scholarly journals Recent Progress on Exosomes in RNA Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 256
Author(s):  
Liying Zhang ◽  
Yichen Ju ◽  
Si Chen ◽  
Linzhu Ren
Keyword(s):  
Rna Virus ◽  
Cell Types ◽  
Infection Process ◽  
Biologically Active ◽  
Pathological State ◽  
Virus Infections ◽  
Infected Cells ◽  
Host Genetic ◽  
Cell To Cell Transfer

Recent research indicates that most tissue and cell types can secrete and release membrane-enclosed small vesicles, known as exosomes, whose content reflects the physiological/pathological state of the cells from which they originate. These exosomes participate in the communication and cell-to-cell transfer of biologically active proteins, lipids, and nucleic acids. Studies of RNA viruses have demonstrated that exosomes release regulatory factors from infected cells and deliver other functional host genetic elements to neighboring cells, and these functions are involved in the infection process and modulate the cellular responses. This review provides an overview of the biogenesis, composition, and some of the most striking functions of exosome secretion and identifies physiological/pathological areas in need of further research. While initial indications suggest that exosome-mediated pathways operate in vivo, the exosome mechanisms involved in the related effects still need to be clarified. The current review focuses on the role of exosomes in RNA virus infections, with an emphasis on the potential contributions of exosomes to pathogenesis.

scholarly journals Exosome: A New Player in Translational Nanomedicine

2020 ◽  
Vol 9 (8) ◽  
pp. 2380 ◽  
Author(s):  
Houssam Aheget ◽  
María Tristán-Manzano ◽  
Loubna Mazini ◽  
Marina Cortijo-Gutierrez ◽  
Pablo Galindo-Moreno ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Types ◽  
Structural Features ◽  
Biologically Active ◽  
Biological Processes ◽  
New Approach ◽  
Current State ◽  
Exosome Biogenesis ◽  
Production Techniques

Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

scholarly journals Human cytomegalovirus modulation of CCR5 expression on myeloid cells affects susceptibility to human immunodeficiency virus type 1 infection

2006 ◽  
Vol 87 (8) ◽  
pp. 2171-2180 ◽  
Author(s):  
Christine A. King ◽  
Joan Baillie ◽  
John H. Sinclair
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Cytomegalovirus ◽  
Cell Types ◽  
Ccr5 Expression ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Bystander Cells ◽  
Hiv 1

For some time there has been evidence suggesting an interaction between human cytomegalovirus (HCMV) and Human immunodeficiency virus (HIV) in the pathogenesis of AIDS. Here, the interaction of HCMV and HIV-1 was examined in monocyte/macrophage cells, two cell types known to be targets for both viruses in vivo. Infection experiments demonstrated that prior infection with HCMV impeded subsequent superinfection with HIV-1. In contrast, uninfected bystander cells within the population were still permissive for HIV-1 infection and were also found to express increased levels of Gag after HIV-1 superinfection. Analysis of CCR5, a co-receptor for HIV-1, on HCMV-infected and bystander cells showed a substantial loss of surface CCR5 expression on infected cells due to HCMV-induced reduction of total cellular CCR5. In contrast, uninfected bystander cells displayed increased surface CCR5 expression. Furthermore, the data suggested that soluble factor(s) secreted from HCMV-infected cells were responsible for the observed upregulation of CCR5 on uninfected bystander cells. Taken together, these results suggest that, whilst HCMV-infected monocytes/macrophages are refractory to infection with HIV-1, HCMV-uninfected bystander cells within a population are more susceptible to HIV-1 infection. On this basis, HCMV infection may contribute to the pathogenesis of HIV-1.

Exploring HIV latency using transcription profiling

2017 ◽  
Vol 38 (3) ◽  
pp. 137
Author(s):  
Sushama Telwatte ◽  
Steven A Yukl
Keyword(s):  
Transcriptional Profiling ◽  
Cell Types ◽  
Hiv Latency ◽  
Dna Viruses ◽  
Major Barrier ◽  
Hiv Transcription ◽  
Latently Infected ◽  
Infected Cells ◽  
Mechanisms Of Persistence

The major barrier to a cure for HIV is the existence of reservoirs consisting predominantly of latently infected CD4+ T cells, which do not produce virus constitutively but can be induced to produce infectious virus on activation. HIV latency research has largely focused on peripheral blood, yet most HIV-infected cells reside in tissues, especially the gut, where differences in drug penetration, cell types, and immune responses may impact mechanisms of persistence. Exploring the differences between the gut and the blood in transcriptional blocks may reveal fundamental insights into mechanisms that contribute to HIV latency. Our novel transcriptional profiling assays enable us to determine where blocks to HIV transcription occur in various tissues and the magnitude of their contribution. These assays could also be adapted to investigate latency established by other retroviridae or even DNA viruses such as herpesviridae with a view to pinpointing mechanisms underlying latency in vivo and ultimately contribute to designing a cure.

scholarly journals Formation and Function of Liquid-Like Viral Factories in Negative-Sense Single-Stranded RNA Virus Infections

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 126
Author(s):  
Justin M. Su ◽  
Maxwell Z. Wilson ◽  
Charles E. Samuel ◽  
Dzwokai Ma
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Host Responses ◽  
Future Research ◽  
Virus Infections ◽  
Infected Cells ◽  
And Function ◽  
Negative Sense ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the cytoplasm of infected cells. These studies further reveal the structural and functional complexity of viral IB factories and provide a foundation for their future research. Herein, we review the literature leading to the discovery of LLPS-driven formation of IBs in NNS RNA virus-infected cells and the identification of viral scaffold components involved, and then outline important questions and challenges for IB assembly and disassembly. We discuss the functional implications of LLPS in the life cycle of NNS RNA viruses and host responses to infection. Finally, we speculate on the potential mechanisms underlying IB maturation, a phenomenon relevant to many human diseases.

scholarly journals Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders

2021 ◽  
Vol 16 (1) ◽  
pp. 431-441
Author(s):  
Arome Solomon Odiba ◽  
Nkwachukwu Oziamara Okoro ◽  
Olanrewaju Ayodeji Durojaye ◽  
Yanjun Wu
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Globin Gene ◽  
Severe Combined Immunodeficiency ◽  
Retinal Disease ◽  
Cell Types ◽  
Biologically Active ◽  
Hemophilia B ◽  
Combined Immunodeficiency

Abstract A new approach is adopted to treat primary immunodeficiency disorders, such as the severe combined immunodeficiency (SCID; e.g., adenosine deaminase SCID [ADA-SCID] and IL-2 receptor X-linked severe combined immunodeficiency [SCID-X1]). The success, along with the feasibility of gene therapy, is undeniable when considering the benefits recorded for patients with different classes of diseases or disorders needing treatment, including SCID-X1 and ADA-SCID, within the last two decades. β-Thalassemia and sickle cell anemia are two prominent monogenic blood hemoglobin disorders for which a solution has been sought using gene therapy. For instance, transduced autologous CD34+ HSCs via a self-inactivating (SIN)-Lentivirus (LV) coding for a functional copy of the β-globin gene has become a feasible procedure. adeno-associated virus (AAV) vectors have found application in ocular gene transfer in retinal disease gene therapy (e.g., Leber’s congenital amaurosis type 2), where no prior treatment existed. In neurodegenerative disorders, successes are now reported for cases involving metachromatic leukodystrophy causing severe cognitive and motor damage. Gene therapy for hemophilia also remains a viable option because of the amount of cell types that are capable of synthesizing biologically active FVIII and FIX following gene transfer using AAV vectors in vivo to correct hemophilia B (FIX deficiency), and it is considered an ideal target, as proven in preclinical studies. Recently, the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 gene-editing tool has taken a center stage in gene therapy research and is reported to be efficient and highly precise. The application of gene therapy to these areas has pushed forward the therapeutic clinical application.

scholarly journals Antiviral Role of Plant-Encoded RNA-Dependent RNA Polymerases Revisited with Deep Sequencing of Small Interfering RNAs of Virus Origin

2010 ◽  
Vol 23 (10) ◽  
pp. 1248-1252 ◽  
Author(s):  
Feng Qu
Keyword(s):  
Rna Virus ◽  
Rna Polymerases ◽  
Viral Rna ◽  
Antiviral Defense ◽  
Small Interfering Rnas ◽  
Virus Infections ◽  
Virus Origin ◽  
Infected Cells ◽  
Sequencing Platforms ◽  
Rna Accumulation

Several recent studies profiled virus-specific small interfering RNAs (vsRNAs) using next generation sequencing platforms and compellingly implicated plant-encoded RNA-dependent RNA polymerases (RDR) in vsRNA biogenesis and vsRNA-mediated antiviral defense. Specifically, both RDR1 and RDR6 were found to contribute to the accumulation of vsRNAs in virus-infected cells. While RDR1 was responsible for the majority of vsRNAs in plants infected with three different viruses, RDR6 acted as a surrogate when RDR1 function was disrupted. Mechanistically, vsRNAs associated with RDR1 mostly mapped to viral RNA regions close to the 5′ ends, whereas those associated with RDR6 mapped to more 3′ regions and appeared to be dependent on higher viral RNA concentrations. Knocking out both RDR1 and RDR6 led to drastically diminished vsRNA levels concomitant with enhanced viral RNA accumulation. In conclusion, these studies established that RDR1 and RDR6 function synergistically to contain RNA virus infections through the RNA silencing–based antiviral defense.

scholarly journals Identification and Characterization of Mefloquine Efficacy against JC Virus In Vitro

2009 ◽  
Vol 53 (5) ◽  
pp. 1840-1849 ◽  
Author(s):  
Margot Brickelmaier ◽  
Alexey Lugovskoy ◽  
Ramya Kartikeyan ◽  
Marta M. Reviriego-Mendoza ◽  
Norm Allaire ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cultured Cells ◽  
Jc Virus ◽  
Antiviral Treatment ◽  
Cell Types ◽  
Biologically Active ◽  
Biodistribution Data ◽  
Approved Drugs

ABSTRACT Progressive multifocal leukoencephalopathy (PML) is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals. Currently, no effective antiviral treatment for this disease has been identified. As a first step in the identification of such therapy, we screened the Spectrum collection of 2,000 approved drugs and biologically active molecules for their anti-JCV activities in an in vitro infection assay. We identified a number of different drugs and compounds that had significant anti-JCV activities at micromolar concentrations and lacked cellular toxicity. Of the compounds with anti-JCV activities, only mefloquine, an antimalarial agent, has been reported to show sufficiently high penetration into the central nervous system such that it would be predicted to achieve efficacious concentrations in the brain. Additional in vitro experiments demonstrated that mefloquine inhibits the viral infection rates of three different JCV isolates, JCV(Mad1), JCV(Mad4), and JCV(M1/SVEΔ), and does so in three different cell types, transformed human glial (SVG-A) cells, primary human fetal glial cells, and primary human astrocytes. Using quantitative PCR to quantify the number of viral copies in cultured cells, we have also shown that mefloquine inhibits viral DNA replication. Finally, we demonstrated that mefloquine does not block viral cell entry; rather, it inhibits viral replication in cells after viral entry. Although no suitable animal model of PML or JCV infection is available for the testing of mefloquine in vivo, our in vitro results, combined with biodistribution data published in the literature, suggest that mefloquine could be an effective therapy for PML.

scholarly journals Vaccinia Virus Infection during Murine Pregnancy: a New Pathogenesis Model for Vaccinia Fetalis

2004 ◽  
Vol 78 (6) ◽  
pp. 3133-3139 ◽  
Author(s):  
Nicola Benning ◽  
Daniel E. Hassett
Keyword(s):  
Vaccinia Virus ◽  
Virus Infections ◽  
Fatal Complication ◽  
Vertical Transfer ◽  
Maternal Infections ◽  
Acute Viral Infection ◽  
Infected Cells ◽  
Murine Pregnancy

ABSTRACT Vaccinia fetalis, the vertical transfer of vaccinia virus from mother to fetus, is a relatively rare but often fatal complication of primary vaccinia virus vaccination during pregnancy. To date there has been no attempt to develop an animal model to study the pathogenesis of this acute viral infection in vivo. Here we report that infection of gestating BALB/c mice by either intravenous or intraperitoneal routes with the Western Reserve strain of vaccinia virus results in the rapid colonization of the placenta and vertical transfer of virus to the developing fetus. Systemic maternal infections during gestation lead to the death of all offspring prior to or very shortly after birth. Using in situ hybridization for vaccinia virus mRNA to identify infected cells, we show that the virus initially colonizes cells lining maternal lacunae within the trophospongium layer of the placenta. The study of this model will significantly enhance our understanding of the pathogenesis of fetal vaccinia virus infections and aid in the development of effective treatments designed to reduce the risk of vaccinia virus-associated complications during pregnancy.

scholarly journals Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Brian Webster ◽  
Scott W Werneke ◽  
Biljana Zafirova ◽  
Sébastien This ◽  
Séverin Coléon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cell ◽  
Rna Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Virus Infections ◽  
Antiviral Responses ◽  
Infected Cells ◽  
Interferon Responses

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.

scholarly journals Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence

2017 ◽  
Author(s):  
Jie Xu ◽  
Yan Sun ◽  
Yize Li ◽  
Gordon Ruthel ◽  
Susan R. Weiss ◽  
...  
Keyword(s):  
Cell Fate ◽  
Sendai Virus ◽  
Rna Virus ◽  
Viral Persistence ◽  
Virus Infections ◽  
Viral Genomes ◽  
Persistent Infections ◽  
Infected Cells ◽  
Syncytial Virus ◽  
Survival Effect

ABSTRACTReplication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death and promote the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a MAVS-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses.

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