RESUMO
Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying cas (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been exploited, leading to their development as highly effective tools for genome editing. The widespread use of CRISPR-Cas systems has driven a need for methods to control their activity. This review focuses on anti-CRISPRs (Acrs), proteins produced by viruses and other mobile genetic elements that can potently inhibit CRISPR-Cas systems. Discovered in 2013, there are now 54 distinct families of these proteins described, and the functional mechanisms of more than a dozen have been characterized in molecular detail. The investigation of Acrs is leading to a variety of practical applications and is providing exciting new insight into the biology of CRISPR-Cas systems.
Assuntos
Sistemas CRISPR-Cas/efeitos dos fármacos , Edição de Genes/métodos , Bibliotecas de Moléculas Pequenas/farmacologia , Proteínas Virais/genética , Vírus/genética , Archaea/genética , Archaea/imunologia , Archaea/virologia , Bactérias/genética , Bactérias/imunologia , Bactérias/virologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Coevolução Biológica , Proteínas Associadas a CRISPR/antagonistas & inibidores , Proteínas Associadas a CRISPR/genética , Proteínas Associadas a CRISPR/metabolismo , DNA/antagonistas & inibidores , DNA/química , DNA/genética , DNA/metabolismo , Clivagem do DNA/efeitos dos fármacos , Endodesoxirribonucleases/antagonistas & inibidores , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Humanos , Modelos Moleculares , Família Multigênica , Ligação Proteica , Multimerização Proteica/efeitos dos fármacos , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Virais/farmacologia , Vírus/metabolismo , Vírus/patogenicidadeRESUMO
Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.
Assuntos
Imunidade/genética , Viroses/imunologia , Apresentação de Antígeno/genética , Estudos de Coortes , Hematopoese/genética , Humanos , Interferons/sangue , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Mieloides/imunologia , Células Mieloides/patologia , Prognóstico , Índice de Gravidade de Doença , Biologia de Sistemas , Transcriptoma , Viroses/sangue , Viroses/classificação , Viroses/genética , Vírus/classificação , Vírus/patogenicidadeRESUMO
Many viral, protozoal, and fungal pathogens represent major human and animal health problems due to their great potential of causing infectious diseases. Research on these pathogens has contributed substantially to our current understanding of both microbial virulence determinants and host key factors during infection. Countless studies have also shed light on the molecular mechanisms of host-pathogen interactions that are employed by these microbes. For example, actin cytoskeletal dynamics play critical roles in effective adhesion, host cell entry, and intracellular movements of intruding pathogens. Cortactin is an eminent host cell protein that stimulates actin polymerization and signal transduction, and recently emerged as fundamental player during host-pathogen crosstalk. Here we review the important role of cortactin as major target for various prominent viral, protozoal and fungal pathogens in humans, and its role in human disease development and cancer progression. Most if not all of these important classes of pathogens have been reported to hijack cortactin during infection through mediating up- or downregulation of cortactin mRNA and protein expression as well as signaling. In particular, pathogen-induced changes in tyrosine and serine phosphorylation status of cortactin at its major phospho-sites (Y-421, Y-470, Y-486, S-113, S-298, S-405, and S-418) are addressed. As has been reported for various Gram-negative and Gram-positive bacteria, many pathogenic viruses, protozoa, and fungi also control these regulatory phospho-sites, for example, by activating kinases such as Src, PAK, ERK1/2, and PKD, which are known to phosphorylate cortactin. In addition, the recruitment of cortactin and its interaction partners, like the Arp2/3 complex and F-actin, to the contact sites between pathogens and host cells is highlighted, as this plays an important role in the infection process and internalization of several pathogens. However, there are also other ways in which the pathogens can exploit the function of cortactin for their needs, as the cortactin-mediated regulation of cellular processes is complex and involves numerous different interaction partners. Here, the current state of knowledge is summarized.
Assuntos
Cortactina , Fungos , Interações Hospedeiro-Patógeno , Cortactina/metabolismo , Humanos , Animais , Fungos/metabolismo , Fungos/patogenicidade , Vírus/metabolismo , Vírus/patogenicidade , Transdução de Sinais , Fosforilação , Viroses/metabolismoRESUMO
Cellular microRNAs serve key roles in the post-transcriptional regulation of almost every cellular gene-regulatory pathway, and it therefore is not surprising that viruses have found ways to subvert this process. Several viruses encode microRNAs that directly downregulate the expression of factors of the innate immune system, including proteins involved in promoting apoptosis and recruiting effector cells of the immune system. Viruses have also evolved the ability to downregulate or upregulate the expression of specific cellular miRNAs to enhance their replication. This Review provides an overview of the present knowledge of the complex interactions of viruses with the microRNA machinery of cells.
Assuntos
Evasão da Resposta Imune/genética , MicroRNAs/genética , Vírus , Animais , Apoptose , Citocinas/biossíntese , Citocinas/genética , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral , Vírus/genética , Vírus/imunologia , Vírus/patogenicidadeRESUMO
Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
Assuntos
Microbioma Gastrointestinal/genética , Doenças Inflamatórias Intestinais/microbiologia , Animais , Fungos/patogenicidade , Microbioma Gastrointestinal/imunologia , Saúde , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/virologia , Filogenia , Especificidade da Espécie , Transcriptoma , Vírus/patogenicidadeRESUMO
Infections can cause a multitude of stresses on the host and microbe. To detect potential infections, the mammalian immune system utilizes several families of pattern recognition receptors, which survey the intracellular and extracellular environments for microbial products. Members of each receptor family induce antimicrobial effector responses, which include inflammatory cytokine or interferon expression, downregulation of protein synthesis, or host cell death. In this review, we discuss the benefits of each of these innate immune responses. We highlight how non-infectious bacteria and viruses typically activate a single family of receptors, which results in a predictable host response. Infections with virulent pathogens, in contrast, may activate receptors from distinct families. As each receptor family may induce responses that antagonize or synergize with the activities of another family, cell fate decisions during pathogenic encounters are unpredictable. Understanding the antagonistic antimicrobial activities of the innate immune system should provide insight into how cell fate decisions are made during infections and potentially during other environmental stresses.
Assuntos
Bactérias/metabolismo , Infecções Bacterianas/metabolismo , Imunidade Inata , Receptores Imunológicos/metabolismo , Transdução de Sinais , Viroses/metabolismo , Vírus/metabolismo , Animais , Bactérias/imunologia , Bactérias/patogenicidade , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Ligantes , Fagócitos/imunologia , Fagócitos/metabolismo , Fagócitos/microbiologia , Fagócitos/virologia , Fagocitose , Piroptose , Receptores Imunológicos/imunologia , Virulência , Viroses/imunologia , Viroses/microbiologia , Vírus/imunologia , Vírus/patogenicidadeRESUMO
Microbes have been coevolving with their host for millions of years, exploiting host resources to their own benefit. We show that viral and bacterial pathogens convergently evolved to hijack cellular mitogen-activated protein kinase (MAPK) p90-ribosomal S6-kinases (RSKs). Theiler's virus leader (L) protein binds RSKs and prevents their dephosphorylation, thus maintaining the kinases active. Recruitment of RSKs enables L-protein-mediated inhibition of eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2 or PKR) and stress granule formation. Strikingly, ORF45 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) and YopM protein of Yersinia use the same peptide motif as L to recruit and activate RSKs. All three proteins interact with a conserved surface-located loop of RSKs, likely acting as an allosteric regulation site. Some unrelated viruses and bacteria thus evolved to harness RSKs in a common fashion, yet to target distinct aspects of innate immunity. As documented for Varicella zoster virus ORF11, additional pathogens likely evolved to hijack RSKs, using a similar short linear motif.
Assuntos
Interações entre Hospedeiro e Microrganismos/fisiologia , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Bactérias/patogenicidade , Infecções Bacterianas/genética , Infecções Bacterianas/metabolismo , Evolução Biológica , Linhagem Celular , Regulação Viral da Expressão Gênica/genética , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Proteínas Imediatamente Precoces/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Viroses/genética , Viroses/metabolismo , Replicação Viral/fisiologia , Vírus/patogenicidadeRESUMO
IMPORTANCE: The parasitic mite Varroa destructor is a significant driver of worldwide colony losses of our most important commercial pollinator, the Western honey bee Apis mellifera. Declines in honey bee health are frequently attributed to the viruses that mites vector to honey bees, yet whether mites passively transmit viruses as a mechanical vector or actively participate in viral amplification and facilitate replication of honey bee viruses is debated. Our work investigating the antiviral RNA interference response in V. destructor demonstrates that key viruses associated with honey bee declines actively replicate in mites, indicating that they are biological vectors, and the host range of bee-associated viruses extends to their parasites, which could impact virus evolution, pathogenicity, and spread.
Assuntos
Abelhas , Vetores de Doenças , Especificidade de Hospedeiro , Parasitos , Varroidae , Replicação Viral , Vírus , Animais , Abelhas/parasitologia , Abelhas/virologia , Parasitos/fisiologia , Parasitos/virologia , Varroidae/fisiologia , Varroidae/virologia , Vírus/crescimento & desenvolvimento , Vírus/patogenicidade , Interferência de RNARESUMO
BACKGROUND: More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC. OBJECTIVE: To analyze the characteristic microbes in AA. METHODS: Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and ß diversity. α diversity included box diagram, and ß diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed. RESULTS: The abundance of Prevotella sp900557255, Alistipes putredinis, and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus, Felixounavirus, and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D, Prevotella sp900557255, CAG-180 sp000432435, Phocaeicola plebeiuA, Teseptimavirus, Svunavirus, Felixounavirus, and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively. CONCLUSION: Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing.
Assuntos
Adenoma , Bactérias , Neoplasias Colorretais , Fezes , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Adenoma/microbiologia , Adenoma/virologia , Fezes/microbiologia , Fezes/virologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/virologia , Masculino , Pessoa de Meia-Idade , Feminino , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genética , Vírus/patogenicidade , Sequenciamento de Nucleotídeos em Larga Escala , Idoso , Aprendizado de MáquinaRESUMO
Identifying the animal reservoirs from which zoonotic viruses will likely emerge is central to understanding the determinants of disease emergence. Accordingly, there has been an increase in studies attempting zoonotic "risk assessment." Herein, we demonstrate that the virological data on which these analyses are conducted are incomplete, biased, and rapidly changing with ongoing virus discovery. Together, these shortcomings suggest that attempts to assess zoonotic risk using available virological data are likely to be inaccurate and largely only identify those host taxa that have been studied most extensively. We suggest that virus surveillance at the human-animal interface may be more productive.
Assuntos
Monitoramento Ambiental , Viroses , Zoonoses/etiologia , Zoonoses/prevenção & controle , Animais , Biodiversidade , Reservatórios de Doenças/classificação , Reservatórios de Doenças/estatística & dados numéricos , Monitoramento Ambiental/métodos , Monitoramento Ambiental/normas , Especificidade de Hospedeiro/genética , Humanos , Metagenômica/métodos , Metagenômica/organização & administração , Metagenômica/normas , Filogenia , Medição de Risco , Fatores de Risco , Viés de Seleção , Viroses/epidemiologia , Viroses/etiologia , Viroses/prevenção & controle , Viroses/transmissão , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação , Vírus/patogenicidade , Zoonoses/epidemiologia , Zoonoses/virologiaRESUMO
High-salt diets have recently been implicated in hypertension, cardiovascular disease, and autoimmune disease. However, whether and how dietary salt affects host antiviral response remain elusive. Here, we report that high salt induces an instant reduction in host antiviral immunity, although this effect is compromised during a long-term high-salt diet. Further studies reveal that high salt stimulates the acetylation at Lys663 of p97, which promotes the recruitment of ubiquitinated proteins for proteasome-dependent degradation. p97-mediated degradation of the deubiquitinase USP33 results in a deficiency of Viperin protein expression during viral infection, which substantially attenuates host antiviral ability. Importantly, switching to a low-salt diet during viral infection significantly enhances Viperin expression and improves host antiviral ability. These findings uncover dietary salt-induced regulation of ubiquitinated cellular proteins and host antiviral immunity, and could offer insight into the daily consumption of salt-containing diets during virus epidemics.
Assuntos
Fatores de Restrição Antivirais/imunologia , Imunidade Inata/efeitos dos fármacos , Cloreto de Sódio na Dieta/efeitos adversos , Viroses , Humanos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Ubiquitina Tiolesterase , Ubiquitinação , Viroses/imunologia , Vírus/patogenicidadeRESUMO
How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study.
Assuntos
Evolução Molecular , Genoma Viral , Filogenia , Vírus/genética , Vírus/patogenicidade , Animais , Humanos , VirulênciaRESUMO
Emerging infectious diseases significantly threaten global public health and socioeconomic security. The majority of emerging infectious disease outbreaks are caused by zoonotic/vector-borne viruses. Bats and rodents are the two most important reservoir hosts of many zoonotic viruses that can cross species barriers to infect humans, whereas mosquitos and ticks are well-established major vectors of many arboviral diseases. Moreover, some emerging zoonotic diseases require a vector to spread or are intrinsically vector-borne and zoonotically transmitted. In this study, we present a newly upgraded database of zoonotic and vector-borne viruses designated ZOVER (http://www.mgc.ac.cn/ZOVER). It incorporates two previously released databases, DBatVir and DRodVir, for bat- and rodent-associated viruses, respectively, and further collects up-to-date knowledge on mosquito- and tick-associated viruses to establish a comprehensive online resource for zoonotic and vector-borne viruses. Additionally, it integrates a set of online visualization tools for convenient comparative analyses to facilitate the discovery of potential patterns of virome diversity and ecological characteristics between/within different viral hosts/vectors. The ZOVER database will be a valuable resource for virologists, zoologists and epidemiologists to better understand the diversity and dynamics of zoonotic and vector-borne viruses and conduct effective surveillance to monitor potential interspecies spillover for efficient prevention and control of future emerging zoonotic diseases.
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Bases de Dados Factuais , Software , Viroses/epidemiologia , Vírus/patogenicidade , Zoonoses/epidemiologia , Animais , Quirópteros/virologia , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Culicidae/virologia , Conjuntos de Dados como Assunto , Vetores de Doenças/classificação , Monitoramento Epidemiológico , Interações Hospedeiro-Patógeno , Humanos , Internet , Anotação de Sequência Molecular , Roedores/virologia , Carrapatos/virologia , Viroses/transmissão , Viroses/virologia , Vírus/classificação , Vírus/genética , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.
Assuntos
Bases de Dados Factuais , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Receptores Virais/genética , Software , Viroses/genética , Vírus/genética , Animais , Sítios de Ligação , Conjuntos de Dados como Assunto , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , Anotação de Sequência Molecular , Ligação Proteica , Receptores Virais/classificação , Receptores Virais/metabolismo , Transdução de Sinais , Análise de Célula Única , Viroses/metabolismo , Viroses/transmissão , Viroses/virologia , Vírus/classificação , Vírus/metabolismo , Vírus/patogenicidadeRESUMO
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.
Assuntos
Bases de Dados Genéticas , Genoma Viral , Interações Hospedeiro-Patógeno/genética , RNA não Traduzido/genética , Software , Vírus/genética , Sítios de Ligação , Cromatina/química , Cromatina/metabolismo , Humanos , Internet , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Edição de RNA , RNA não Traduzido/classificação , RNA não Traduzido/metabolismo , Transdução de Sinais , Viroses/genética , Viroses/metabolismo , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/metabolismo , Vírus/patogenicidadeRESUMO
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.
Assuntos
Bases de Dados Factuais , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Software , Proteínas Virais/genética , Viroses/genética , Vírus/genética , Cromatina/química , Cromatina/metabolismo , Mineração de Dados , Regulação da Expressão Gênica , Histonas/genética , Histonas/metabolismo , Humanos , Internet , Mutação , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Virais/metabolismo , Viroses/metabolismo , Viroses/patologia , Viroses/virologia , Integração Viral/genética , Vírus/metabolismo , Vírus/patogenicidadeRESUMO
Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.
Assuntos
Disbiose , Viroses , Humanos , Disbiose/imunologia , Viroses/imunologia , Viroses/complicações , Viroses/virologia , Gastroenteropatias/virologia , Gastroenteropatias/imunologia , Gastroenteropatias/etiologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/virologia , Animais , Microbioma Gastrointestinal/imunologia , Vírus/imunologia , Vírus/patogenicidade , Doença Celíaca/virologia , Doença Celíaca/imunologia , ViromaRESUMO
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.
Assuntos
Degradação do RNAm Mediada por Códon sem Sentido , RNA Mensageiro/genética , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas Virais/genética , Viroses/genética , Vírus/genética , Códon sem Sentido , Interações Hospedeiro-Patógeno/genética , Humanos , Ligação Proteica , Biossíntese de Proteínas , RNA Helicases/genética , RNA Helicases/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Transdução de Sinais , Transativadores/genética , Transativadores/metabolismo , Proteínas Virais/metabolismo , Viroses/metabolismo , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/crescimento & desenvolvimento , Vírus/patogenicidadeRESUMO
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.
Assuntos
Endorribonucleases/genética , Estabilidade de RNA , RNA Mensageiro/genética , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas Virais/genética , Vírus/genética , Endorribonucleases/metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Transdução de Sinais , Especificidade por Substrato , Proteínas Virais/metabolismo , Viroses/genética , Viroses/metabolismo , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/crescimento & desenvolvimento , Vírus/patogenicidadeRESUMO
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.