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Open Forum Infectious Diseases Dec 2021Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their...
BACKGROUND
Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their long-term epidemiological patterns in a defined population remain limited.
METHODS
Here, we analyzed 1070 VP4/VP2 genomic region sequences sampled at Kilifi County Hospital on the Kenya coast. The samples were collected between 2007 and 2018 from hospitalized pediatric patients (<60 months of age) with acute respiratory illness.
RESULTS
Of 7231 children enrolled, RV was detected in 1497 (20.7%) and VP4/VP2 sequences were recovered from 1070 samples (71.5%). A total of 144 different RV types were identified (67 , 18 , and 59 ) and at any month, several types co-circulated with alternating predominance. Within types, multiple genetically divergent variants were observed. Ongoing RV infections through time appeared to be a combination of (1) persistent types (observed up to 7 consecutive months), (2) reintroduced genetically distinct variants, and (3) new invasions (average of 8 new types annually).
CONCLUSIONS
Sustained RV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than continuous transmission of locally established types/variants.
PubMed: 34988244
DOI: 10.1093/ofid/ofab571 -
Viruses Nov 2021Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we...
Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle.
Topics: 3C Viral Proteases; Antiviral Agents; Apoptosis; HeLa Cells; Host-Pathogen Interactions; Humans; Isoxazoles; Phenylalanine; Picornaviridae Infections; Protease Inhibitors; Pyrrolidinones; Rhinovirus; Valine
PubMed: 34960671
DOI: 10.3390/v13122402 -
Whole genome sequencing of two human rhinovirus A types (A101 and A15) detected in Kenya, 2016-2018.Wellcome Open Research 2021Virus genome sequencing is increasingly utilized in epidemiological surveillance. Genomic data allows comprehensive evaluation of underlying viral diversity and...
Virus genome sequencing is increasingly utilized in epidemiological surveillance. Genomic data allows comprehensive evaluation of underlying viral diversity and epidemiology to inform control. For human rhinovirus (HRV), genomic amplification and sequencing is challenging due to numerous types, high genetic diversity and inadequate reference sequences. We developed a tiled amplicon type-specific protocol for genome amplification and sequencing on the Illumina MiSeq platform of two HRV types, A15 and A101. We then assessed added value in analyzing whole genomes relative to the VP4/2 region only in the investigation of HRV molecular epidemiology within the community in Kilifi, coastal Kenya. We processed 73 nasopharyngeal swabs collected between 2016-2018, and 48 yielded at least 70% HRV genome coverage. These included all A101 samples (n=10) and 38 (60.3%) A15 samples. Phylogenetic analysis revealed that the Kilifi A101 sequences interspersed with global A101 genomes available in GenBank collected between 1999-2016. On the other hand, our A15 sequences formed a monophyletic group separate from the global genomes collected in 2008 and 2019. An improved phylogenetic resolution was observed with the genome phylogenies compared to the VP4/2 phylogenies. We present a type-specific full genome sequencing approach for obtaining HRV genomic data and characterizing infections.
PubMed: 34522789
DOI: 10.12688/wellcomeopenres.16911.2 -
Virology Journal Aug 2021Human rhinovirus (HRV) is one of the major viruses of acute respiratory tract disease among infants and young children. This work aimed to understand the epidemiological...
BACKGROUND
Human rhinovirus (HRV) is one of the major viruses of acute respiratory tract disease among infants and young children. This work aimed to understand the epidemiological and phylogenetic features of HRV in Guangzhou, China. In addition, the clinical characteristics of hospitalized children infected with different subtype of HRV was investigated.
METHODS
Hospitalized children aged < 14 years old with acute respiratory tract infections were enrolled from August 2018 to December 2019. HRV was screened for by a real-time reverse-transcription PCR targeting the viral 5'UTR.
RESULTS
HRV was detected in 6.41% of the 655 specimens. HRV infection was frequently observed in children under 2 years old (57.13%). HRV-A and HRV-C were detected in 18 (45%) and 22 (55%) specimens. All 40 HRV strains detected were classified into 29 genotypes. The molecular evolutionary rate of HRV-C was estimated to be 3.34 × 10 substitutions/site/year and was faster than HRV-A (7.79 × 10 substitutions/site/year). Children who experienced rhinorrhoea were more common in the HRV-C infection patients than HRV-A. The viral load was higher in HRV-C detection group than HRV-A detection group (p = 0.0148). The median peak symptom score was higher in patients with HRV-C infection as compared to HRV-A (p = 0.0543), even though the difference did not significance.
CONCLUSION
This study revealed the molecular epidemiological characteristics of HRV in patients with respiratory infections in southern China. Children infected with HRV-C caused more severe disease characteristics than HRV-A, which might be connected with higher viral load in patients infected with HRV-C. These findings will provide valuable information for the pathogenic mechanism and treatment of HRV infection.
Topics: Adolescent; Child; Child, Preschool; China; Enterovirus; Genetic Variation; Humans; Infant; Phylogeny; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus
PubMed: 34425845
DOI: 10.1186/s12985-021-01645-6 -
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