RESUMEN
Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity, or immunodeficiency. Programmed necrosis or necroptosis is a form of nonapoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate, mixed lineage kinase domain-like (MLKL). RIPK3 partners with its upstream adaptors RIPK1, TRIF, or DAI to signal for necroptosis in response to death receptor or Toll-like receptor stimulation, pathogen infection, or sterile cell injury. Necroptosis promotes inflammation through leakage of cellular contents from damaged plasma membranes. Intriguingly, many of the signal adaptors of necroptosis have dual functions in innate immune signaling. This unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury.
Asunto(s)
Inflamación/metabolismo , Inflamación/patología , Necrosis/metabolismo , Transducción de Señal , Animales , Infecciones Bacterianas/genética , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/patología , Evolución Biológica , Muerte Celular , Humanos , Inflamasomas/metabolismo , Inflamación/genética , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Enfermedades Parasitarias/genética , Enfermedades Parasitarias/metabolismo , Enfermedades Parasitarias/patología , Fosforilación , Unión Proteica , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ubiquitinación , Virosis/genética , Virosis/metabolismo , Virosis/patologíaRESUMEN
Natural killer (NK) cells are effector cells of the innate immune system and are important in the control of viral infections. Their relevance is reflected by the multiple mechanisms evolved by viruses to evade NK cell-mediated immune responses. Over recent years, our understanding of the interplay between NK cell immunity and viral pathogenesis has improved significantly. Here, we review the role of NK cells in the control of four important viral infections in humans: cytomegalovirus, influenza virus, HIV-1, and hepatitis C virus.
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Células Asesinas Naturales/inmunología , Células Asesinas Naturales/virología , Virosis/inmunología , Virosis/virología , Animales , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Infecciones por Citomegalovirus/prevención & control , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Infecciones por VIH/prevención & control , Hepatitis C/inmunología , Hepatitis C/patología , Hepatitis C/prevención & control , Hepatitis Viral Animal/inmunología , Hepatitis Viral Animal/patología , Hepatitis Viral Animal/prevención & control , Humanos , Gripe Humana/inmunología , Gripe Humana/patología , Gripe Humana/prevención & control , Células Asesinas Naturales/patología , Virosis/patologíaRESUMEN
Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We developed a viral exposure signature and validated the results in a longitudinal cohort with 173 at-risk patients who had long-term follow-up for HCC development. Our viral exposure signature significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87-0.96] at baseline and 0.98 [95% CI 0.97-1] at diagnosis). The signature identified cancer patients prior to a clinical diagnosis and was superior to alpha-fetoprotein. In summary, we established a viral exposure signature that can predict HCC among at-risk patients prior to a clinical diagnosis, which may be useful in HCC surveillance.
Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Virosis/patología , Adulto , Anciano , Área Bajo la Curva , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Bases de Datos Genéticas , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Curva ROC , Factores de Riesgo , Virosis/complicaciones , Adulto Joven , alfa-Fetoproteínas/análisisRESUMEN
Recent developments indicate that macrodomains, an ancient and diverse protein domain family, are key players in the recognition, interpretation, and turnover of ADP-ribose (ADPr) signaling. Crucial to this is the ability of macrodomains to recognize ADPr either directly, in the form of a metabolic derivative, or as a modification covalently bound to proteins. Thus, macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Their importance is further indicated by the fact that dysregulation or mutation of a macrodomain is associated with several diseases, including cancer, developmental defects, and neurodegeneration. In this review, we summarize the current insights into macrodomain evolution and how this evolution influenced their structural and functional diversification. We highlight some aspects of macrodomain roles in pathobiology as well as their emerging potential as therapeutic targets.
Asunto(s)
Reparación del ADN , Proteínas de Escherichia coli/química , Neoplasias/enzimología , Poli(ADP-Ribosa) Polimerasas/química , Procesamiento Proteico-Postraduccional , Proteínas Represoras/química , Virosis/enzimología , Adenosina Difosfato Ribosa/química , Adenosina Difosfato Ribosa/metabolismo , Animales , Daño del ADN , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Evolución Molecular , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Familia de Multigenes , Neoplasias/química , Neoplasias/genética , Neoplasias/patología , Filogenia , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Dominios Proteicos , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transducción de Señal , Homología Estructural de Proteína , Virosis/genética , Virosis/patología , Virosis/virologíaRESUMEN
The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.
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Enfermedades Transmisibles Emergentes/virología , Genitales Masculinos/virología , Virosis/virología , Humanos , Masculino , Virosis/patologíaRESUMEN
Much progress has been made in the identification of specific human gene variants that contribute to enhanced susceptibility or resistance to viral diseases. Herein we review multiple discoveries made with genome-wide or candidate gene approaches that have revealed significant insights into virus-host interactions. Genetic factors that have been identified include genes encoding virus receptors, receptor-modifying enzymes, and a wide variety of innate and adaptive immunity-related proteins. We discuss a range of pathogenic viruses, including influenza virus, respiratory syncytial virus, human immunodeficiency virus, human T cell leukemia virus, human papilloma virus, hepatitis B and C viruses, herpes simplex virus, norovirus, rotavirus, parvovirus, and Epstein-Barr virus. Understanding the genetic underpinnings that affect infectious disease outcomes should allow tailored treatment and prevention approaches in the future.
Asunto(s)
Inmunidad Adaptativa , Regulación de la Expresión Génica/inmunología , Predisposición Genética a la Enfermedad , Interacciones Huésped-Patógeno/genética , Inmunidad Innata , Virosis/genética , Citocinas/genética , Citocinas/inmunología , Estudio de Asociación del Genoma Completo , Interacciones Huésped-Patógeno/inmunología , Genética Humana , Humanos , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/inmunología , Receptores KIR/genética , Receptores KIR/inmunología , Receptores Virales/genética , Receptores Virales/inmunología , Transducción de Señal , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/genética , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/inmunología , Virosis/inmunología , Virosis/patología , Virosis/virologíaRESUMEN
Global attention is riveted on neurodegenerative diseases due to their unresolved aetiologies and lack of efficacious therapies. Two key factors implicated include mitochondrial impairment and microglial ageing. Several viral infections, including Herpes simplex virus-1 (HSV-1), human immunodeficiency virus (HIV) and Epstein-Barr virus, are linked to heightened risk of these disorders. Surprisingly, numerous studies indicate viruses induce these aforementioned precipitating events. Epstein-Barr virus, Hepatitis C Virus, HIV, respiratory syncytial virus, HSV-1, Japanese Encephalitis Virus, Zika virus and Enterovirus 71 specifically impact mitochondrial function, leading to mitochondrial malfunction. These vital organelles govern various cell activities and, under specific circumstances, trigger microglial ageing. This article explores the role of viral infections in elucidating the pathogenesis of neurodegenerative ailments. Various viruses instigate microglial ageing via mitochondrial destruction, causing senescent microglia to exhibit activated behaviour, thereby inducing neuroinflammation and contributing to neurodegeneration.
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Microglía , Mitocondrias , Enfermedades Neurodegenerativas , Virosis , Humanos , Enfermedades Neurodegenerativas/virología , Enfermedades Neurodegenerativas/patología , Mitocondrias/metabolismo , Virosis/virología , Virosis/patología , Microglía/virología , Microglía/patología , AnimalesRESUMEN
Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) serves as a prominent marker for lymphatic endothelial cells (LECs) and is pivotal in the process of lymphangiogenesis, a critical factor in cancer development and metastasis. Overexpression of LYVE-1 has been observed in various cancers, where it is recognized as an adverse prognostic indicator. Targeting LYVE-1 has demonstrated inhibitory effects on tumor cell proliferation, migration, and the formation of lymph node metastases both in vitro and in vivo. While extensive research has focused on the role of LYVE-1 in cancer cells, its involvement in virus infection and associated diseases remains largely unexplored. This review consolidates recent findings regarding the expression of LYVE-1 and its functions in lymphangiogenesis during various viral infections and the development of related diseases, with a particular emphasis on Kaposi's sarcoma herpesvirus. Despite the limited available data, it is evident that further studies are essential to comprehensively understand the contribution of LYVE-1 to viral pathogenesis and oncogenesis.
Asunto(s)
Neoplasias , Virosis , Humanos , Células Endoteliales/patología , Receptores de Hialuranos/metabolismo , Endotelio Linfático/metabolismo , Neoplasias/patología , Virosis/patologíaRESUMEN
As a means to aid in the investigation of viral infection mechanisms and identification of more effective antivirus targets, the availability of a source which continually collects and updates information on the virus and host ncRNA-associated interaction resources is essential. Here, we update the ViRBase database to version 3.0 (http://www.virbase.org/ or http://www.rna-society.org/virbase/). This update represents a major revision: (i) the total number of interaction entries is now greater than 820,000, an approximately 70-fold increment, involving 116 virus and 36 host organisms, (ii) it supplements and provides more details on RNA annotations (including RNA editing, RNA localization and RNA modification), ncRNA SNP and ncRNA-drug related information and (iii) it provides two additional tools for predicting binding sites (IntaRNA and PRIdictor), a visual plug-in to display interactions and a website which is optimized for more practical and user-friendly operation. Overall, ViRBase v3.0 provides a more comprehensive resource for virus and host ncRNA-associated interactions enabling researchers a more effective means for investigation of viral infections.
Asunto(s)
Bases de Datos Genéticas , Genoma Viral , Interacciones Huésped-Patógeno/genética , ARN no Traducido/genética , Programas Informáticos , Virus/genética , Sitios de Unión , Cromatina/química , Cromatina/metabolismo , Humanos , Internet , Anotación de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Edición de ARN , ARN no Traducido/clasificación , ARN no Traducido/metabolismo , Transducción de Señal , Virosis/genética , Virosis/metabolismo , Virosis/patología , Virosis/virología , Virus/clasificación , Virus/metabolismo , Virus/patogenicidadRESUMEN
Molecular mechanisms of virus-related diseases involve multiple factors, including viral mutation accumulation and integration of a viral genome into the host DNA. With increasing attention being paid to virus-mediated pathogenesis and the development of many useful technologies to identify virus mutations (VMs) and viral integration sites (VISs), much research on these topics is available in PubMed. However, knowledge of VMs and VISs is widely scattered in numerous published papers which lack standardization, integration and curation. To address these challenges, we built a pilot database of human disease-related Virus Mutations, Integration sites and Cis-effects (ViMIC), which specializes in three features: virus mutation sites, viral integration sites and target genes. In total, the ViMIC provides information on 31 712 VMs entries, 105 624 VISs, 16 310 viral target genes and 1 110 015 virus sequences of eight viruses in 77 human diseases obtained from the public domain. Furthermore, in ViMIC users are allowed to explore the cis-effects of virus-host interactions by surveying 78 histone modifications, binding of 1358 transcription regulators and chromatin accessibility on these VISs. We believe ViMIC will become a valuable resource for the virus research community. The database is available at http://bmtongji.cn/ViMIC/index.php.
Asunto(s)
Bases de Datos Factuales , Genoma Viral , Interacciones Huésped-Patógeno/genética , Programas Informáticos , Proteínas Virales/genética , Virosis/genética , Virus/genética , Cromatina/química , Cromatina/metabolismo , Minería de Datos , Regulación de la Expresión Génica , Histonas/genética , Histonas/metabolismo , Humanos , Internet , Mutación , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Virales/metabolismo , Virosis/metabolismo , Virosis/patología , Virosis/virología , Integración Viral/genética , Virus/metabolismo , Virus/patogenicidadRESUMEN
Virus infection causes major rearrangements in the subcellular architecture of eukaryotes, but its impact in prokaryotic cells was much less characterized. Here, we show that infection of the bacterium Bacillus subtilis by bacteriophage SPP1 leads to a hijacking of host replication proteins to assemble hybrid viral-bacterial replisomes for SPP1 genome replication. Their biosynthetic activity doubles the cell total DNA content within 15 min. Replisomes operate at several independent locations within a single viral DNA focus positioned asymmetrically in the cell. This large nucleoprotein complex is a self-contained compartment whose boundaries are delimited neither by a membrane nor by a protein cage. Later during infection, SPP1 procapsids localize at the periphery of the viral DNA compartment for genome packaging. The resulting DNA-filled capsids do not remain associated to the DNA transactions compartment. They bind to phage tails to build infectious particles that are stored in warehouse compartments spatially independent from the viral DNA. Free SPP1 structural proteins are recruited to the dynamic phage-induced compartments following an order that recapitulates the viral particle assembly pathway. These findings show that bacteriophages restructure the crowded host cytoplasm to confine at different cellular locations the sequential processes that are essential for their multiplication.
Asunto(s)
Bacillus subtilis/virología , Compartimento Celular , Virosis/patología , Bacillus subtilis/ultraestructura , Bacteriófagos/fisiología , Bacteriófagos/ultraestructura , Cápside/metabolismo , Replicación del ADN , ADN Viral/biosíntesis , ADN Polimerasa Dirigida por ADN , Interacciones Huésped-Patógeno , Complejos Multienzimáticos , Factores de Tiempo , Virión/metabolismoRESUMEN
Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.
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Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Infecciones del Sistema Respiratorio , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo , Humanos , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/metabolismo , Infecciones del Sistema Respiratorio/patología , Animales , Virosis/metabolismo , Virosis/complicaciones , Virosis/patología , Virosis/virologíaRESUMEN
The Nonsense-mediated mRNA Decay (NMD) pathway is an RNA quality control pathway conserved among eukaryotic cells. While historically thought to predominantly recognize transcripts with premature termination codons, it is now known that the NMD pathway plays a variety of roles, from homeostatic events to control of viral pathogens. In this review we highlight the reciprocal interactions between the host NMD pathway and viral pathogens, which have shaped both the host antiviral defense and viral pathogenesis.
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Degradación de ARNm Mediada por Codón sin Sentido , ARN Mensajero/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas Virales/genética , Virosis/genética , Virus/genética , Codón sin Sentido , Interacciones Huésped-Patógeno/genética , Humanos , Unión Proteica , Biosíntesis de Proteínas , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Transducción de Señal , Transactivadores/genética , Transactivadores/metabolismo , Proteínas Virales/metabolismo , Virosis/metabolismo , Virosis/patología , Virosis/virología , Virus/clasificación , Virus/crecimiento & desarrollo , Virus/patogenicidadRESUMEN
As obligate intracellular parasites with limited coding capacity, RNA viruses rely on host cells to complete their multiplication cycle. Viral RNAs (vRNAs) are central to infection. They carry all the necessary information for a virus to synthesize its proteins, replicate and spread and could also play essential non-coding roles. Regardless of its origin or tropism, vRNA has by definition evolved in the presence of host RNA Binding Proteins (RBPs), which resulted in intricate and complicated interactions with these factors. While on one hand some host RBPs recognize vRNA as non-self and mobilize host antiviral defenses, vRNA must also co-opt other host RBPs to promote viral infection. Focusing on pathogenic RNA viruses, we will review important scenarios of RBP-vRNA interactions during which host RBPs recognize, modify or degrade vRNAs. We will then focus on how vRNA hijacks the largest ribonucleoprotein complex (RNP) in the cell, the ribosome, to selectively promote the synthesis of its proteins. We will finally reflect on how novel technologies are helping in deepening our understanding of vRNA-host RBPs interactions, which can be ultimately leveraged to combat everlasting viral threats.
Asunto(s)
Virus ARN/genética , ARN Mensajero/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas Virales/genética , Virosis/genética , Factores Eucarióticos de Iniciación/genética , Factores Eucarióticos de Iniciación/inmunología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata/genética , Unión Proteica , Biosíntesis de Proteínas , Virus ARN/crecimiento & desarrollo , Virus ARN/patogenicidad , ARN Mensajero/inmunología , ARN Viral/inmunología , Proteínas de Unión al ARN/inmunología , Ribosomas/genética , Ribosomas/metabolismo , Transducción de Señal , Proteínas Virales/metabolismo , Ensamble de Virus/genética , Virosis/inmunología , Virosis/patología , Virosis/virologíaRESUMEN
For over a decade, studies of messenger RNA regulation have revealed an unprecedented level of connectivity between the RNA pool and global gene expression. These connections are underpinned by a vast array of RNA elements that coordinate RNA-protein and RNA-RNA interactions, each directing mRNA fate from transcription to translation. Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as "Host Shutoff". This takeover of the host cell is mechanistically orchestrated by a number of non-homologous virally encoded endoribonucleases. Recent large-scale screens estimate that over 70 % of the host transcriptome is decimated by the expression of these viral nucleases. While this takeover strategy seems extraordinarily well conserved, each viral endonuclease has evolved to target distinct mRNA elements. Herein, we will explore each of these RNA structures/sequence features that render messenger RNA susceptible or resistant to viral endonuclease cleavage. By further understanding these targeting and escape mechanisms we will continue to unravel untold depths of cellular RNA regulation that further underscores the integral relationship between RNA fate and the fate of the cell.
Asunto(s)
Endorribonucleasas/genética , Estabilidad del ARN , ARN Mensajero/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas Virales/genética , Virus/genética , Endorribonucleasas/metabolismo , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Transducción de Señal , Especificidad por Sustrato , Proteínas Virales/metabolismo , Virosis/genética , Virosis/metabolismo , Virosis/patología , Virosis/virología , Virus/clasificación , Virus/crecimiento & desarrollo , Virus/patogenicidadRESUMEN
Neurological disorders are challenging to study given the complexity and species-specific features of the organ system. Brain organoids are three dimensional structured aggregates of neural tissue that are generated by self-organization and differentiation from pluripotent stem cells under optimized culture conditions. These brain organoids exhibit similar features of structural organization and cell type diversity as the developing human brain, creating opportunities to recapitulate disease phenotypes that are not otherwise accessible. Here we review the initial attempt in the field to apply brain organoid models for the study of many different types of human neurological disorders across a wide range of etiologies and pathophysiologies. Forthcoming advancements in both brain organoid technology as well as analytical methods have significant potentials to advance the understanding of neurological disorders and to uncover opportunities for meaningful therapeutic intervention.
Asunto(s)
Encéfalo/metabolismo , Modelos Biológicos , Proteínas del Tejido Nervioso/genética , Enfermedades del Sistema Nervioso/genética , Enfermedades Neurodegenerativas/genética , Neuronas/metabolismo , Organoides/metabolismo , Encéfalo/patología , Diferenciación Celular , Células Ependimogliales/citología , Células Ependimogliales/metabolismo , Regulación de la Expresión Génica , Humanos , Mutación , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/virología , Proteínas del Tejido Nervioso/metabolismo , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/patología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/virología , Neuronas/citología , Organoides/patología , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Cultivo Primario de Células , Virosis/genética , Virosis/metabolismo , Virosis/patología , Virosis/virologíaRESUMEN
Tight regulation of the immune response is fundamental for efficient pathogen clearance and to prevent excessive inflammation. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of the innate and adaptive immune responses to viral pathogens. Host-derived lncRNAs control the differentiation and polarization of immune cell populations and the production of cytokines, interferons and antiviral factors. This review provides an updated overview of lncRNAs that modulate viral replication or pathogenesis. Beyond that, viruses have developed lncRNA-based strategies to mask themselves from immune detection and evade antiviral immunity. A deeper understanding of lncRNA biology in the context of host-pathogen interactions may unveil new treatment strategies in the near future.
Asunto(s)
Inmunidad Innata/genética , ARN Largo no Codificante/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Virosis/genética , Virus/genética , Regulación de la Expresión Génica , Humanos , Evasión Inmune/genética , Interferones/genética , Interferones/inmunología , Interleucinas/genética , Interleucinas/inmunología , MicroARNs/genética , MicroARNs/inmunología , Moléculas de Patrón Molecular Asociado a Patógenos/inmunología , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , ARN Largo no Codificante/inmunología , ARN Mensajero/genética , ARN Mensajero/inmunología , ARN Viral/inmunología , Proteínas de Unión al ARN/inmunología , Transducción de Señal , Virosis/inmunología , Virosis/patología , Virosis/virología , Replicación Viral , Virus/crecimiento & desarrollo , Virus/patogenicidadRESUMEN
RNA is a central molecule in RNA virus biology due to its dual function as messenger and genome. However, the small number of proteins encoded by viral genomes is insufficient to enable virus infection. Hence, viruses hijack cellular RNA-binding proteins (RBPs) to aid replication and spread. In this review we discuss the 'knowns' and 'unknowns' regarding the contribution of host RBPs to the formation of viral particles and the initial steps of infection in the newly infected cell. Through comparison of the virion proteomes of ten different human RNA viruses, we confirm that a pool of cellular RBPs are typically incorporated into viral particles. We describe here illustrative examples supporting the important functions of these RBPs in viral particle formation and infectivity and we propose that the role of host RBPs in these steps can be broader than previously anticipated. Understanding how cellular RBPs regulate virus infection can lead to the discovery of novel therapeutic targets against viruses.
Asunto(s)
ARN Mensajero/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas Virales/genética , Virión/genética , Virosis/genética , Virus/genética , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Unión Proteica , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Transducción de Señal , Proteínas Virales/metabolismo , Virión/crecimiento & desarrollo , Virión/metabolismo , Ensamble de Virus , Virosis/metabolismo , Virosis/patología , Virosis/virología , Replicación Viral , Virus/clasificación , Virus/crecimiento & desarrollo , Virus/patogenicidadRESUMEN
Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections.
Asunto(s)
Antivirales/farmacología , Coinfección/prevención & control , Inmunidad/inmunología , Schistosoma/inmunología , Esquistosomiasis/complicaciones , Virosis/prevención & control , Virus/inmunología , Animales , Coinfección/etiología , Coinfección/patología , Humanos , Esquistosomiasis/parasitología , Virosis/etiología , Virosis/patologíaRESUMEN
Reactive oxygen species (ROS) are by-products of cellular metabolism and can be either beneficial, at low levels, or deleterious, at high levels, to the cell. It is known that several viral infections can increase oxidative stress, which is mainly facilitated by viral-induced imbalances in the antioxidant defence mechanisms of the cell. While the exact role of ROS in certain viral infections (adenovirus and dengue virus) remains unknown, other viruses can use ROS for enhancement of pathogenesis (SARS coronavirus and rabies virus) or replication (rhinovirus, West Nile virus and vesicular stomatitis virus) or both (hepatitis C virus, human immunodeficiency virus and influenza virus). While several viral proteins (mainly for hepatitis C and human immunodeficiency virus) have been identified to play a role in ROS formation, most mediators of viral ROS modulation are yet to be elucidated. Treatment of viral infections, including hepatitis C virus, human immunodeficiency virus and influenza virus, with ROS inhibitors has shown a decrease in both pathogenesis and viral replication both in vitro and in animal models. Clinical studies indicating the potential for targeting ROS-producing pathways as possible broad-spectrum antiviral targets should be evaluated in randomized controlled trials.