scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals The ATP-Dependent RNA Helicase DDX3X Modulates Herpes Simplex Virus 1 Gene Expression

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Bita Khadivjam ◽  
Camille Stegen ◽  
Marc-Aurèle Hogue-Racine ◽  
Nabil El Bilali ◽  
Katinka Döhner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex ◽  
Rna Viruses ◽  
Rna Helicase ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Dna Viruses ◽  
Viral Particles ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The human protein DDX3X is a DEAD box ATP-dependent RNA helicase that regulates transcription, mRNA maturation, and mRNA export and translation. DDX3X concomitantly modulates the replication of several RNA viruses and promotes innate immunity. We previously showed that herpes simplex virus 1 (HSV-1), a human DNA virus, incorporates DDX3X into its mature particles and that DDX3X is required for optimal HSV-1 infectivity. Here, we show that viral gene expression, replication, and propagation depend on optimal DDX3X protein levels. Surprisingly, DDX3X from incoming viral particles was not required for the early stages of the HSV-1 infection, but, rather, the protein controlled the assembly of new viral particles. This was independent of the previously reported ability of DDX3X to stimulate interferon type I production. Instead, both the lack and overexpression of DDX3X disturbed viral gene transcription and thus subsequent genome replication. This suggests that in addition to its effect on RNA viruses, DDX3X impacts DNA viruses such as HSV-1 by an interferon-independent pathway. IMPORTANCE Viruses interact with a variety of cellular proteins to complete their life cycle. Among them is DDX3X, an RNA helicase that participates in most aspects of RNA biology, including transcription, splicing, nuclear export, and translation. Several RNA viruses and a limited number of DNA viruses are known to manipulate DDX3X for their own benefit. In contrast, DDX3X is also known to promote interferon production to limit viral propagation. Here, we show that DDX3X, which we previously identified in mature HSV-1 virions, stimulates HSV-1 gene expression and, consequently, virion assembly by a process that is independent of its ability to promote the interferon pathway.

scholarly journals Extracellular Vesicles Released by Leishmania: Impact on Disease Development and Immune System Cells

2021 ◽  
Author(s):  
Rogéria Cristina Zauli ◽  
Andrey Sladkevicius Vidal ◽  
Talita Vieira Dupin ◽  
Aline Correia Costa de Morais ◽  
Wagner Luiz Batista ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Immune Cells ◽  
Diagnostic Tool ◽  
Experimental Models ◽  
Host Cells ◽  
Disease Development ◽  
Leishmania Spp

Leishmania spp. release extracellular vesicles (EVs) containing parasite molecules, including several antigens and virulence factors. These EVs can interact with the host cells, such as immune cells, contributing to the parasite–host relationship. Studies have demonstrated that Leishmania-EVs can promote infection in experimental models and modulate the immune response. Although the immunomodulatory effect has been demonstrated, Leishmania-EVs can deliver parasite antigens and therefore have the potential for use as a new diagnostic tool and development of new therapeutic and vaccine approaches. This review aims to bring significant advances in the field of extracellular vesicles and Leishmania, focusing on their role in the cells of the immune system.

An Overview of Immune Evasion Strategies of DNA and RNA Viruses

2021 ◽  
Vol 21 ◽  
Author(s):  
Sheikh Saba Naz ◽  
Afsheen Aslam ◽  
Taqdees Malik
Keyword(s):  
Immune System ◽  
Rna Viruses ◽  
Adaptor Proteins ◽  
Genomic Diversity ◽  
Host Immune System ◽  
Granule Formation ◽  
Dna Viruses ◽  
Defense Proteins ◽  
Dna And Rna ◽  
Cytokines And Chemokines

A successful viral infection is due to the effective evasion of viruses from the immune system. The entry of viruses is usually detected by different cellular receptors including PRRs. Recognition of the viral genome leads to the production of interferons through a signaling stream. This review article will give brief information about escaping mechanisms of DNA and RNA viruses from the host immune system. Glimpses of these strategies include viral endonuclease activity, cap snatching of host mRNA, the formation of replication organelles, stress granule formation, membrane modifications, action of proteases, and evasion from ISGs. Moreover, we will discuss the strategies of DNA viruses to inhibit immune responses include Subversion of mRNA, transcriptional factors, Adaptor proteins, PRRs, evasion from T lymphocytes, Genomic Diversity, Theft or seize of host defense proteins, Imitation of host factors like affecting cytokines and chemokines of the host, and suppression or inhibition of apoptosis, Proteasomal degradation of host antiviral proteins by DNA Viruses. This knowledge is pivotal in understanding of different methodologies that viruses have created to escape antiviral cellular reactions of the host as well as an understanding of virus-host interactions and the origin of viral pathogenesis. Also, this knowledge is significant for the design of gene targeting vectors, antiviral vaccines, and the development of effective treatments directed against DNA and RNA viruses.

scholarly journals RNA viruses and microRNAs: challenging discoveries for the 21st century

2013 ◽  
Vol 45 (22) ◽  
pp. 1035-1048 ◽  
Author(s):  
Gokul Swaminathan ◽  
Julio Martin-Garcia ◽  
Sonia Navas-Martin
Keyword(s):  
Immune Responses ◽  
Rna Viruses ◽  
Cellular Protein ◽  
Host Cells ◽  
Dna Viruses ◽  
The Past ◽  
Complex Interactions ◽  
Viral Interactions ◽  
Cellular Machinery ◽  
Productive Replication

RNA viruses represent the predominant cause of many clinically relevant viral diseases in humans. Among several evolutionary advantages acquired by RNA viruses, the ability to usurp host cellular machinery and evade antiviral immune responses is imperative. During the past decade, RNA interference mechanisms, especially microRNA (miRNA)-mediated regulation of cellular protein expression, have revolutionized our understanding of host-viral interactions. Although it is well established that several DNA viruses express miRNAs that play crucial roles in their pathogenesis, expression of miRNAs by RNA viruses remains controversial. However, modulation of the miRNA machinery by RNA viruses may confer multiple benefits for enhanced viral replication and survival in host cells. In this review, we discuss the current literature on RNA viruses that may encode miRNAs and the varied advantages of engineering RNA viruses to express miRNAs as potential vectors for gene therapy. In addition, we review how different families of RNA viruses can alter miRNA machinery for productive replication, evasion of antiviral immune responses, and prolonged survival. We underscore the need to further explore the complex interactions of RNA viruses with host miRNAs to augment our understanding of host-virus interplay.

scholarly journals Induction and Suppression of NF-κB Signalling by a DNA Virus ofDrosophila

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
William H. Palmer ◽  
Joep Joosten ◽  
Gijs J. Overheul ◽  
Pascal W. Jansen ◽  
Michiel Vermeulen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Immune System ◽  
Rna Interference ◽  
Virus Infection ◽  
Rna Viruses ◽  
Antiviral Immunity ◽  
Toll Pathway ◽  
Dna Virus ◽  
Dna Viruses ◽  
Content Type

ABSTRACTInteractions between the insect immune system and RNA viruses have been extensively studied inDrosophila, in which RNA interference, NF-κB, and JAK-STAT pathways underlie antiviral immunity. In response to RNA interference, insect viruses have convergently evolved suppressors of this pathway that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because fewDrosophila-infecting DNA virus isolates are available. In this study, we used a recently isolated DNA virus ofDrosophila melanogaster, Kallithea virus (KV; familyNudiviridae), to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We found that fly mutants for RNA interference and immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identified the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, suggesting that Toll mediates antiviral defense against Kallithea virus infection but that it is suppressed by the virus. We found that Kallithea virus gp83 inhibits Toll signalling through the regulation of NF-κB transcription factors. Furthermore, we found that gp83 of the closely related Drosophila innubila nudivirus (DiNV) suppressesD. melanogasterToll signalling, suggesting an evolutionarily conserved function of Toll in defense against DNA viruses. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in aDrosophilavirus, extending the known diversity of insect virus-encoded immune inhibitors.IMPORTANCECoevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied inDrosophila melanogaster, primarily during RNA, but not DNA, virus infection. Therefore, we describe interactions between a recently isolatedDrosophilaDNA virus (Kallithea virus [KV]) and immune processes known to control RNA viruses, such as RNA interference (RNAi) and Imd pathways. We found that KV suppresses the Toll pathway and identified gp83 as a KV-encoded protein that underlies this suppression. This immunosuppressive ability is conserved in another nudivirus, suggesting that the Toll pathway has conserved antiviral activity against DNA nudiviruses, which have evolved suppressors in response. Together, these results indicate that DNA viruses induce and suppress NF-κB responses, and they advance the application of KV as a model to study insect immunity.

scholarly journals Mathematical Modeling of Autoimmune Diseases

Symmetry ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1457
Author(s):  
Mikhail Kolev
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Viral Infections ◽  
Nonequilibrium Statistical Mechanics ◽  
Good Health ◽  
The Body ◽  
Host Cells ◽  
Human Organism ◽  
Viral Particles ◽  
Harmful Effects

The human organism is a very complex system. To be in good health, its components must function properly. One of the most important systems of an organism is the immune system. It protects the body from the harmful effects of various external and internal agents. Sometimes, however, the immune system starts attacking its own healthy cells, tissues and organs. Then autoimmune diseases arise. They are widespread in recent decades. There is evidence that often autoimmune responses occur due to viral infections. In this paper, a new mathematical model of a general autoimmune disease is proposed. It describes the interactions between viral particles and host cells. The model is formulated by using integro-differential equations of Boltzmann type. This approach is typical for the nonequilibrium statistical mechanics. A preliminary qualitative and quantitative analysis of the model is presented.

scholarly journals Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Zhe Zou ◽  
Zhihua Meng ◽  
Chao Ma ◽  
Deguang Liang ◽  
Rui Sun ◽  
...  
Keyword(s):  
Immune System ◽  
Actin Filaments ◽  
Primary Infection ◽  
Rna Viruses ◽  
Critical Role ◽  
Host Cells ◽  
Host Immune System ◽  
Kshv Infection ◽  
Guanylate Binding Protein

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. In order to establish successful infection, KSHV has evolved numerous immune evasion strategies to bypass or hijack the host immune system. However, host cells still produce immune cytokines abundantly during primary KSHV infection. Whether the immune effectors produced are able to inhibit viral infection and how KSHV successfully conquers these immune effectors remain largely unknown. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on several RNA viruses; however, its function in DNA virus infection is less well understood. In this study, we found that KSHV infection increases both the transcriptional and protein levels of GBP1 at the early stage of primary infection by activating the NF-κB pathway. The overexpression of GBP1 significantly inhibited KSHV infection, while the knockdown of GBP1 promoted KSHV infection. The GTPase activity and dimerization of GBP1 were demonstrated to be responsible for its anti-KSHV activity. Furthermore, we found that GBP1 inhibited the nuclear delivery of KSHV virions by disrupting the formation of actin filaments. Finally, we demonstrated that replication and transcription activator (RTA) promotes the degradation of GBP1 through a proteasome pathway. Taken together, these results provide a new understanding of the antiviral mechanism of GBP1, which possesses potent anti-KSHV activity, and suggest the critical role of RTA in the evasion of the innate immune response during primary infection by KSHV. IMPORTANCE GBP1 can be induced by various cytokines and exerts antiviral activities against several RNA viruses. Our study demonstrated that GBP1 can exert anti-KSHV function by inhibiting the nuclear delivery of KSHV virions via the disruption of actin filaments. Moreover, we found that KSHV RTA can promote the degradation of GBP1 through a proteasome-mediated pathway. Taken together, our results elucidate a novel mechanism of GBP1 anti-KSHV activity and emphasize the critical role of RTA in KSHV evasion of the host immune system during primary infection.

scholarly journals Complexity and ultrastructure of infectious extracellular vesicles from cells infected by non-enveloped virus

2019 ◽  
Author(s):  
Jie E. Yang ◽  
Evan D. Rossignol ◽  
Deborah Chang ◽  
Joseph Zaia ◽  
Isaac Forrester ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Lysis ◽  
Viral Transmission ◽  
Viral Rna ◽  
Host Cells ◽  
Replication Proteins ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Positive Sense ◽  
Negative Sense

AbstractEnteroviruses support cell-to-cell viral transmission prior to their canonical lytic spread of virus. Poliovirus (PV), a prototype for human pathogenic positive-sense RNA enteroviruses, and picornaviruses in general, transport multiple virionsen blocvia infectious extracellular vesicles secreted from host cells. Using biochemical and biophysical methods we identify multiple components in these secreted vesicles, including PV virions; positive and negative-sense viral RNA; essential viral replication proteins; ribosomal and regulatory cellular RNAs; and numerous host cell proteins, such as regulators of cellular metabolism and structural remodeling. Using cryo-electron tomography, we visualize the near-native three-dimensional architecture of secreted infectious extracellular vesicles containing both virions and a unique mat-like structure. Based on our biochemical data (western blot, RNA-Seq, and mass spectrometry), these mat-like structures are expected to be comprised of unencapsidated RNA and proteins. Our data show that, prior to cell lysis, non-enveloped viruses are secreted within infectious vesicles that also transport viral and host RNAs and proteins.ImportanceThe family of picornaviridae is comprised of small positive-sense RNA viruses, many of which are significant human pathogens. Picornaviruses exploit secreted extracellular vesicles for cell-to-cell viral transmission without cell lysis, and poliovirus serves as a model system for picornaviruses that are not protected by a surrounding membrane (non-enveloped viruses). The structure and contents of these vesicles secreted by virus-infected cells are described here. In addition to mature virions, these vesicles carry negative-sense, ‘template’ viral RNA and essential replication proteins, as well as cellular resources from the host. Their complex contents may comprise an enhanced virulence factor for propagation of infection, and understanding their structure and function is helping elucidate the mechanism by which extracellular vesicles contribute to the spread of non-enveloped virus infection.

MicroRNAs in large herpesvirus DNA genomes: recent advances

2016 ◽  
Vol 7 (4) ◽  
pp. 229-239 ◽  
Author(s):  
Océane Sorel ◽  
Benjamin G. Dewals
Keyword(s):  
Mrna Translation ◽  
Large Family ◽  
Host Cells ◽  
Lymphoproliferative Diseases ◽  
Dna Viruses ◽  
Regulate Gene Expression ◽  
Double Stranded Dna ◽  
Recent Advances ◽  
Non Coding Rnas ◽  
Regulate Gene

AbstractMicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that regulate gene expression. They alter mRNA translation through base-pair complementarity, leading to regulation of genes during both physiological and pathological processes. Viruses have evolved mechanisms to take advantage of the host cells to multiply and/or persist over the lifetime of the host. Herpesviridae are a large family of double-stranded DNA viruses that are associated with a number of important diseases, including lymphoproliferative diseases. Herpesviruses establish lifelong latent infections through modulation of the interface between the virus and its host. A number of reports have identified miRNAs in a very large number of human and animal herpesviruses suggesting that these short non-coding transcripts could play essential roles in herpesvirus biology. This review will specifically focus on the recent advances on the functions of herpesvirus miRNAs in infection and pathogenesis.

Oncogenesis and the Lucké Virus

1968 ◽  
Vol 26 ◽  
pp. 200-201
Author(s):  
A. E. Vatter ◽  
J. Zambernard
Keyword(s):  
Rna Viruses ◽  
Vegetative State ◽  
Temperature Sensitive ◽  
Structural Level ◽  
Oncogenic Viruses ◽  
Dna Viruses ◽  
Leopard Frogs ◽  
Renal Adenocarcinoma ◽  
Induced Tumors ◽  
Northern Leopard Frogs

Oncogenic viruses, like viruses in general, can be divided into two classes, those that contain deoxyribonucleic acid (DNA) and those that contain ribonucleic acid (RNA). The RNA viruses have been recovered readily from the tumors which they cause whereas, the DNA-virus induced tumors have not yielded the virus. Since DNA viruses cannot be recovered, the bulk of present day investigations have been concerned with RNA viruses.The Lucké renal adenocarcinoma is a spontaneous tumor which occurs in northern leopard frogs (Rana pipiens) and has received increased attention in recent years because of its probable viral etiology. This hypothesis was first advanced by Lucké after he observed intranuclear inclusions in some of the tumor cells. Tumors with inclusions were examined at the fine structural level by Fawcett who showed that they contained immature and mature virus˗like particles.The use of this system in the study of oncogenic tumors offers several unique features, the virus has been shown to contain DNA and it can be recovered from the tumor, also, it is temperature sensitive. This latter feature is of importance because the virus can be transformed from a latent to a vegetative state by lowering or elevating the environmental temperature.

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