scholarly journals How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

2021 ◽  
Author(s):  
Nabil G Seidah ◽  
Antonella Pasquato ◽  
Ursula Andreo
Keyword(s):  
Plasma Membranes ◽  
Viral Infections ◽  
Limited Proteolysis ◽  
Viral Envelope ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Type I ◽  
Proprotein Convertases ◽  
Enveloped Viruses ◽  
Surface Glycoproteins

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusiogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

scholarly journals How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1229
Author(s):  
Nabil G. Seidah ◽  
Antonella Pasquato ◽  
Ursula Andréo
Keyword(s):  
Plasma Membranes ◽  
Viral Infections ◽  
Limited Proteolysis ◽  
Viral Envelope ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Type I ◽  
Proprotein Convertases ◽  
Enveloped Viruses ◽  
Surface Glycoproteins

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires the fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P, and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections, such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

scholarly journals The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses

2016 ◽  
Vol 90 (19) ◽  
pp. 8780-8794 ◽  
Author(s):  
Subhajit Poddar ◽  
Jennifer L. Hyde ◽  
Matthew J. Gorman ◽  
Michael Farzan ◽  
Michael S. Diamond
Keyword(s):  
Viral Infections ◽  
Transmembrane Protein ◽  
Flow Cytometric Analysis ◽  
Antiviral Effect ◽  
Host Cells ◽  
Type I ◽  
Targeted Gene Deletion ◽  
Multiple Organs ◽  
Viral Burden ◽  
Alphavirus Infection

ABSTRACTHost cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased inIfitm3−/−andIfitmlocus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,Ifitm3−/−mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested thatIfitm3−/−macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments withIfitm3−/−bone marrow-derived macrophages.Ifitm3−/−mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.IMPORTANCEThe interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion ofIfitm3as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

scholarly journals Exploring lectin–glycan interactions to combat COVID-19: Lessons acquired from other enveloped viruses

Glycobiology ◽  
2020 ◽  
Author(s):  
Luís Cláudio Nascimento da Silva ◽  
Juliana Silva Pereira Mendonça ◽  
Weslley Felix de Oliveira ◽  
Karla Lílian Rodrigues Batista ◽  
Adrielle Zagmignan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Whole Blood ◽  
Therapeutic Approach ◽  
Viral Infections ◽  
Viral Envelope ◽  
Structural Studies ◽  
Human Coronavirus ◽  
Enveloped Viruses ◽  
Wide Range ◽  
Great Pressure

Abstract The emergence of a new human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed great pressure on the health system worldwide. The presence of glycoproteins on the viral envelope opens a wide range of possibilities for the application of lectins to address some urgent problems involved in this pandemic. In this work, we discuss the potential contributions of lectins from nonmammalian sources in the development of several fields associated with viral infections, most notably COVID-19. We review the literature on the use of nonmammalian lectins as a therapeutic approach against members of the Coronaviridae family, including recent advances in strategies of protein engineering to improve their efficacy. The applications of lectins as adjuvants for antiviral vaccines are also discussed. Finally, we present some emerging strategies employing lectins for the development of biosensors, microarrays, immunoassays and tools for purification of viruses from whole blood. Altogether, the data compiled in this review highlight the importance of structural studies aiming to improve our knowledge about the basis of glycan recognition by lectins and its repercussions in several fields, providing potential solutions for complex aspects that are emerging from different health challenges.

scholarly journals Collision between Two Pandemics: Obesity and COVID-19 Viral Infection

2021 ◽  
pp. 27-37
Author(s):  
Jehan Saad Alrahimi
Keyword(s):  
Immune System ◽  
Chronic Inflammation ◽  
Complex Disease ◽  
Viral Infections ◽  
Host Cells ◽  
Organ Injury ◽  
Primary Immune Response ◽  
Type I ◽  
Novel Coronavirus ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (COVID-19). The principal risk factor for the development of serious forms of COVID-19 was found to be the precarious metabolic health. There are several mechanisms that are implicated in the seriousness of COVID-19 ranging from attenuation of immune system function to chronic inflammation. It is important to keep in mind that obesity is a complex disease when discussing the relation between obesity and the severity of COVID-19. An increasing body of proof links obesity to COVID-19. Obesity has an obvious role in the high incidence, symptoms severity and mortality rates of viral infections seen in obese patients. Adipose tissue shows a high expression of the angiotensin-converting enzyme 2 (ACE2), the receptor for entry of SARS-CoV-2 into host cells, so obese population exhibit higher vulnerability to COVID-19. The primary immune response is offered mainly by type-I interferon (IFN-I) that is suppressed in COVID-19. The pro-inflammatory state associated with obesity produces imbalance of the inflammatory response to COVID-19, as the cytokine storm found in subjects with serious disease form. Obesity is considered as chronic inflammation of low degree, so it shows a capacity for pathogenic immune amplification. In this review, the effect of obesity on the immune system is described. The authors described the dysfunctional immune responses caused by obesity that lead to organ injury in COVID-19 infection and impair the ability of patient to combat the virus. Further research is required to assess the impact of obesity control, immunonutrition and physical exercise in SARS-CoV-2 infection.

The variations of virus shape and size in different preparations

1990 ◽  
Vol 48 (3) ◽  
pp. 580-581
Author(s):  
Ding Mingxiao ◽  
Jiao Renjie ◽  
Liang Fengxia ◽  
Zhai Zhonghe
Keyword(s):  
Sindbis Virus ◽  
Viral Envelope ◽  
Host Cells ◽  
Enveloped Viruses ◽  
Viral Attachment ◽  
Cytopathic Effects ◽  
Surface Replica ◽  
Freeze Etching ◽  
Vesicular Stomatitis ◽  
Important Structure

Envelope is a very important structure for viral attachment and entry into the host cell, but it is also a morphologically variable portion of enveloped viruses. Studying the fine structure of enveloped viruses, we noticed that different sample preparations of viruses resulted in the change of viral size and shape to some extent, which we believe was caused by the variation of the viral envelope. Four typical enveloped viruses: IBRV (Infectious Bovine Rhinotracheitis Virus), GPV (Goat Pox Virus), SbV (Sindbis Virus) and VSV (Vesicular Stomatitis Virus) were investigated in our experiments.Host cells infected with IBRV, GPV, SbV and VSV respectively were fixed with 1-5% glutaraldehyde in Hank's buffer when the cytopathic effects appeared in 50-70% of the cells, then the specimens were treated respectively with different conventional methods of EM sample preparation: 1) ultrathin sectioning, 2) negative staining,3) freeze etching, 4) surface replica, 5) whole mount or SEM observations. All the samples were examined under JEM-200CX TEM or JSM-35CF SEM.

scholarly journals Arms Race between Enveloped Viruses and the Host ERAD Machinery

2016 ◽  
Author(s):  
Dylan A. Frabutt ◽  
Yong-Hui Zheng
Keyword(s):  
Cellular Localization ◽  
Viral Envelope ◽  
Host Cells ◽  
Envelope Glycoproteins ◽  
Viral Fusion ◽  
Enveloped Viruses ◽  
Protein Levels ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

scholarly journals THERAPEUTIC APPLICATIONS OF Spirulina AGAINST HUMAN PATHOGENIC VIRUSES

2021 ◽  
Vol 9 (Spl-1- GCSGD_2020) ◽  
pp. S38-S42
Author(s):  
Sharolynne Xiao Tong Liang ◽  
◽  
Ling Shing Wong ◽  
Anto Cordelia Tanislaus Antony Dhanapal ◽  
Prakash Balu ◽  
...  
Keyword(s):  
Measles Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Emerging Infectious Diseases ◽  
Antiviral Effect ◽  
Food Supplement ◽  
Host Cells ◽  
Swine Flu ◽  
Virus Infections ◽  
Enveloped Viruses

Viruses can spread worldwide and the early detection of emerging infectious diseases and outbreaks in humans and animals is important for effective surveillance and prevention. Viruses such as human immunodeficiency virus (HIV), swine flu, and influenza virus are some of the viruses that spread diseases worldwide. However, the non-availability of effective antiviral drugs and the drug-resistance among the virus and host have become the major problems in controlling viral infections. The natural products from microalgae can be an alternative therapeutic agent to control viral infections in humans. Spirulina is a well-known cyanobacterium that has been consumed by humans as a food supplement for more than centuries without side-effects. Spirulina possesses high nutritional values and provides numerous health benefits to the consumers. Spirulina can be an alternative natural therapeutic agent for numerous virus infections as it contains several bioactive compounds with proven antiviral effect on enveloped viruses (Herpes simplex virus, measles virus, mumps virus) and non-enveloped viruses (astrovirus, rotavirus) by preventing the spread of the virus in the host cells. Spirulina also serves as a natural supplement that strengthens the immune system. This review focuses on the antiviral properties and immunostimulant effects of Spirulina as a potential therapeutic supplement on human health.

Viral Envelope Membrane: A Special Entry Pathway and a Promising Drug Target

2021 ◽  
Vol 28 ◽  
Author(s):  
Nastasja Palombi ◽  
Annalaura Brai ◽  
Martina Gerace ◽  
Salvatore Di Maria ◽  
Francesco Orofino ◽  
...  
Keyword(s):  
Drug Target ◽  
Viral Infections ◽  
Viral Envelope ◽  
Envelope Membrane ◽  
Virus Infections ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Entry Pathway ◽  
Current Century ◽  
Spanish Flu

Abstract: Enveloped viruses belong to a large class of pathogens responsible for multiple serious diseases. Their spread into new territories has been the cause of major epidemics throughout human history, including the Spanish flu in 1918 and the latest COVID-19 pandemic. Thanks to their outer membrane, consisting essentially of host lipids, enveloped viruses are more resistant to enzymes, and are also less susceptible to host immune defenses than their naked counterparts. Therefore, the development of effective approaches to combat enveloped virus infections represents a major challenge for antiviral therapy in the current century. This review focuses on the characteristics of enveloped viruses, their importance in the entry phase, drugs targeting envelope membrane-mediated entry, and those specifically designed to target the envelope. The broad-spectrum antiviral activity of these compounds can be attributed to their ability to affect the envelope, an essential structural feature common to several viruses. This makes this class of compounds agents of great interest when no specific drugs or vaccines are available to block viral infections.

scholarly journals One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS-CoV-2

2021 ◽  
Author(s):  
Mariana F. Tioni ◽  
Robert Jordan ◽  
Angie Silva Pena ◽  
Aditya Garg ◽  
Danlu Wu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rna Virus ◽  
Low Cost ◽  
Viral Envelope ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Viral Envelope Protein ◽  
Phase I Clinical Trials ◽  
Global Pandemic ◽  
Syncytial Virus

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. Vaccines are needed to control the disease and bring an end to the pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing the peak shedding of SARS-CoV-2 in the nose by more than 200-fold. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase I clinical trials as a single-dose intranasal COVID-19 vaccine.

Functional Domains within Fusion Proteins: Prospectives for Development of Peptide Inhibitors of Viral Cell Fusion

2000 ◽  
Vol 20 (6) ◽  
pp. 535-555 ◽  
Author(s):  
Yechiel Shai
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Peptide Inhibitors ◽  
Viral Envelope ◽  
Host Cells ◽  
Functional Domains ◽  
Fusion Event ◽  
Enveloped Viruses ◽  
Target Plasma ◽  
Shed Light

The entry of enveloped viruses into host cells is accomplished by fusion ofthe viral envelope and target plasma membrane and is mediated by fusionproteins. Recently, several functional domains within fusion proteins fromdifferent viral families were identified. Some are directly involved inconformational changes after receptor binding, as suggested by the recentrelease of crystallographically determined structures of a highly stablecore structure of the fusion proteins in the absence of membranes. However, in the presence of membranes, this core binds strongly to the membrane's surface and dissociates therein. Other regions, besides the N-terminal fusionpeptide, which include the core region and an internal fusion peptide inparamyxoviruses, are directly involved in the actual membrane fusion event, suggesting an “umbrella” like model for the membrane inducedconformational change of fusion proteins. Peptides resembling these regionshave been shown to have specific antiviral activity, presumably because theyinterfere with the corresponding domains within the viruses. Overall, thesestudies shed light into the molecular mechanism of membrane fusion induced byenvelope glycoproteins and suggest that fusion proteins from different viralfamilies share common structural and functional motifs.

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