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Discovery of a subgenotype of human coronavirus NL63 associated with severe lower respiratory tract infection in China, 2018.

ABSTRACT: Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7034077 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Human coronavirus NL63 infections in infants hospitalised with acute respiratory tract infections in South Africa.

Project description:BackgroundHuman coronavirus NL63 (HCoV-NL63) is a novel respiratory virus which is associated with respiratory tract infections in children.ObjectiveTo determine the role of HCoV-NL63 in infants and young children hospitalised with acute respiratory tract infections (ARI) in Cape Town, South Africa.MethodsRespiratory specimens were collected from 1055 infants and young children hospitalised with ARI in 2003-2004. Samples were screened by RT-PCR to detect HCoV-NL63 and human metapneumovirus (hMPV). Standard shell vial culture and immunofluoresence was used to detect the common respiratory viruses including RSV, influenza A and B viruses, parainfluenza viruses 1, 2, 3, adenovirus and CMV.ResultsA respiratory virus was found in 401/1055 (38.0%) samples. HCoV-NL63 was detected in 9/1055 (0.85%) with peak activity during autumn (67%). Most patients had a diagnosis of pneumonia or lower respiratory tract infection (6/9; 67%).ConclusionsThis is the first report of HCoV-NL63 infections in hospitalised children in Africa. During the 2-year period HCoV-NL63 played a minor role in ARI in children.

| S-EPMC4634228 | biostudies-literature

Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2.

Project description:Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.

| S-EPMC2886958 | biostudies-literature

Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continue to impact countries worldwide. At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-CoV-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-CoV-2-infected monkeys. We also detected anti-SARS-CoV-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-CoV-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG) antibodies were not detected in 6.90% of COVID-19 patients. Furthermore, integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-CoV-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus, SARS-CoV-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-CoV-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.

| S-EPMC7995275 | biostudies-literature

The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2.

Project description:The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group II coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by beta-strands 4 and 5.

| S-EPMC2693060 | biostudies-literature

LPS-induced IFN networks predict severe viral Lower Respiratory tract Infections in infancy

Project description:Severe LRIs are a major cause of infant/child hospitalization and a risk factors for asthma pathogenisis. Innate immune interactions with microbial pathogens, esp. in early life, underpin risk. We aimed to characterize cord blood mononuclear cell (CBMC) responses to activation of micriobial recognition receptors (TLRs 3, 4, & 7) and identify response pattern variations associated withsLRI susceptibility in infancy.

2022-08-24 | GSE184383 | GEO

Human lower respiratory tract

Project description:Analyses of human lung metagenome by nanopore sequencing

| PRJNA720304 | ENA

Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China.

Project description:BackgroundHuman coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43).MethodsWe investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002.ResultsCoronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (+/- standard deviation [SD]) of the infected children was 30.7 +/- 19.8 months (range, 6-57 months). The mean maximum temperature (+/- SD) for the 12 children who were febrile was 39.3 degrees C +/- 0.9 degrees C, and the mean total duration of fever (+/- SD) for all children was 2.6 +/- 1.2 days (range, 1-5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season.ConclusionsHCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged < or = 6 years each year in Hong Kong.

| S-EPMC7107956 | biostudies-literature

Detection of human coronavirus NL63, human metapneumovirus and respiratory syncytial virus in children with respiratory tract infections in south-west Sweden.

Project description:Two recently detected viruses, human metapneumovirus (hMPV) and coronavirus NL63 (HCoV-NL63), have been associated with acute respiratory tract infections, particularly in young children. This study investigated the frequency of hMPV and HCoV-NL63 infections in Swedish children by screening 221 nasopharyngeal aspirates, collected between November 2003 and May 2005, from 212 children attending the paediatric department of a county hospital in Sweden or submitted from local general practitioners. The samples were originally submitted to be tested for respiratory syncytial virus (RSV), and were examined retrospectively for hMPV and HCoV-NL63 by RT-PCR. Of the 212 patients, 101 were positive for RSV (48%), 22 (10%) were positive for hMPV, and 12 (6%) were positive for HCoV-NL63. The frequency of HCoV-NL63 infection increased from 1% in 2003-2004 to 10% in 2004-2005. Sequence analysis of parts of the coronavirus genomes showed considerable similarity to the HCoV-NL63 prototype sequence. The study demonstrated that HCoV-NL63 and hMPV occur in south-west Sweden with essentially the same frequency, seasonal distribution and clinical characteristics as have been reported in other countries.

| S-EPMC7128111 | biostudies-literature

Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China.

Project description:BACKGROUND: Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections. RESULTS: Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs. CONCLUSIONS: We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.

| S-EPMC3030507 | biostudies-literature

WU polyomavirus in children with acute lower respiratory tract infections, China.

Project description:BACKGROUND:WU polyomavirus (WUPyV), a new member of the genus of Polyomavirus in the family Polyomaviridae, has been found and associated with respiratory tract infections recently. However, its clinical role and pathogenicity has not been known. OBJECTIVES:To confirm that WU polyomavirus has been found in Chinese children. STUDY DESIGN:WU polyomavirus was detected and identified using PCR methods. A total of 278 specimens of nasopharyngeal aspirate were collected, and then PCR products were sequenced directly. RESULTS:One of 278 nasopharyngeal aspirates was positive for WUPyV in one child, and the positive rate was 0.4%. The results showed that the sequences of genome, LTAg and VP2 gene was identical to the reference sequences of WU polyomavirus prototype strains. CONCLUSIONS:We confirmed that WU polyomavirus had been found and identified in the respiratory secretions in China.

| S-EPMC7108408 | biostudies-literature

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