treatments on hepatitis C virus (HCV) particles as model for enveloped viruses. Studies were performed with authentic cell culture-derived viruses, and the influence of chemical disinfectants, heat, and UV treatment on HCV was analyzed by the determination of infectious particles in a limiting-dilution assay, by quantitative reverse transcription-PCR, by core enzyme-linked immunosorbent assay, and by proteolytic protection assay. All different inactivation methods resulted in a loss of HCV infectivity by targeting different parts of the virus particle. Alcohols such as ethanol and 2-propanol did not affect the viral RNA genome integrity but disrupted the viral envelope membrane in a capsid protection assay. Heat and UV treatment of HCV particles resulted in direct damage of the viral genome since transfection of viral particle-associated RNA into permissive cells did not initiate RNA replication. In addition, heat incubation at 80°C disrupted the HCV envelope, rendering the viral capsid susceptible to proteolytic digest. This study demonstrated the molecular processes of viral inactivation of an enveloped virus and should facilitate the development of effective disinfection strategies in infection control not only against HCV but also against other enveloped viruses.

scholarly journals SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101

2021 ◽  
Author(s):  
Elena Kudryashova ◽  
Ashley Zani ◽  
Geraldine Vilmen ◽  
Amit Sharma ◽  
Wuyuan Lu ◽  
...  
Keyword(s):  
Cell Culture ◽  
Innate Immune System ◽  
Infection Prevention ◽  
Bacterial Toxins ◽  
Innate Immune ◽  
Spike Protein ◽  
Prevention Strategies ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
High Concentrations

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins' ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil α-defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific α- and θ-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

EMCV Replication in BHK-21 in Vitro is Mediated by Caveolin-1, Actin, Dynamin-Dependent Endocytic Pathway

2020 ◽  
Author(s):  
Qiongyi Li ◽  
Yang Liu ◽  
Shujuan Xu ◽  
Kexue Zhao ◽  
Ying Ling ◽  
...  
Keyword(s):  
Virus Infection ◽  
Early Stage ◽  
Infection Process ◽  
Confocal Imaging ◽  
Endocytic Pathway ◽  
Virus Infectivity ◽  
Caveolin 1 ◽  
Chemical Inhibitors ◽  
Microscopy Analysis

Abstract Background: Encephalomycarditis virus is a member of Cardiovirus, belongs to the family Picornaviridae, and can infect different domestic and wild animals. However, the endocytic pathway by which EMCV infected BHK-21 cells remains unclear. In this study, endocytic pathway used by EMCV replication in BHK-21 cells was elucidated.Methods: The function of numerous cellular key factors implicated in the various endocytic mechanisms known to date were systematic detected using chemical inhibitors. Furthermore, RNA interference (RNAi) silencing, the overexpression of dominant protein combined to virus infectivity assays, and confocal imaging to examine which cellular molecules involved in the infection process were also analyzed.Results: The results indicated that the EMCV replication was related to endocytosis. However, neither clathrin nor macropinocytosis pathway was involved in virus infection. QRT-PCR and WB analyses showed that caveolin-1 were significantly up-regulated in EMCV infected BHK-21 cells. Immune-fluorescent confocal microscopy analysis showed that caveolin-1 was temporally co-localized with EMCV VP1 at the early stage of EMCV infection. Overexpressed caveolin-1 or downregulated caveolin-1 expression influenced the EMCV infection. Furthermore, EMCV infection was found to depend on dynamin and actin by chemical inhibitors resulted in diminished of virus infection.Conclusions: EMCV replication in BHK-21 cells via caveolin-1, dynamin, and actin-dependent endocytosis pathways.

Photodynamic inactivation of selected bovine viruses by isomeric cationic tetra-platinated porphyrins

2019 ◽  
Vol 23 (09) ◽  
pp. 1041-1046 ◽  
Author(s):  
Giovana Basso ◽  
Juliana F. Cargnelutti ◽  
Amanda L. Oliveira ◽  
Thiago V. Acunha ◽  
Rudi Weiblen ◽  
...  
Keyword(s):  
White Light ◽  
Light Irradiation ◽  
Photodynamic Inactivation ◽  
Virucidal Activity ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Led Array ◽  
Bovine Viruses

Porphyrin-based photodynamic processes have been used for the inactivation of microorganisms and treatment of tumors. The virucidal activity of porphyrins 3-PtTPyP and 4-PtTPyP was investigated against bovine viruses representative of the main structural groups (enveloped/non-enveloped, DNA/RNA: BVDV, BoHV-1, BAV and BEV), and against two epitheliotropic viruses (VSV and VACV). Viral suspensions were incubated at 0.91 [Formula: see text]mol [Formula: see text] L[Formula: see text] and exposed to a white-light LED array source (25 mW [Formula: see text] cm[Formula: see text]; 90 J [Formula: see text] cm[Formula: see text] for 0, 15, 30 and 60 min followed by determination of the remaining virus titers. Porphyrin 3-PtTPyP reduced almost 6 log of VSV and 3.5 log of BVDV titers after 15 min and complete virus photoinactivation was achieved after 30 min. 4-PtTPyP at 0.91 [Formula: see text]mol [Formula: see text] L[Formula: see text] produced reduction of titers of all enveloped virus depending on the time of light irradiation. No virucidal activity of any of the porphyrins was observed for non-enveloped viruses and these results showed the potential of porphyrins to inactivate viruses in premises.

scholarly journals The Interplay between ESCRT and Viral Factors in the Enveloped Virus Life Cycle

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 324
Author(s):  
Bo Meng ◽  
Andrew M. L. Lever
Keyword(s):  
Life Cycle ◽  
Surface Proteins ◽  
Cellular Functions ◽  
Enveloped Viruses ◽  
Endosomal Sorting ◽  
Diverse Families ◽  
Enveloped Virus ◽  
Virus Life Cycle ◽  
Obligate Parasites ◽  
Cellular Factors

Viruses are obligate parasites that rely on host cellular factors to replicate and spread. The endosomal sorting complexes required for transport (ESCRT) system, which is classically associated with sorting and downgrading surface proteins, is one of the host machineries hijacked by viruses across diverse families. Knowledge gained from research into ESCRT and viruses has, in turn, greatly advanced our understanding of many other cellular functions in which the ESCRT pathway is involved, e.g., cytokinesis. This review highlights the interplay between the ESCRT pathway and the viral factors of enveloped viruses with a special emphasis on retroviruses.

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