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Pediatrics International : Official... Sep 2021
Topics: COVID-19; Coinfection; Enterovirus Infections; Humans; Rhinovirus; SARS-CoV-2
PubMed: 33963633
DOI: 10.1111/ped.14582 -
Emerging Microbes & Infections Dec 2021Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never...
Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. ClinicalTrials.gov identifier: NCT02225769.
Topics: Child, Preschool; Fever; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Metagenomics; Retrospective Studies; Sequence Analysis, DNA; Sequence Analysis, RNA; Tanzania; Virus Diseases; Viruses
PubMed: 33929935
DOI: 10.1080/22221751.2021.1925161 -
Frontiers in Pediatrics 2021Human rhinoviruses (HRVs) are the leading cause of common colds. With the development of new molecular methods since the 2000s, HRVs have been increasingly involved... (Review)
Review
Human rhinoviruses (HRVs) are the leading cause of common colds. With the development of new molecular methods since the 2000s, HRVs have been increasingly involved among severe clinical infections. Recent knowledge of the HRV genetic characteristics has also improved the understanding of their pathogenesis. This narrative review aims to provide a current comprehensive knowledge about this virus in the pediatric community. HRVs represent a main cause of upper and lower respiratory tract infections in children. HRV is the second virus involved in bronchiolitis and pneumonia in children, and HRV bronchiolitis has a higher risk of recurrent wheezing episode or asthma. Some recent findings described HRVs in stools, blood, or cerebrospinal fluid, thanks to new molecular techniques such as polymerase chain reaction (PCR) by detecting HRVs with high sensibility. However, the high rate of asymptomatic carriage and the prolonged excretion in postsymptomatic patients complicate interpretation. No sufficient data exist to avoid antibiotic therapy in pediatric high-risk population with HRV detection. Severe clinical presentations due to HRVs can be more frequent in specific population with chronic pathology or genetic particularity. Inflammatory response is mediated by the nuclear factor (NF)-kappa B pathway and production of interferon (IFN)-beta and IFN-gamma, interleukin 8 (IL8), and IL1b. No specific treatment or antiviral therapy exists, although research is still ongoing. Nowadays, in addition to benign diseases, HRVs are recognized to be involved in some severe clinical presentations. Recent advances in genetic knowledge or specific inflammatory response may lead to specific treatment.
PubMed: 33829004
DOI: 10.3389/fped.2021.643219 -
Molecular Biology and Evolution May 2021Viral recombination is a major evolutionary mechanism driving adaptation processes, such as the ability of host-switching. Understanding global patterns of recombination...
Viral recombination is a major evolutionary mechanism driving adaptation processes, such as the ability of host-switching. Understanding global patterns of recombination could help to identify underlying mechanisms and to evaluate the potential risks of rapid adaptation. Conventional approaches (e.g., those based on linkage disequilibrium) are computationally demanding or even intractable when sequence alignments include hundreds of sequences, common in viral data sets. We present a comprehensive analysis of recombination across 30 genomic alignments from viruses infecting humans. In order to scale the analysis and avoid the computational limitations of conventional approaches, we apply newly developed topological data analysis methods able to infer recombination rates for large data sets. We show that viruses, such as ZEBOV and MARV, consistently displayed low levels of recombination, whereas high levels of recombination were observed in Sarbecoviruses, HBV, HEV, Rhinovirus A, and HIV. We observe that recombination is more common in positive single-stranded RNA viruses than in negatively single-stranded RNA ones. Interestingly, the comparison across multiple viruses suggests an inverse correlation between genome length and recombination rate. Positional analyses of recombination breakpoints along viral genomes, combined with our approach, detected at least 39 nonuniform patterns of recombination (i.e., cold or hotspots) in 18 viral groups. Among these, noteworthy hotspots are found in MERS-CoV and Sarbecoviruses (at spike, Nucleocapsid and ORF8). In summary, we have developed a fast pipeline to measure recombination that, combined with other approaches, has allowed us to find both common and lineage-specific patterns of recombination among viruses with potential relevance in viral adaptation.
Topics: Evolution, Molecular; Genetic Variation; Genome, Viral; Humans; Phylogeny; Recombination, Genetic; Viruses
PubMed: 33585889
DOI: 10.1093/molbev/msab046 -
Brazilian Journal of Microbiology :... Mar 2021Human rhinovirus (HRV) is one of the most common human viral pathogens related to infections of the upper and lower respiratory tract, which can result in bronchiolitis...
INTRODUCTION
Human rhinovirus (HRV) is one of the most common human viral pathogens related to infections of the upper and lower respiratory tract, which can result in bronchiolitis and pneumonia. However, the relevance of HRV in human health was under-estimated for long time due to the absence of molecular targets for influenza and influenza-like syndrome surveillance in Brasília, Brazil.
OBJECTIVES
The main objective of this study was analyze the clinical characteristics and outcomes of HRV infections in comparison with patients without HRV and other common respiratory viruses.
MATERIALS AND METHODS
For this purpose, new specific primer sets were designed based on the high throughput sequencing analysis in previous study. These primers were used for HRV detection by RT-qPCR and Sanger sequencing of amplified cDNA of 5' genomic region. The phylogenetic tree with representative HRV isolates was constructed using the Mega X software. Statistical analysis considering the patient profiles were performed using IBM SPSS program with non-parametric tests.
RESULTS
The most prevalent virus in negative samples was rhinovirus (n = 40), including three rhinovirus species (rhinovirus A, B, and C). The odds ratio associated with HRV infection was 2.160 for patients younger than 2 years and 4.367 for people living in rural areas. The multiple analysis showed lower chance of patients with HRV presenting respiratory distress.
CONCLUSION
In this study, it was reported the predominance of rhinoviruses in cases of respiratory illness for negative patients for the influenza and influenza-like syndrome surveillance, being rhinorrhea, the most significant symptom associated with the disease.
Topics: Brazil; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Phylogeny; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus; Viruses
PubMed: 33410102
DOI: 10.1007/s42770-020-00411-0 -
FASEB Journal : Official Publication of... Jan 2021Human Rhinovirus (HRV) is a major cause of common cold, bronchiolitis, and exacerbations of chronic pulmonary diseases such as asthma. CD8 T cell responses likely play...
Human Rhinovirus (HRV) is a major cause of common cold, bronchiolitis, and exacerbations of chronic pulmonary diseases such as asthma. CD8 T cell responses likely play an important role in the control of HRV infection but, surprisingly, HRV-specific CD8 T cell epitopes remain yet to be identified. Here, we approached the discovery and characterization of conserved HRV-specific CD8 T cell epitopes from species A (HRV A) and C (HRV C), the most frequent subtypes in the clinics of various pulmonary diseases. We found IFNγ-ELISPOT positive responses to 23 conserved HRV-specific peptides on peripheral blood mononuclear cells (PBMCs) from 14 HLA I typed subjects. Peptide-specific IFNγ production by CD8 T cells and binding to the relevant HLA I were confirmed for six HRV A-specific and three HRV C-specific CD8 T cell epitopes. In addition, we validated A*02:01-restricted epitopes by DimerX staining and found out that these peptides mediated cytotoxicity. All these A*02:01-restricted epitopes were 9-mers but, interestingly, we also identified and validated an unusually long 16-mer epitope peptide restricted by A*02:01, HRVC (GLEPLDLNTSAGFPYV). HRV-specific CD8 T cell epitopes describe here are expected to elicit CD8 T cell responses in up to 87% of the population and could be key for developing an HRV vaccine.
Topics: CD8-Positive T-Lymphocytes; Enterovirus; Epitopes, T-Lymphocyte; Female; HLA-A2 Antigen; Humans; Male; Peptides; Picornaviridae Infections; Viral Proteins
PubMed: 33230881
DOI: 10.1096/fj.202002165R -
Proceedings of the National Academy of... Nov 2020Human rhinoviruses (RVs) are positive-strand RNA viruses that cause respiratory tract disease in children and adults. Here we show that the innate immune signaling...
Human rhinoviruses (RVs) are positive-strand RNA viruses that cause respiratory tract disease in children and adults. Here we show that the innate immune signaling protein STING is required for efficient replication of members of two distinct RV species, RV-A and RV-C. The host factor activity of STING was identified in a genome-wide RNA interference (RNAi) screen and confirmed in primary human small airway epithelial cells. Replication of RV-A serotypes was strictly dependent on STING, whereas RV-B serotypes were notably less dependent. Subgenomic RV-A and RV-C RNA replicons failed to amplify in the absence of STING, revealing it to be required for a step in RNA replication. STING was expressed on phosphatidylinositol 4-phosphate (PI4P)-enriched membranes and was enriched in RV-A16 compared with RV-B14 replication organelles isolated in isopycnic gradients. The host factor activity of STING was species-specific, as murine STING (mSTING) did not rescue RV-A16 replication in STING-deficient cells. This species specificity mapped primarily to the cytoplasmic, ligand-binding domain of STING. Mouse-adaptive mutations in the RV-A16 2C protein allowed for robust replication in cells expressing mSTING, suggesting a role for 2C in recruiting STING to RV-A replication organelles. Palmitoylation of STING was not required for RV-A16 replication, nor was the C-terminal tail of STING that mediates IRF3 signaling. Despite co-opting STING to promote its replication, interferon signaling in response to STING agonists remained intact in RV-A16 infected cells. These data demonstrate a surprising requirement for a key host mediator of innate immunity to DNA viruses in the life cycle of a small pathogenic RNA virus.
Topics: Carrier Proteins; Common Cold; Enterovirus; HeLa Cells; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferon Regulatory Factor-3; Lipoylation; Membrane Proteins; Mutation; Protein Domains; Signal Transduction; Species Specificity; Viral Nonstructural Proteins; Virus Replication
PubMed: 33060297
DOI: 10.1073/pnas.2014940117 -
Indian Journal of Medical Microbiology 2019Human rhinovirus (HRV) and Enterovirus (ENV) are the major causes of childhood acute respiratory tract infections (ARTIs). This study sought to understand the...
INTRODUCTION
Human rhinovirus (HRV) and Enterovirus (ENV) are the major causes of childhood acute respiratory tract infections (ARTIs). This study sought to understand the distribution pattern of HRV subgroups, their seasonality and association with respiratory complications in patients at a tertiary care hospital.
RESULTS
Of the total 332 ARTI samples, 82 (24.7%) were positive for ENV/HRV. Twenty positive samples were processed further for phylogenetic analysis. Ten of the 20 samples were identified to be HRVs (70% HRV A and 30% HRV C) and nine were enteroviruses. HRV A clustered near three distinct HRV types (A12, A78 and A82). Four of the HRV strains (represented as SEQ 137 rhino, SEQ 282 rhino, SEQ 120 rhino and SEQ 82 rhino) had high sequence similarity. HRV C showed seasonality and was associated with disease severity.
CONCLUSION
The genotyping and phylogenetic analysis of the HRVs in the current study shows its circulatory pattern, association with risk factors and evolutionary dynamics.
Topics: Adolescent; Enterovirus; Enterovirus Infections; Female; Humans; India; Male; Nasopharynx; Phylogeny; Prospective Studies; RNA, Viral; Respiratory Tract Infections
PubMed: 32436882
DOI: 10.4103/ijmm.IJMM_20_23 -
Clinical Chemistry Jul 2020More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval,...
BACKGROUND
More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence.
METHODS
To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2.
RESULTS
Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms.
CONCLUSION
Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Enterovirus; Humans; Metagenomics; Nasopharynx; Pandemics; Phylogeny; Pneumonia, Viral; RNA, Viral; Real-Time Polymerase Chain Reaction; SARS-CoV-2; Sequence Analysis, RNA; Superinfection
PubMed: 32379863
DOI: 10.1093/clinchem/hvaa106 -
American Journal of Respiratory and... Jul 2020
Topics: Asthma; Child; Enterovirus; Humans; Lymphocytes; Picornaviridae Infections; Rhinovirus
PubMed: 32240597
DOI: 10.1164/rccm.202003-0634ED