scholarly journals Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 656 ◽  
Author(s):  
Tasha M. Santiago-Rodriguez ◽  
Emily B. Hollister
Keyword(s):  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Endogenous Retroviruses ◽  
Present Review ◽  
Therapeutic Approaches ◽  
Human Gut ◽  
Bioinformatic Tools ◽  
Immunodeficiency Virus ◽  
Inflammatory Bowel

The virome is comprised of endogenous retroviruses, eukaryotic viruses, and bacteriophages and is increasingly being recognized as an essential part of the human microbiome. The human virome is associated with Type-1 diabetes (T1D), Type-2 diabetes (T2D), Inflammatory Bowel Disease (IBD), Human Immunodeficiency Virus (HIV) infection, and cancer. Increasing evidence also supports trans-kingdom interactions of viruses with bacteria, small eukaryotes and host in disease progression. The present review focuses on virus ecology and biology and how this translates mostly to human gut virome research. Current challenges in the field and how the development of bioinformatic tools and controls are aiding to overcome some of these challenges are also discussed. Finally, the present review also focuses on how human gut virome research could result in translational and clinical studies that may facilitate the development of therapeutic approaches.

scholarly journals The Dark Matter of Human Microbiota: Virobiota and Virome

2021 ◽  
Author(s):  
Gülendam Bozdayı ◽  
Işıl Fidan
Keyword(s):  
High Throughput Sequencing ◽  
Inflammatory Diseases ◽  
Human Microbiome ◽  
Endogenous Retroviruses ◽  
Therapeutic Approaches ◽  
Sequencing Technologies ◽  
Health And Disease ◽  
New Generation Sequencing ◽  
New Generation ◽  
Generation Sequencing

The viral component of the human microbiome is referred as ‘virobiota’. The virobiota is the sum of all viruses found in or on humans. The set of all genes of virobiota is referred as ‘virome’. The human virome consists of virus-derived genetic elements found in human genome constituted of viruses that infect eukaryotic cells, bacteriophages, prokaryotic cells, and, endogenous retroviruses. The development of new sequencing technologies, such as high-throughput sequencing techniques allowed the analysis of the human virome. Many new viruses have been discovered lately, using new generation sequencing technology. In recent years, there has been an increase in the studies of the human virome as changes in virome have been observed in diseases. The alterations in the human virome may be associated with infectious, inflammatory diseases, cancer and autoimmunity. The understanding of how the virome affects human health and disease can provide the development of potential therapeutic approaches that target the members of the virome.

scholarly journals GutCyc: a Multi-Study Collection of Human Gut Microbiome Metabolic Models

2016 ◽  
Author(s):  
Aria S. Hahn ◽  
Tomer Altman ◽  
Kishori M. Konwar ◽  
Niels W. Hanson ◽  
Dongjae Kim ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Therapeutic Interventions ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Disease States ◽  
Health And Disease ◽  
Inflammatory Bowel

AbstractAdvances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GUTCYC, a compendium of environmental pathway genome databases constructed from 418 assembled human microbiome datasets using METAPATHWAYS, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the PATHWAY TOOLS software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GUTCYC provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GUTCYC data products are searchable online, or may be downloaded and explored locally using METAPATHWAYS and PATHWAY TOOLS.

scholarly journals A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Maria I. Rojas ◽  
Giselle S. Cavalcanti ◽  
Katelyn McNair ◽  
Sean Benler ◽  
Amanda T. Alker ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gene Cluster ◽  
Bowel Disease ◽  
Human Microbiome ◽  
Gene Clusters ◽  
The United States ◽  
Injection System ◽  
Human Gut ◽  
Human Host ◽  
Inflammatory Bowel

ABSTRACT Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS—a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome. IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo. Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome.

scholarly journals Lack of Mutational Hot Spots during Decitabine-Mediated HIV-1 Mutagenesis

2015 ◽  
Vol 59 (11) ◽  
pp. 6834-6843 ◽  
Author(s):  
Jonathan M. O. Rawson ◽  
Sean R. Landman ◽  
Cavan S. Reilly ◽  
Laurent Bonnac ◽  
Steven E. Patterson ◽  
...  
Keyword(s):  
Hot Spots ◽  
Mutation Frequency ◽  
High Throughput Sequencing ◽  
Fold Increase ◽  
Lethal Mutagenesis ◽  
Immunodeficiency Virus ◽  
Mutagenic Effects ◽  
First Time ◽  
Hiv 1

ABSTRACTDecitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity.

scholarly journals Emerging Roles of Gut Virome in Pediatric Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4127
Author(s):  
Valerio Fulci ◽  
Laura Stronati ◽  
Salvatore Cucchiara ◽  
Ilaria Laudadio ◽  
Claudia Carissimi
Keyword(s):  
Metagenomic Data ◽  
Viral Population ◽  
Human Gut ◽  
Widespread Application ◽  
Shotgun Metagenomics ◽  
Pediatric Diseases ◽  
Inflammatory Bowel ◽  
Systematic Collection

In the last decade, the widespread application of shotgun metagenomics provided extensive characterization of the bacterial “dark matter” of the gut microbiome, propelling the development of dedicated, standardized bioinformatic pipelines and the systematic collection of metagenomic data into comprehensive databases. The advent of next-generation sequencing also unravels a previously underestimated viral population (virome) present in the human gut. Despite extensive efforts to characterize the human gut virome, to date, little is known about the childhood gut virome. However, alterations of the gut virome in children have been linked to pathological conditions such as inflammatory bowel disease, type 1 diabetes, malnutrition, diarrhea and celiac disease.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Entry in Cells Expressing gp41-Derived Peptides

2004 ◽  
Vol 78 (2) ◽  
pp. 568-575 ◽  
Author(s):  
Marc Egelhofer ◽  
Gunda Brandenburg ◽  
Holger Martinius ◽  
Patricia Schult-Dietrich ◽  
Gregory Melikyan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Heptad Repeat ◽  
Therapeutic Approaches ◽  
Transmembrane Glycoprotein ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1 ◽  
Maximal Expression

ABSTRACT As the limitations of antiretroviral drug therapy, such as toxicity and resistance, become evident, interest in alternative therapeutic approaches for human immunodeficiency virus (HIV) infection is growing. We developed the first gene therapeutic strategy targeting entry of a broad range of HIV type 1 (HIV-1) variants. Infection was inhibited at the level of membrane fusion by retroviral expression of a membrane-anchored peptide derived from the second heptad repeat of the HIV-1 gp41 transmembrane glycoprotein. To achieve maximal expression and antiviral activity, the peptide itself, the scaffold for presentation of the peptide on the cell surface, and the retroviral vector backbone were optimized. This optimized construct effectively inhibited virus replication in cell lines and primary blood lymphocytes. The membrane-anchored C-peptide was also shown to bind to free gp41 N peptides, suggesting that membrane-anchored antiviral C peptides have a mode of action similar to that of free gp41 C peptides. Preclinical toxicity and efficacy studies of this antiviral vector have been completed, and clinical trials are in preparation.

scholarly journals Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences

2008 ◽  
Vol 82 (17) ◽  
pp. 8743-8761 ◽  
Author(s):  
Andrew E. Armitage ◽  
Aris Katzourakis ◽  
Tulio de Oliveira ◽  
John J. Welch ◽  
Robert Belshaw ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human polynucleotide cytidine deaminases APOBEC3G (hA3G) and APOBEC3F (hA3F) are antiviral restriction factors capable of inducing extensive plus-strand guanine-to-adenine (G-to-A) hypermutation in a variety of retroviruses and retroelements, including human immunodeficiency virus type 1 (HIV-1). They differ in target specificity, favoring plus-strand 5′GG and 5′GA dinucleotide motifs, respectively. To characterize their mutational preferences in detail, we analyzed single-copy, near-full-length HIV-1 proviruses which had been hypermutated in vitro by hA3G or hA3F. hA3-induced G-to-A mutation rates were significantly influenced by the wider sequence context of the target G. Moreover, hA3G, and to a lesser extent hA3F, displayed clear tetranucleotide preference hierarchies, irrespective of the genomic region examined and overall hypermutation rate. We similarly analyzed patient-derived hypermutated HIV-1 genomes using a new method for estimating reference sequences. The majority of these, regardless of subtype, carried signatures of hypermutation that strongly correlated with those induced in vitro by hA3G. Analysis of genome-wide hA3-induced mutational profiles confirmed that hypermutation levels were reduced downstream of the polypurine tracts. Additionally, while hA3G mutations were found throughout the genome, hA3F often intensely mutated shorter regions, the locations of which varied between proviruses. We extended our analysis to human endogenous retroviruses (HERVs) from the HERV-K(HML2) family, finding two elements that carried clear footprints of hA3G activity. This constitutes the most direct evidence to date for hA3G activity in the context of natural HERV infections, demonstrating the involvement of this restriction factor in defense against retroviral attacks over millions of years of human evolution.

scholarly journals Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2944 ◽  
Author(s):  
Olga Tarasova ◽  
Sergey Ivanov ◽  
Dmitry A. Filimonov ◽  
Vladimir Poroikov
Keyword(s):  
Molecular Mechanisms ◽  
Antiretroviral Drugs ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Immunodeficiency Virus ◽  
Cycle Regulation ◽  
Text And Data Mining ◽  
Hiv 1

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.

scholarly journals Microbiome in Eosinophilic Esophagitis—Metagenomic, Metatranscriptomic, and Metabolomic Changes: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan D. Busing ◽  
Matthew Buendia ◽  
Yash Choksi ◽  
Girish Hiremath ◽  
Suman R. Das
Keyword(s):  
Systematic Review ◽  
Eosinophilic Esophagitis ◽  
High Throughput Sequencing ◽  
Human Microbiome ◽  
Gastrointestinal Diseases ◽  
Published Data ◽  
Human Gut ◽  
Esophageal Biopsy ◽  
Biochemical Alterations ◽  
Meta Analyses

Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE).Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed.Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included.Results: A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy (n = 3), esophageal string test (n = 1), salivary sampling (n = 1), or stool specimen (n = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy (n = 2) and blood plasma (n = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls.Conclusions: While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.

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