scholarly journals The Role of Viral Proteins in the Regulation of Exosomes Biogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaonan Jia ◽  
Yiqian Yin ◽  
Yiwen Chen ◽  
Lingxiang Mao
Keyword(s):  
Nucleic Acids ◽  
Viral Infection ◽  
Viral Proteins ◽  
Viral Genomes ◽  
Extracellular Milieu ◽  
Membrane Bound ◽  
Viral Components ◽  
External Stimuli

Exosomes are membrane-bound vesicles of endocytic origin, secreted into the extracellular milieu, in which various biological components such as proteins, nucleic acids, and lipids reside. A variety of external stimuli can regulate the formation and secretion of exosomes, including viruses. Viruses have evolved clever strategies to establish effective infections by employing exosomes to cloak their viral genomes and gain entry into uninfected cells. While most recent exosomal studies have focused on clarifying the effect of these bioactive vesicles on viral infection, the mechanisms by which the virus regulates exosomes are still unclear and deserve further attention. This article is devoted to studying how viral components regulate exosomes biogenesis, composition, and secretion.

scholarly journals Inducible microRNA-590-5p inhibits host antiviral response by targeting the soluble interleukin-6 (IL6) receptor

2018 ◽  
Vol 293 (47) ◽  
pp. 18168-18179 ◽  
Author(s):  
Yaqin Zhou ◽  
Zhangchuan Xia ◽  
Zhikui Cheng ◽  
Gang Xu ◽  
Xiaodan Yang ◽  
...  
Keyword(s):  
Viral Infection ◽  
Interleukin 6 ◽  
Underlying Mechanism ◽  
Antiviral Response ◽  
Type I ◽  
Interleukin 6 Receptor ◽  
Important Regulator ◽  
Membrane Bound ◽  
Host Antiviral Response

MicroRNA (miR)-590-5p has been identified as an important regulator of some signaling pathways such as cell proliferation and tumorigenesis. However, little is known about its role during viral infection. Here, we report that miR-590-5p was significantly induced by various viruses and effectively potentiated virus replication in different viral infection systems. Furthermore, miR-590-5p substantially attenuated the virus-induced expression of type I and type III interferons (IFNs) and inflammatory cytokines, resulting in impaired downstream antiviral signaling. Interleukin-6 receptor (IL6R) was identified as a target of miR-590-5p. Interestingly, the role of miR-590-5p in virus-triggered signaling was abolished in IL6R knockout cells, and this could be rescued by restoring the expression of the soluble IL6R (sIL6R) but not the membrane-bound IL6R (mIL6R), suggesting that sIL6R is indispensable for miR-590-5p in modulating the host antiviral response. Furthermore, miR-590-5p down-regulated endogenous sIL6R and mIL6R expression through a translational repression mechanism. These findings thus uncover a previously uncharacterized role and the underlying mechanism of miR-590-5p in the innate immune response to viral infection.

scholarly journals Hsp70 Negatively Controls Rotavirus Protein Bioavailability in Caco-2 Cells Infected by the Rotavirus RF Strain

2006 ◽  
Vol 81 (3) ◽  
pp. 1297-1304 ◽  
Author(s):  
Alexis H. Broquet ◽  
Christelle Lenoir ◽  
Agnès Gardet ◽  
Catherine Sapin ◽  
Serge Chwetzoff ◽  
...  
Keyword(s):  
Viral Infection ◽  
Proteasome Inhibitors ◽  
Virus Production ◽  
Viral Proteins ◽  
Host Cells ◽  
Progeny Virus ◽  
Virus Protein ◽  
Interfering Rna ◽  
Hsp70 Induction

ABSTRACT Previous studies demonstrated that the induction of the heat shock protein Hsp70 in response to viral infection is highly specific and differs from one cell to another and for a given virus type. However, no clear consensus exists so far to explain the likely reasons for Hsp70 induction within host cells during viral infection. We show here that upon rotavirus infection of intestinal cells, Hsp70 is indeed rapidly, specifically, and transiently induced. Using small interfering RNA-Hsp70-transfected Caco-2 cells, we observed that Hsp70 silencing was associated with an increased virus protein level and enhanced progeny virus production. Upon Hsp70 silencing, we observed that the ubiquitination of the main rotavirus structural proteins was strongly reduced. In addition, the use of proteasome inhibitors in infected Caco-2 cells was shown to induce an accumulation of structural viral proteins. Together, these results are consistent with a role of Hsp70 in the control of the bioavailability of viral proteins within cells for virus morphogenesis.

scholarly journals RNA Silencing May Play a Role in but Is Not the Only Determinant of the Multiplicity of Infection

2015 ◽  
Vol 90 (1) ◽  
pp. 553-561 ◽  
Author(s):  
Livia Donaire ◽  
József Burgyán ◽  
Fernando García-Arenal
Keyword(s):  
Gene Silencing ◽  
Viral Proteins ◽  
Virus Evolution ◽  
Multiplicity Of Infection ◽  
Silencing Suppressor ◽  
Content Type ◽  
Viral Genomes ◽  
A Cell ◽  
Virus Fitness

ABSTRACTThe multiplicity of infection (MOI), i.e., the number of viral genomes that infect a cell, is an important parameter in virus evolution, which for each virus and environment may have an optimum value that maximizes virus fitness. Thus, the MOI might be controlled by virus functions, an underexplored hypothesis in eukaryote-infecting viruses. To analyze if the MOI is controlled by virus functions, we estimated the MOI in plants coinfected by two genetic variants ofTomato bushy stunt virus(TBSV); by TBSV and a TBSV-derived defective interfering RNA (DI-RNA); or by TBSV and a second tombusvirus,Cymbidium ringspot virus(CymRSV). The MOI was significantly larger in TBSV-CymRSV coinfections (∼4.0) than in TBSV-TBSV or TBSV–DI-RNA coinfections (∼1.7 to 2.2). Coinfections by CymRSV or TBSV with chimeras in which an open reading frame (ORF) of one virus species was replaced by that of the other identified a role of viral proteins in determining the MOI, which ranged from 1.6 to 3.9 depending on the coinfecting genotypes. However, no virus-encoded protein or genomic region was the sole MOI determinant. Coinfections by CymRSV and TBSV mutants in which the expression of the gene-silencing suppressor protein p19 was abolished also showed a possible role of gene silencing in MOI determination. Taken together, these results demonstrate that the MOI is a quantitative trait showing continuous variation and that as such it has a complex determination involving different virus-encoded functions.IMPORTANCEThe number of viral genomes infecting a cell, or the multiplicity of infection (MOI), is an important parameter in virus evolution affecting recombination rates, selection intensity on viral genes, evolution of multipartite genomes, or hyperparasitism by satellites or defective interfering particles. For each virus and environment, the MOI may have an optimum value that maximizes virus fitness, but little is known about MOI control in eukaryote-infecting viruses. We show here that in plants coinfected by two genotypes ofTomato bushy stunt virus(TBSV), the MOI was lower than in plants coinfected by TBSV andCymbidium ringspot virus(CymRSV). Coinfections by CymRSV or TBSV with TBSV-CymRSV chimeras showed a role of viral proteins in MOI determination. Coinfections by CymRSV and TBSV mutants not expressing the gene-silencing suppressor protein also showed a role of gene silencing in MOI determination. The results demonstrate that the MOI is a quantitative trait with a complex determination involving different viral functions.

scholarly journals The Viral Polymerase Complex Mediates the Interaction of vRNPs with Recycling Endosomes During SeV Assembly

2020 ◽  
Author(s):  
Emmanuelle Genoyer ◽  
Katarzyna Kulej ◽  
Chuan Tien Hung ◽  
Patricia A. Thibault ◽  
Kristopher Azarm ◽  
...  
Keyword(s):  
Sendai Virus ◽  
Initial Step ◽  
Viral Proteins ◽  
Viral Polymerase ◽  
Recycling Endosomes ◽  
Viral Genomes ◽  
Parainfluenza Viruses ◽  
Infected Cells ◽  
Human Parainfluenza Viruses

ABSTRACTParamyxoviruses are negative sense single-stranded RNA viruses that comprise many important human and animal pathogens, including human parainfluenza viruses. These viruses bud from the plasma membrane of infected cells after the viral ribonucleoprotein complex (vRNP) is transported from the cytoplasm to the cell membrane via Rab11a-marked recycling endosomes. The viral proteins that are critical for mediating this important initial step in viral assembly are unknown. Here we use the model paramyxovirus, murine parainfluenza virus 1, or Sendai virus (SeV), to investigate the roles of viral proteins in Rab11a-driven virion assembly. We previously reported that infection with SeV containing high levels of copy-back defective viral genomes (DVGs) generates heterogenous populations of cells. Cells enriched in full-length virus produce viral particles containing standard or defective viral genomes, while cells enriched in DVGs do not, despite high levels of defective viral genome replication. Here we take advantage of this heterogenous cell phenotype to identify proteins that mediate interaction of vRNPs with Rab11a. We examine the role of matrix protein and nucleoprotein and determine that they are not sufficient to drive interaction of vRNPs with recycling endosomes. Using a combination of mass spectrometry and comparative protein abundance and localization in DVG- and FL-high cells, we identify viral polymerase complex components L and, specifically, its cofactor C proteins as interactors with Rab11a. We find that accumulation of these proteins within the cell is the defining feature that differentiates cells that proceed to viral egress from cells which remain in replication phases.IMPORTANCEParamyxoviruses are a family of viruses that include a number of pathogens with significant burdens on human health. Particularly, human parainfluenza viruses are an important cause of pneumonia and bronchiolitis in children for which there are no vaccines or direct acting antivirals. These cytoplasmic replicating viruses bud from the plasma membrane and coopt cellular endosomal recycling pathways to traffic viral ribonucleoprotein complexes from the cytoplasm to the membrane of infected cells. The viral proteins required for viral engagement with the recycling endosome pathway are still not known. Here we use the model paramyxovirus Sendai virus, or murine parainfluenza virus 1, to investigate the role of viral proteins in this initial step of viral assembly. We find that viral polymerase components large protein L and accessory C proteins are necessary for engagement with recycling endosomes. These findings are important in identifying viral proteins as potential targets for development of antivirals.

IP3R, store-operated Ca2+ entry and neuronal Ca2+ homoeostasis in Drosophila

2012 ◽  
Vol 40 (1) ◽  
pp. 279-281 ◽  
Author(s):  
Sumita Chakraborty ◽  
Gaiti Hasan
Keyword(s):  
Endoplasmic Reticulum ◽  
G Protein Coupled Receptors ◽  
Neuronal Function ◽  
Extracellular Milieu ◽  
Inositol 1,4,5 Trisphosphate ◽  
Membrane Bound ◽  
Trisphosphate Receptor ◽  
Neuronal Physiology ◽  
G Protein Coupled

The IP3R (inositol 1,4,5-trisphosphate receptor) releases Ca2+ from the ER (endoplasmic reticulum) store upon binding to its ligand InsP3, which is thought to be generated by activation of certain membrane-bound G-protein-coupled receptors in Drosophila. Depletion of Ca2+ in the ER store also activates SOCE (store-operated Ca2+ entry) from the extracellular milieu across the plasma membrane, leading to a second rise in cytosolic Ca2+, which is then pumped back into the ER. The role of the IP3R and SOCE in mediating Ca2+ homoeostasis in neurons, their requirement in neuronal function and effect on neuronal physiology and as a consequence behaviour, are reviewed in the present article.

scholarly journals Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1597
Author(s):  
Olga V. Iarovaia ◽  
Elena S. Ioudinkova ◽  
Artem K. Velichko ◽  
Sergey V. Razin
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Viral Infection ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Infection Process ◽  
Regulatory Pathways ◽  
Nucleolar Proteins

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.

scholarly journals Combinatorial interactions between viral proteins expand the functional landscape of the viral proteome

2021 ◽  
Author(s):  
Liping Wang ◽  
Huang Tan ◽  
Laura Medina-Puche ◽  
Mengshi Wu ◽  
Borja Garnelo Gomez ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Host Cells ◽  
In Planta ◽  
Viral Genomes ◽  
Intracellular Parasites ◽  
Molecular Machinery ◽  
Combinatorial Interactions ◽  
Massive Cell ◽  
Coding Capacity

As intracellular parasites, viruses need to manipulate the molecular machinery of their host cells in order to enable their own replication and spread. This manipulation is based on the activity of virus-encoded proteins. The reduced size of viral genomes imposes restrictions in coding capacity; how the action of the limited number of viral proteins results in the massive cell reprogramming observed during the viral infection is a long-standing conundrum in virology. In this work, we explore the hypothesis that combinatorial interactions expand the multifunctionality of viral proteins, which may exert different activities individually and when in combination, physical or functional. We show that the proteins encoded by a plant-infecting DNA virus physically associate with one another in an intricate network. Our results further demonstrate that these interactions can modify the subcellular localization of the viral proteins involved, and that co-expressed interacting viral proteins can exert novel biological functions in planta that go beyond the sum of their individual functions. Based on this, we propose a model in which combinatorial physical and functional interactions between viral proteins enlarge the functional landscape of the viral proteome, which underscores the importance of studying the role of viral proteins in the context of the infection.

scholarly journals A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1405
Author(s):  
Mabroka H. Saad ◽  
Raied Badierah ◽  
Elrashdy M. Redwan ◽  
Esmail M. El-Fakharany
Keyword(s):  
Viral Infection ◽  
Immune Modulation ◽  
Viral Infections ◽  
Biologically Active ◽  
Viral Propagation ◽  
Cellular Factors ◽  
Pathogenic Viruses ◽  
Downstream Processes ◽  
Viral Components

Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with a variety of cellular molecules, including RNAs, proteins, and lipids. However, it has been found to play a crucial role in several biological processes such as immune modulation, cellular communication, and their role as vehicles to transport biologically active molecules. The latest discoveries have revealed that many viruses export their viral elements within cellular factors using exosomes. Hijacking the exosomal pathway by viruses influences downstream processes such as viral propagation and cellular immunity and modulates the cellular microenvironment. In this manuscript, we reviewed exosomes biogenesis and their role in the immune response to viral infection. In addition, we provided a summary of how some pathogenic viruses hijacked this normal physiological process. Viral components are harbored in exosomes and the role of these exosomes in viral infection is discussed. Understanding the nature of exosomes and their role in viral infections is fundamental for future development for them to be used as a vaccine or as a non-classical therapeutic strategy to control several viral infections.

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