scholarly journals Importance of Viral Late Domains in Budding and Release of Enveloped RNA Viruses

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1559
Author(s):  
Lisa Welker ◽  
Jean-Christophe Paillart ◽  
Serena Bernacchi
Keyword(s):  
Plasma Membrane ◽  
Viral Replication ◽  
Rna Viruses ◽  
Structural Proteins ◽  
Conserved Sequences ◽  
Membrane Fission ◽  
Virion Release ◽  
Current State ◽  
Different Types ◽  
Late Domains

Late assembly (L) domains are conserved sequences that are necessary for the late steps of viral replication, acting like cellular adaptors to engage the ESCRT membrane fission machinery that promote virion release. These short sequences, whose mutation or deletion produce the accumulation of immature virions at the plasma membrane, were firstly identified within retroviral Gag precursors, and in a further step, also in structural proteins of many other enveloped RNA viruses including arenaviruses, filoviruses, rhabdoviruses, reoviruses, and paramyxoviruses. Three classes of L domains have been identified thus far (PT/SAP, YPXnL/LXXLF, and PPxY), even if it has recently been suggested that other motifs could act as L domains. Here, we summarize the current state of knowledge of the different types of L domains and their cellular partners in the budding events of RNA viruses, with a particular focus on retroviruses.

scholarly journals Abrogating ALIX interactions results in stuttering of the ESCRT machinery

2019 ◽  
Author(s):  
Shilpa Gupta ◽  
Mourad Bendjennat ◽  
Saveez Saffarian
Keyword(s):  
Infectious Virus ◽  
G Protein Coupled Receptors ◽  
Cellular Proteins ◽  
Virus Release ◽  
Escrt Machinery ◽  
Membrane Fission ◽  
Virion Release ◽  
Robust Network ◽  
Late Domains ◽  
G Protein Coupled

ESCRTs are cellular proteins that catalyze the fission of membranes and play an important role in biology of disease including cancer and infectious virus release1. ESCRT associated protein ALIX plays an essential role in HIV budding2-4, exosome release5,6, down regulation of G-protein coupled receptors7, cytokinesis8,9and multi vesicular budding1. The consensus view is that ALIX plays a role by binding to the viral late domains2-4/Syntenin late domain5/Cepp558,9and helps recruit downstream protein CHMP42,8,10,11which along with VPS4 catalyzes the fission of the membrane12,13. Using live imaging we have visualized the recruitment of ALIX, CHMP4 and VPS4 during budding of HIV with abrogated Gag-ALIX interactions. Based on the canonical view, we were expecting to find reduced recruitment of ALIX under these conditions. Instead we report observing multiple rounds of transient recruitment of ALIX, CHMP4 and VPS4 prior to virion release. We further show that during each, transient recruitment, stoichiometry of all ESCRT components remained the same regardless of mutations abrogating ALIX and Gag interaction. In addition, mutations abrogating interactions between Gag and TSG101 result in recruitment of ESCRTs with a substantial delay while maintaining similar stoichiometry. Our results demonstrate that recruitment of ESCRTs is driven by a robust network of interactions resulting in an “On/Off” switch behavior and ALIX’s interactions with late domains of HIV Gag play a crucial role during final catalysis of membrane fission after assembly of the full ESCRT machinery.

Movement of Calcium Ions and their Role in the Activation of Platelets

1978 ◽  
Vol 40 (02) ◽  
pp. 212-218 ◽  
Author(s):  
P Massini ◽  
R Käser-Glanzmann ◽  
E F Lüscher
Keyword(s):  
Plasma Membrane ◽  
Platelet Activation ◽  
Calcium Ions ◽  
Binding Sites ◽  
Shape Change ◽  
Release Reaction ◽  
Dense Bodies ◽  
Activated Platelets ◽  
Different Types ◽  
Ca Ions

SummaryThe increase of the cytoplasmic Ca-concentration plays a central role in the initiation of platelet activation. Four kinds of movements of Ca-ions are presumed to occur during this process: a) Ca-ions liberated from membranes induce the rapid shape change, b) Vesicular organelles release Ca-ions into the cytoplasm which initiate the release reaction, c) The storage organelles called dense bodies, secrete their contents including Ca-ions to the outside during the release reaction, d) At the same time a rearrangement of the plasma membrane occurs, resulting in an increase in its permeability for Ca-ions as well as in an increase in the number of Ca-binding sites.Since most processes occurring during platelet activation are reversible, the platelet must be equipped with a mechanism which removes Ca-ions from the cytoplasm. A vesicular fraction obtained from homogenized platelets indeed accumulates Ca actively. This Ca- pump is stimulated by cyclic AMP and protein kinase; it may be involved in the recovery of platelets after activation.It becomes increasingly clear that the various manifestations of platelet activation are triggered by a rise in the cytoplasmic Ca2+-concentration. The evidence for this and possible mechanisms involved are discussed in some detail in the contributions by Detwiler et al. and by Gerrard and White to this symposium. In this article we shall discuss four different types of mobilization of Ca-ions which occur in the course of the activation of platelets. In addition, at least one transport step involved in the removal of Ca2+ must occur during relaxation of activated platelets.

scholarly journals Tracking the Fate of Genetically Distinct Vesicular Stomatitis Virus Matrix Proteins Highlights the Role for Late Domains in Assembly

2015 ◽  
Vol 89 (23) ◽  
pp. 11750-11760 ◽  
Author(s):  
Timothy K. Soh ◽  
Sean P. J. Whelan
Keyword(s):  
Plasma Membrane ◽  
Vesicular Stomatitis Virus ◽  
Matrix Protein ◽  
Fluorescent Proteins ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Particles ◽  
The Matrix ◽  
Vesicular Stomatitis ◽  
Late Domains

ABSTRACTVesicular stomatitis virus (VSV) assembly requires condensation of the viral ribonucleoprotein (RNP) core with the matrix protein (M) during budding from the plasma membrane. The RNP core comprises the negative-sense genomic RNA completely coated by the nucleocapsid protein (N) and associated by a phosphoprotein (P) with the large polymerase protein (L). To study the assembly of single viral particles, we tagged M and P with fluorescent proteins. We selected from a library of viruses with insertions in the M gene a replication-competent virus containing a fluorescent M and combined that with our previously described virus containing fluorescent P. Virus particles containing those fusions maintained the same bullet shape appearance as wild-type VSV but had a modest increase in particle length, reflecting the increased genome size. Imaging of the released particles revealed a variation in the amount of M and P assembled into the virions, consistent with a flexible packaging mechanism. We used the recombinants to further study the importance of the late domains in M, which serve to recruit the endosomal sorting complex required for transport (ESCRT) machinery during budding. Mutations in late domains resulted in the accumulation of virions that failed to pinch off from the plasma membrane. Imaging of single virions released from cells that were coinfected with M tagged with enhanced green fluorescent protein and M tagged with mCherry variants in which the late domains of one virus were inactivated by mutation showed a strong bias against the incorporation of the late-domain mutant into the released virions. In contrast, the intracellular expression and membrane association of the two variants were unaltered. These studies provide new tools for imaging particle assembly and enhance our resolution of existing models for assembly of VSV.IMPORTANCEAssembly of vesicular stomatitis virus (VSV) particles requires the separate trafficking of the viral replication machinery, a matrix protein (M) and a glycoprotein, to the plasma membrane. The matrix protein contains a motif termed a “late domain” that engages the host endosomal sorting complex required for transport (ESCRT) machinery to facilitate the release of viral particles. Inactivation of the late domains through mutation results in the accumulation of virions arrested at the point of release. In the study described here, we developed new tools to study VSV assembly by fusing fluorescent proteins to M and to a constituent of the replication machinery, the phosphoprotein (P). We used those tools to show that the late domains of M are required for efficient incorporation into viral particles and that the particles contain a variable quantity of M and P.

scholarly journals Povidone-Iodine Attenuates Viral Replication in Ocular Cells: Implications for Ocular Transmission of RNA Viruses

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 753
Author(s):  
Sneha Singh ◽  
Onkar B. Sawant ◽  
Shahzad I. Mian ◽  
Ashok Kumar
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Povidone Iodine ◽  
Rna Viruses ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Host Cells ◽  
Eye Banking ◽  
Antiviral Effects ◽  
Infected Cells

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1β) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.

scholarly journals Customer Segmentation Through Path Reconstruction

2020 ◽  
Author(s):  
Santiago García
Keyword(s):  
Rapid Development ◽  
Customer Segmentation ◽  
Smart Phones ◽  
Indoor Environments ◽  
Flow Conditions ◽  
Gps Receivers ◽  
Current State ◽  
Different Types

With the rapid development of smart phones, tablets and their operative systems, many positioning enabled sensors have been built into these devices. Users can now accurately fix their location according to the function of GPS receivers. For indoor environments, as in the case we are studying, WiFi based positioning is preferred to GPS due to the attenuation or obstruction of signals. This paper deals with the automatic classification of customers in a Sports Shop Center on the basis of their movements around the shop's premises. To achieve this goal, we start by collecting (x,y) coordinates from customers while they visit the store. Consequently, any costumer's path through the shop is formed by a list of coordinates, obtained with a frequency of one measurement per minute. Then, a guess about the full trajectory is constructed and a number of parameters about these trajectories is calculated before performing an Unsupervised Learning Clustering Process. As a result, we can identify several types of customers, and the dynamics of their behavior inside the shop. This information is of great value to the company, to be used both in the long term and also in short periods of time, monitoring the current state of the shop at any moment, identifying different types of situation appearing during restricted periods, or predicting customer flow conditions

scholarly journals Understanding the Urgent Need for Subtitling for the Deaf and Hard of Hearing in the Spanish-Speaking Greater Antilles

2020 ◽  
Vol 3 (2) ◽  
Author(s):  
Adrián Fuentes-Luque ◽  
Pabsi Livmar González-Irizarry
Keyword(s):  
Puerto Rico ◽  
Dominican Republic ◽  
Hard Of Hearing ◽  
Greater Antilles ◽  
Social Barriers ◽  
Spanish Speaking ◽  
Current State ◽  
The World ◽  
Different Types ◽  
The Caribbean

Even though Audiovisual Translation (AVT) is growing and flourishing throughout the world, it is practically unheard-of in the Caribbean, where accessibility faces an even bleaker existence. The circumstances of the deaf and hard of hearing (also referred to as D/deaf) are no less alarming: social barriers and exclusion are widespread. This paper emphasizes the need to make subtitles accessible in the Spanish-speaking Caribbean, specifically on the islands of Puerto Rico, Cuba, and the Dominican Republic, and underscores the challenges faced by the D/deaf communities on each island. Our research focuses on issues like AVT laws and regulations, the habits of viewers of audiovisual (AV) products, and literacy and limitations on each island. This paper also examines the different types of D/deaf audiovisual consumers in the Spanish-speaking Caribbean and the difficulties each community faces when accessing media and entertainment. Our research reveals the current state of AVT accessibility in this region and provides a foundation for influencing legislators to begin enforcing AVT regulations and drafting SDH guidelines.

scholarly journals Noise-induced bistability in the quasineutral coexistence of viral RNA under different replication modes

2018 ◽  
Author(s):  
Josep Sardanyés ◽  
Andreu Arderiu ◽  
Santiago F. Elena ◽  
Tomás Alarcón
Keyword(s):  
Viral Replication ◽  
Evolutionary Dynamics ◽  
Rna Viruses ◽  
Initial Conditions ◽  
Rna Replication ◽  
Viral Rna ◽  
Stochastic Simulations ◽  
Strong Impact ◽  
Deterministic Models ◽  
The Impact

Evolutionary and dynamical investigations on real viral populations indicate that RNA replication can range between two extremes given by so-called stamping machine replication (SMR) and geometric replication (GR). The impact of asymmetries in replication for single-stranded, (+) sense RNA viruses has been up to now studied with deterministic models. However, viral replication should be better described by including stochasticity, since the cell infection process is typically initiated with a very small number of RNA macromolecules, and thus largely influenced by intrinsic noise. Under appropriate conditions, deterministic theoretical descriptions of viral RNA replication predict a quasineutral coexistence scenario, with a line of fixed points involving different strands’ equilibrium ratios depending on the initial conditions. Recent research on the quasineutral coexistence in two competing populations reveals that stochastic fluctuations fundamentally alters the mean-field scenario, and one of the two species outcompetes the other one. In this manuscript we study this phenomenon for RNA viral replication modes by means of stochastic simulations and a diffusion approximation. Our results reveal that noise has a strong impact on the amplification of viral RNA, also causing the emergence of noise-induced bistability. We provide analytical criteria for the dominance of (+) sense strands depending on the initial populations on the line of equilibria, which are in agreement with direct stochastic simulation results. The biological implications of this noise-driven mechanism are discussed within the framework of the evolutionary dynamics of RNA viruses with different modes of replication.

scholarly journals Late activation of theRaf/MEK/ERKpathway is required for translocation of the respiratory syncytial virusFprotein to the plasma membrane and efficient viral replication

2018 ◽  
Vol 21 (1) ◽  
pp. e12955 ◽  
Author(s):  
Hannah F. Preugschas ◽  
Eike R. Hrincius ◽  
Carolin Mewis ◽  
Giao V.Q. Tran ◽  
Stephan Ludwig ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Viral Replication ◽  
Efficient Viral Replication
Sign in / Sign up

Export Citation Format

Share Document