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Journal of Pathogens 2014We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses,... (Review)
Review
We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. Genus Enterovirus is classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B, and Rhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions.
PubMed: 25574400
DOI: 10.1155/2014/738512 -
PloS One 2014Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the...
Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species. Although emerging lineages within Rhinoviruses have been reported, their population structure has not been studied yet. The availability of complete genome sequences facilitates study of population structure, genetic diversity and underlying evolutionary forces, such as mutation, recombination and selection pressure. Analysis of complete genomes of Rhinoviruses using a model-based population genetics approach provided a strong evidence for existence of seven genetically distinct subpopulations. As a result of diversification, Rhinovirus A and -C populations are divided into four and two subpopulations, respectively. Genetically, the Rhinovirus B population was found to be homogeneous. Intra-species recombination was observed to be prominent in Rhinovirus A and -C species. Significant evidence of episodic positive selection was obtained for several sites within coding sequences of structural and non-structural proteins. This corroborates well with known phenotypic properties such as antigenicity of structural proteins. Episodic positive selection appears to be responsible for emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus population is an ensemble of seven distinct lineages. In case of Rhinovirus A, intra-species recombination and episodic positive selection contribute to its further diversification. In case of Rhinovirus C, intra- and inter-species recombinations are responsible for observed diversity. Population genetics approach was further useful to analyze phylogenetic tree topologies pertaining to recombinant strains, especially when trees are derived using complete genomes. Understanding of population structure serves as a foundation for designing new vaccines and drugs as well as to explain emergence of drug resistance amongst subpopulations.
Topics: Evolution, Molecular; Genetic Linkage; Genetic Variation; Genome, Viral; Humans; Phylogeny; RNA, Viral; Recombination, Genetic; Respiratory Tract Infections; Rhinovirus; Sequence Analysis, RNA
PubMed: 24586469
DOI: 10.1371/journal.pone.0088981 -
Pathogens (Basel, Switzerland) May 2024Enteroviruses are among the most common viruses pathogenic to humans. They are associated with various forms of disease, ranging from mild respiratory illness to severe...
Enteroviruses are among the most common viruses pathogenic to humans. They are associated with various forms of disease, ranging from mild respiratory illness to severe neurological diseases. In recent years, an increasing number of isolated cases of children developing meningitis or encephalitis as a result of enterovirus infection have been reported, as well as discrete enterovirus D68 outbreaks in North America in 2014 and 2016. We developed an assay to rapidly genotype enteroviruses by sequencing a region within the VP1 gene using nanopore Flongles. We retrospectively analyzed enterovirus-/rhinovirus-positive clinical samples from the Zurich, Switzerland area mainly collected during two seasons in 2019/2020 and 2021/2022. Respiratory, cerebrospinal fluid, and stool samples were analyzed. Whole-genome sequencing was performed on samples with ambiguous genotyping results and enterovirus D68-positive samples. Out of 255 isolates, a total of 95 different genotypes were found. A difference in the prevalence of enterovirus and rhinovirus infections was observed for both sample type and age group. In particular, children aged 0-4 years showed a higher frequency of enterovirus infections. Comparing the respiratory seasons, a higher prevalence was found, especially for enterovirus A and rhinovirus A after the SARS-CoV-2 pandemic. The enterovirus genotyping workflow provides a rapid diagnostic tool for individual analysis and continuous enterovirus surveillance.
PubMed: 38787241
DOI: 10.3390/pathogens13050390 -
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 -
Virology Journal Apr 2024In the aftermath of the COVID-19 pandemic, there has been a surge in human metapneumovirus (HMPV) transmission, surpassing pre-epidemic levels. We aim to elucidate the...
BACKGROUND
In the aftermath of the COVID-19 pandemic, there has been a surge in human metapneumovirus (HMPV) transmission, surpassing pre-epidemic levels. We aim to elucidate the clinical and epidemiological characteristics of HMPV infections in the post-COVID-19 pandemic era.
METHODS
In this retrospective single-center study, participants diagnosed with laboratory confirmed HMPV infection through Targeted Next Generation Sequencing were included. The study encompassed individuals admitted to Henan Children's Hospital between April 29 and June 5, 2023. Demographic information, clinical records, and laboratory indicators were analyzed.
RESULTS
Between April 29 and June 5, 2023, 96 pediatric patients were identified as infected with HMPV with a median age of 33.5 months (interquartile range, 12 ~ 48 months). The majority (87.5%) of infected children were under 5 years old. Notably, severe cases were statistically younger. Predominant symptoms included fever (81.3%) and cough (92.7%), with wheezing more prevalent in the severe group (56% vs 21.1%). Coinfection with other viruses was observed in 43 patients, with Epstein-Barr virus (EBV) (15.6%) or human rhinovirus A (HRV type A) (12.5%) being the most common. Human respiratory syncytial virus (HRSV) coinfection rate was significantly higher in the severe group (20% vs 1.4%). Bacterial coinfection occurred in 74 patients, with Haemophilus influenzae (Hin) and Streptococcus pneumoniae (SNP) being the most prevalent (52.1% and 41.7%, respectively). Severe patients demonstrated evidence of multi-organ damage. Noteworthy alterations included lower concentration of IL-12p70, decreased lymphocytes percentages, and elevated B lymphocyte percentages in severe cases, with statistical significance. Moreover, most laboratory indicators exhibited significant changes approximately 4 to 5 days after onset.
CONCLUSIONS
Our data systemically elucidated the clinical and epidemiological characteristics of pediatric patients with HMPV infection, which might be instructive to policy development for the prevention and control of HMPV infection and might provide important clues for future HMPV research endeavors.
Topics: Humans; China; Child, Preschool; Metapneumovirus; Retrospective Studies; Female; Male; Infant; Paramyxoviridae Infections; COVID-19; Child; Coinfection; SARS-CoV-2
PubMed: 38689312
DOI: 10.1186/s12985-024-02376-0 -
Virology Journal Nov 2012Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly...
BACKGROUND
Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly identified worldwide.
FINDINGS
In the present study, we report the frequency and diversity of Human Rhinovirus (HRV) strains circulating in Panama from children hospitalized with respiratory infections.
CONCLUSIONS
HRVs of species A, B and C have been identified with a predominance of HRV-A and HRV-C over HRV-B, and marked genetic diversity within each species.
Topics: Child, Hospitalized; Child, Preschool; Cluster Analysis; Female; Genetic Variation; Humans; Infant; Infant, Newborn; Male; Molecular Sequence Data; Panama; Phylogeny; Picornaviridae Infections; RNA, Viral; Respiratory Tract Infections; Rhinovirus; Sequence Analysis, DNA
PubMed: 23116216
DOI: 10.1186/1743-422X-9-257 -
Clinical Laboratory Aug 2023Although the detection of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was significantly reduced because of quarantine due...
BACKGROUND
Although the detection of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was significantly reduced because of quarantine due to the coronavirus disease (COVID-19) pandemic, an epidemic of several viruses was reported unexpectedly. We also detected a change in the pattern of human metapneumovirus (HMPV) outbreak compared to that before the COVID-19 pandemic. Therefore, the authors intended to identify the incidence and altered distribution pattern of the HMPV outbreak and provide useful information for clinical practice.
METHODS
This retrospective study investigated the incidence and distribution of HMPV from March 2020 to December 2022 during the COVID-19 pandemic. Detection of respiratory microorganisms was performed by multiplex polymerase chain reaction using a commercial kit and FilmArray assay.
RESULTS
The overall incidence of at least one respiratory microorganism was 50.3% (1,152/2,290). HMPV was not detected between March 2020 and June 2022. However, it was suddenly detected in July 2022 and continued for approximately five months until November 2022. In particular, the detection rate of HMPV was high in September and October 2022, accounting for approximately 76.1% (51/67) of the total HMPV-positive cases. Seasonally, 92.5% (62/67) of HMPV cases were detected in autumn, while the rest of the cases were detected in summer. The HMPV detection rate, according to the age group, was highest in group 4 (3 - 6 years) at 7.4% (27/367), followed by group 3 (4 months to 2 years) at 3.6% (31/861). In HMPV-positive cases, the rate of more than two respiratory pathogens was 46.3% (31/67). An analysis of co-infecting pathogens showed that HMPV with rhinovirus A/B/C/ enteroviruses accounted for the highest percentage (51.6%), followed by HMPV with respiratory syncytial virus (48.4%).
CONCLUSIONS
The COVID-19 pandemic has caused several changes in our lives. This study confirmed that the seasonal distribution of HMPV was different from that before the COVID-19 pandemic. Therefore, it can be assumed that the distribution of other respiratory microorganisms could have changed and it appears that changes could occur in previously known viral epidemiology. Clinicians should therefore be alert to this possibility.
Topics: Humans; Infant; Child, Preschool; Child; Metapneumovirus; Paramyxoviridae Infections; Pandemics; Retrospective Studies; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human; Viruses; Disease Outbreaks; Hospitals, University; Republic of Korea; Respiratory Tract Infections
PubMed: 37560859
DOI: 10.7754/Clin.Lab.2023.230216 -
American Journal of Respiratory Cell... Mar 2020Rhinovirus (RV) exposure evokes exacerbations of asthma that markedly impact morbidity and mortality worldwide. The mechanisms by which RV induces airway...
Rhinovirus (RV) exposure evokes exacerbations of asthma that markedly impact morbidity and mortality worldwide. The mechanisms by which RV induces airway hyperresponsiveness (AHR) or by which specific RV serotypes differentially evoke AHR remain unknown. We posit that RV infection evokes AHR and inflammatory mediator release, which correlate with degrees of RV infection. Furthermore, we posit that rhinovirus C-induced AHR requires paracrine or autocrine mediator release from epithelium that modulates agonist-induced calcium mobilization in human airway smooth muscle. In these studies, we used an model to measure bronchoconstriction and mediator release from infected airways in human precision cut lung slices to understand how RV exposure alters airway constriction. We found that rhinovirus C15 (RV-C15) infection augmented carbachol-induced airway narrowing and significantly increased release of IP-10 (IFN-γ-induced protein 10) and MIP-1β (macrophage inflammatory protein-1β) but not IL-6. RV-C15 infection of human airway epithelial cells augmented agonist-induced intracellular calcium flux and phosphorylation of myosin light chain in co-cultured human airway smooth muscle to carbachol, but not after histamine stimulation. Our data suggest that RV-C15-induced structural cell inflammatory responses are associated with viral load but that inflammatory responses and alterations in agonist-mediated constriction of human small airways are uncoupled from viral load of the tissue.
Topics: Asthma; Calcium Signaling; Carbachol; Cells, Cultured; Chemokine CXCL10; Enterovirus; Enterovirus Infections; Histamine; Humans; Inflammation Mediators; Muscle Contraction; Muscle, Smooth; Myocytes, Smooth Muscle; Myosin Light Chains; Phosphorylation; Protein Processing, Post-Translational; RNA, Viral; Respiratory Hypersensitivity; Viral Load
PubMed: 31533004
DOI: 10.1165/rcmb.2019-0004OC -
Cureus Sep 2022Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with...
Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with the severity of acute illness. This study aimed to determine whether purUUpurU content correlates with virulence in other single-strand RNA (ssRNA) viruses that vary in clinical severity. Methodology We determined the copy number of purUUpurU in the genomes of two subtypes of human respiratory syncytial virus (RSV), respiratory syncytial virus A (RSV-A), and respiratory syncytial virus B (RSV-B), which vary in clinical severity. In addition, we determined the purUUpurU content of the four ebolaviruses that cause human disease, dengue virus, rabies virus, human rhinovirus-A, poliovirus type 1, astrovirus, rubella, yellow fever virus, and measles virus. Viral nucleotide sequence files were downloaded from the National Center for Biotechnology Information (NCBI)/National Institutes of Health website. In addition, we determined the cumulative case fatality rate of 20 epidemics of the Ebola virus and compared it with that of the other human ebolaviruses. Results The genomic purUUpurU content correlated with the severity of acute illness caused by both subtypes of RSV and human ebolaviruses. The lowest purUUpurU content was in the genome of the rubella virus, which causes mild disease. Conclusions The quantity of genomic purUUpurU is a virulence factor in ssRNA viruses. Blood hyperviscosity is one mechanism by which purUUpurU causes pathology. Comparative quantitative genomic analysis for purUUpurU will be helpful in estimating the risk posed by emergent ssRNA viruses.
PubMed: 36284814
DOI: 10.7759/cureus.29340 -
Virology Journal Aug 2009Infection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in...
BACKGROUND
Infection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations. Given the absence of natural rhinovirus infections in rodents, we investigated whether an attenuated form of mengovirus, a picornavirus whose wild-type form causes systemic rather than respiratory infections in its natural rodent hosts, could induce airway infections in rats with inflammatory responses similar to those in human rhinovirus infections.
RESULTS
After inoculation with 10(7) plaque-forming units of attenuated mengovirus through an inhalation route, infectious mengovirus was consistently recovered on days 1 and 3 postinoculation from left lung homogenates (median Log10 plaque-forming units = 6.0 and 4.8, respectively) and right lung bronchoalveolar lavage fluid (median Log10 plaque-forming units = 5.8 and 4.0, respectively). Insufflation of attenuated mengovirus, but not vehicle or UV-inactivated virus, into the lungs of BN rats caused significant increases (P < 0.05) in lower airway neutrophils and lymphocytes in the bronchoalveolar lavage fluid and patchy peribronchiolar, perivascular, and alveolar cellular infiltrates in lung tissue sections. In addition, infection with attenuated mengovirus significantly increased (P < 0.05) lower airway levels of neutrophil chemoattractant CXCR2 ligands [cytokine-induced neutrophil chemoattractant-1 (CINC-1; CXCL1) and macrophage inflammatory protein-2 (MIP-2; CXCL2)] and monocyte chemoattractant protein-1 (MCP-1; CCL2) in comparison to inoculation with vehicle or UV-inactivated virus.
CONCLUSION
Attenuated mengovirus caused a respiratory infection in rats with several days of viral shedding accompanied by a lower airway inflammatory response consisting of neutrophils and lymphocytes. These features suggest that mengovirus-induced airway infection in rodents could be a useful model to define mechanisms of rhinovirus-induced airway inflammation in humans.
Topics: Animals; Disease Models, Animal; Humans; Inflammation; Lung; Lymphocytes; Male; Mengovirus; Neutrophils; Picornaviridae Infections; Rats; Respiratory Tract Infections; Virus Shedding
PubMed: 19671179
DOI: 10.1186/1743-422X-6-122