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1.
Sci Rep ; 14(1): 10431, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714841

ABSTRACT

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.


Subject(s)
Common Cold , Pan troglodytes , Animals , Humans , Child , Female , Male , Child, Preschool , Common Cold/epidemiology , Common Cold/virology , Adult , Uganda/epidemiology , Prospective Studies , Zoonoses/epidemiology , Zoonoses/virology , COVID-19/epidemiology , COVID-19/virology , COVID-19/transmission , Ape Diseases/epidemiology , Ape Diseases/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/veterinary , Rhinovirus/isolation & purification , Rhinovirus/genetics , SARS-CoV-2/isolation & purification , Incidence
2.
J Gen Virol ; 105(5)2024 May.
Article in English | MEDLINE | ID: mdl-38717926

ABSTRACT

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.


Subject(s)
COVID-19 , Respiratory Tract Infections , SARS-CoV-2 , Seasons , Humans , Female , Male , COVID-19/epidemiology , COVID-19/virology , Child, Preschool , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Infant , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Child , Rhinovirus/isolation & purification , Rhinovirus/genetics , Nasopharynx/virology , Adolescent , Influenza, Human/epidemiology , Influenza, Human/virology , Pandemics , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology
3.
Front Cell Infect Microbiol ; 14: 1380855, 2024.
Article in English | MEDLINE | ID: mdl-38803572

ABSTRACT

Introduction: Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables. Materials and methods: Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV. Results: The risks of viral codetection were 4.1 (IC95[1.8; 10.0]) and 93.9 1 (IC95[48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02). Conclusions: Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome.


Subject(s)
Coinfection , Respiratory Tract Infections , Rhinovirus , Viral Load , Humans , Coinfection/virology , Infant , Respiratory Tract Infections/virology , Female , Child, Preschool , Male , Rhinovirus/isolation & purification , Rhinovirus/genetics , Child , Health Status , Adult , Respiratory Syncytial Virus Infections/virology , Adolescent , Middle Aged , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/isolation & purification , Nasopharynx/virology , Infant, Newborn , Young Adult , Aged , Real-Time Polymerase Chain Reaction , Acute Disease , Genotype , Multiplex Polymerase Chain Reaction , Aged, 80 and over
4.
Viruses ; 16(5)2024 04 28.
Article in English | MEDLINE | ID: mdl-38793579

ABSTRACT

Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country.


Subject(s)
COVID-19 , Genetic Variation , Phylogeny , Respiratory Tract Infections , Humans , Gabon/epidemiology , COVID-19/epidemiology , COVID-19/virology , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , SARS-CoV-2/genetics , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Male , Adult , Female , Child , Middle Aged , Adolescent , Child, Preschool , Young Adult , Rhinovirus/genetics , Rhinovirus/isolation & purification , Rhinovirus/classification , Viruses/genetics , Viruses/classification , Viruses/isolation & purification , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Metapneumovirus/classification , Genome, Viral , Nasopharynx/virology , Infant , Aged , Pandemics , Influenza A virus/genetics , Influenza A virus/isolation & purification , Influenza A virus/classification
5.
J Med Virol ; 96(4): e29582, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38590253

ABSTRACT

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.


Subject(s)
Enterovirus Infections , Picornaviridae Infections , Respiratory Tract Infections , Child , Humans , Infant , Child, Preschool , Aged , Rhinovirus/genetics , Prevalence , Picornaviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , China/epidemiology , Genetic Variation
6.
Viruses ; 16(4)2024 03 30.
Article in English | MEDLINE | ID: mdl-38675883

ABSTRACT

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.


Subject(s)
Coinfection , Disease Outbreaks , Metapneumovirus , Molecular Epidemiology , Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Humans , China/epidemiology , Coinfection/epidemiology , Coinfection/virology , Male , Child, Preschool , Female , Child , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Genotype , Rhinovirus/genetics , Rhinovirus/isolation & purification , Rhinovirus/classification , Phylogeny , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/virology , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/isolation & purification , Schools
7.
Pharm. pract. (Granada, Internet) ; 22(1): 1-11, Ene-Mar, 2024.
Article in English | IBECS | ID: ibc-231359

ABSTRACT

Human rhinoviruses (HRVs) are associated with a wide spectrum of clinical manifestations, ranging from mild cold symptoms to more severe respiratory illnesses, significantly burdening global healthcare systems. At the molecular level, HRVs belong to the Picornaviridae family and are classified into three species: HRV-A, HRV-B, and HRV-C. Advances in genomic sequencing and phylogenetic analysis have revealed a remarkable genetic diversity within HRV species, with over 160 serotypes identified. This genetic variability contributes to the ability of HRVs to evade host immune responses and facilitates their continuous circulation in the population. This review provides an overview of the molecular and clinical aspects of HRV infections.(AU)


Subject(s)
Humans , Rhinovirus/genetics , Rhinovirus/classification , Respiratory Tract Diseases/drug therapy , Genome/genetics , Picornaviridae/genetics , Picornaviridae Infections/microbiology
8.
Front Immunol ; 15: 1330991, 2024.
Article in English | MEDLINE | ID: mdl-38410509

ABSTRACT

Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35th Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., Haemophilus influenzae, Moraxella catarrhalis, Moraxella nonliquefaciens, and Streptococcus pneumoniae). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.


Subject(s)
Bronchiolitis , Enterovirus Infections , MicroRNAs , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Viruses , Infant , Humans , Rhinovirus/genetics , RNA, Bacterial , Bronchiolitis/genetics , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus Infections/genetics , Immunity
9.
J Pediatric Infect Dis Soc ; 13(3): 189-195, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38366142

ABSTRACT

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by polymerase chain reaction (PCR) in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting ≥4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with ≥70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of respiratory syncytial virus (RSV) A infections, and 7% of RSV B infections. No prolonged detection was found for influenza virus A or B, coronavirus 229E or HKU1, and parainfluenza virus 2 or 4 infections. First-lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virus Diseases , Viruses , Child , Humans , Infant , Birth Cohort , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Viruses/genetics , Rhinovirus/genetics , Respiratory Syncytial Virus, Human/genetics , Polymerase Chain Reaction
10.
Antimicrob Agents Chemother ; 68(3): e0106423, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38349161

ABSTRACT

Screening a library of 1,200 preselected kinase inhibitors for anti-human rhinovirus 2 (HRV-2) activity in HeLa cells identified a class of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) as effective virus blockers. These were based on the 4-anilinoquinazoline-7-oxypiperidine scaffold, with the most potent representative AZ5385 inhibiting the virus with EC50 of 0.35 µM. Several structurally related analogs confirmed activity in the low µM range, while interestingly, other TKIs targeting EGFR lacked anti-HRV-2 activity. To further probe this lack of association between antiviral activity and EGFR inhibition, we stained infected cells with antibodies specific for activated EGFR (Y1068) and did not observe a dependency on EGFR-TK activity. Instead, consecutive passages of HRV-2 in HeLa cells in the presence of a compound and subsequent nucleotide sequence analysis of resistant viral variants identified the S181T and T210A alterations in the major capsid VP1 protein, with both residues located in the vicinity of a known hydrophobic pocket on the viral capsid. Further characterization of the antiviral effects of AZ5385 showed a modest virus-inactivating (virucidal) activity, while anti-HRV-2 activity was still evident when the inhibitor was added as late as 10 h post infection. The RNA copy/infectivity ratio of HRV-2 propagated in AZ5385 presence was substantially higher than that of control HRV indicating that the compound preferentially targeted HRV progeny virions during their maturation in infected cells. Besides HRV, the compound showed anti-respiratory syncytial virus activity, which warrants its further studies as a candidate compound against viral respiratory infections.


Subject(s)
Rhinovirus , Humans , Rhinovirus/chemistry , Rhinovirus/genetics , HeLa Cells , Capsid Proteins , Antiviral Agents/chemistry , ErbB Receptors
11.
Antiviral Res ; 222: 105810, 2024 02.
Article in English | MEDLINE | ID: mdl-38244889

ABSTRACT

Rhinoviruses (RVs) cause the common cold. Attempts at discovering small molecule inhibitors have mainly concentrated on compounds supplanting the medium chain fatty acids residing in the sixty icosahedral symmetry-related hydrophobic pockets of the viral capsid of the Rhinovirus-A and -B species. High-affinity binding to these pockets stabilizes the capsid against structural changes necessary for the release of the ss(+) RNA genome into the cytosol of the host cell. However, single-point mutations may abolish this binding. RV-B5 is one of several RVs that are naturally resistant against the well-established antiviral agent pleconaril. However, RV-B5 is strongly inhibited by the pyrazolopyrimidine OBR-5-340. Here, we report on isolation and characterization of RV-B5 mutants escaping OBR-5-340 inhibition and show that substitution of amino acid residues not only within the binding pocket but also remote from the binding pocket hamper inhibition. Molecular dynamics network analysis revealed that strong inhibition occurs when an ensemble of several sequence stretches of the capsid proteins enveloping OBR-5-340 move together with OBR-5-340. Mutations abrogating this dynamic, regardless of whether being localized within the binding pocket or distant from it result in escape from inhibition. Pyrazolo [3,4-d]pyrimidine derivatives overcoming OBR-5-340 escape of various RV-B5 mutants were identified. Our work contributes to the understanding of the properties of capsid-binding inhibitors necessary for potent and broad-spectrum inhibition of RVs.


Subject(s)
Capsid Proteins , Enterovirus Infections , Humans , Capsid Proteins/metabolism , Capsid/metabolism , Rhinovirus/genetics , Binding Sites , Enterovirus Infections/metabolism , Molecular Dynamics Simulation , Mutation , Antiviral Agents/chemistry
12.
J Infect Dis ; 229(2): 403-412, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-37486790

ABSTRACT

BACKGROUND: Rhinovirus (RV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how RV evolves within hosts during infection. METHODS: We sequenced RV complete genomes from 12 hematopoietic cell transplant patients with infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL). Metagenomic and amplicon next-generation sequencing were used to track the emergence and evolution of intrahost single nucleotide variants (iSNVs). RESULTS: Identical RV intrahost populations in matched NW and BAL specimens indicated no genetic adaptation is required for RV to progress from URT to LRT. Coding iSNVs were 2.3-fold more prevalent in capsid over nonstructural genes. iSNVs modeled were significantly more likely to be found in capsid surface residues, but were not preferentially located in known RV-neutralizing antibody epitopes. Newly emergent, genotype-matched iSNV haplotypes from immunocompromised individuals in 2008-2010 could be detected in Seattle-area community RV sequences in 2020-2021. CONCLUSIONS: RV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, RV sequences.


Subject(s)
Enterovirus Infections , Hematopoietic Stem Cell Transplantation , Humans , Capsid Proteins/genetics , Capsid , Rhinovirus/genetics , Mutation
13.
Am J Infect Control ; 52(4): 472-478, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37972820

ABSTRACT

BACKGROUND: While airborne transmission of rhinovirus is recognized in indoor settings, its role in hospital transmission remains unclear. METHODS: We investigated an outbreak of rhinovirus in a pediatric intensive care unit (PICU) to assess air dispersal. We collected clinical, environmental, and air samples, and staff's surgical masks for viral load and phylogenetic analysis. Hand hygiene compliance and the number of air changes per hour in the PICU were measured. A case-control analysis was performed to identify nosocomial rhinovirus risk factors. RESULTS: Between March 31, 2023, and April 2, 2023, three patients acquired rhinovirus in a cubicle (air changes per hour: 14) of 12-bed PICU. A portable air-cleaning unit was placed promptly. Air samples (72,000 L in 6 hours) from the cohort area, and outer surfaces of staff's masks (n = 8), were rhinovirus RNA-negative. Hand hygiene compliance showed no significant differences (31/34, 91.2% vs 33/37, 89.2%, P = 1) before and during outbreak. Only 1 environmental sample (3.8%) was positive (1.86 × 103 copies/mL). Case-control and next-generation sequencing analysis implicated an infected staff member as the source. CONCLUSIONS: Our findings suggest that air dispersal of rhinovirus was not documented in the well-ventilated PICU during the outbreak. Further research is needed to better understand the dynamics of rhinovirus transmission in health care settings.


Subject(s)
Disease Outbreaks , Rhinovirus , Child , Humans , Rhinovirus/genetics , Phylogeny , Disease Outbreaks/prevention & control , Intensive Care Units, Pediatric
14.
Nucleic Acids Res ; 52(D1): D770-D776, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37930838

ABSTRACT

Rhinovirus (RV), a prominent causative agent of both upper and lower respiratory diseases, ranks among the most prevalent human respiratory viruses. RV infections are associated with various illnesses, including colds, asthma exacerbations, croup and pneumonia, imposing significant and extended societal burdens. Characterized by a high mutation rate and genomic diversity, RV displays a diverse serological landscape, encompassing a total of 174 serotypes identified to date. Understanding RV genetic diversity is crucial for epidemiological surveillance and investigation of respiratory diseases. This study introduces a comprehensive and high-quality RV data resource, designated RVdb (http://rvdb.mgc.ac.cn), covering 26 909 currently identified RV strains, along with RV-related sequences, 3D protein structures and publications. Furthermore, this resource features a suite of web-based utilities optimized for easy browsing and searching, as well as automatic sequence annotation, multiple sequence alignment (MSA), phylogenetic tree construction, RVdb BLAST and a serotyping pipeline. Equipped with a user-friendly interface and integrated online bioinformatics tools, RVdb provides a convenient and powerful platform on which to analyse the genetic characteristics of RVs. Additionally, RVdb also supports the efforts of virologists and epidemiologists to monitor and trace both existing and emerging RV-related infectious conditions in a public health context.


Subject(s)
Asthma , Enterovirus Infections , Picornaviridae Infections , Rhinovirus , Humans , Genomics , Phylogeny , Picornaviridae Infections/genetics , Rhinovirus/genetics
15.
Small ; 20(6): e2304722, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37806749

ABSTRACT

Infection of humans by many viruses is typically initiated by the internalization of a single virion in each of a few susceptible cells. Thus, the outcome of the infection process may depend on stochastic single-molecule events. A crucial process for viral infection, and thus a target for developing antiviral drugs, is the uncoating of the viral genome. Here a force spectroscopy procedure using an atomic force microscope is implemented to study uncoating for individual human rhinovirus particles. Application of an increasing mechanical force on a virion led to a high force-induced structural transition that facilitated extrusion of the viral RNA molecule without loss of capsid integrity. Application of force to virions that h ad previously extruded the RNA, or to RNA-free capsids, led to a lower force-induced event associated with capsid disruption. The kinetic parameters are determined for each reaction. The high-force event is a stochastic process governed by a moderate free energy barrier (≈20 kcal mol-1 ), which results in a heterogeneous population of structurally weakened virions in which different fractions of the RNA molecule are externalized. The effects of antiviral compounds or capsid mutation on the kinetics of this reaction reveal a correlation between the reaction rate and virus infectivity.


Subject(s)
Capsid Proteins , Rhinovirus , Humans , Rhinovirus/genetics , Capsid/chemistry , RNA, Viral/genetics , Antiviral Agents/pharmacology , Virion
16.
J Infect Dis ; 229(2): 422-431, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-37531658

ABSTRACT

BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.


Subject(s)
Enterovirus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virus Diseases , Viruses , Humans , Infant , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Washington/epidemiology , Viruses/genetics , Rhinovirus/genetics
17.
Genes (Basel) ; 14(12)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38137032

ABSTRACT

The human rhinovirus (RV) is a positive-stranded RNA virus that causes respiratory tract diseases affecting both the upper and lower halves of the respiratory system. RV enhances its replication by concentrating RNA synthesis within a modified host membrane in an intracellular compartment. RV infections often occur alongside infections caused by other respiratory viruses, and the RV virus may remain asymptomatic for extended periods. Alongside qualitative detection, it is essential to accurately quantify RV RNA from clinical samples to explore the relationships between RV viral load, infections caused by the virus, and the resulting symptoms observed in patients. A reference material (RM) is required for quality evaluation, the performance evaluation of molecular diagnostic products, and evaluation of antiviral agents in the laboratory. The preparation process for the RM involves creating an RV RNA mixture by combining RV viral RNA with RNA storage solution and matrix. The resulting RV RNA mixture is scaled up to a volume of 25 mL, then dispensed at 100 µL per vial and stored at -80 °C. The process of measuring the stability and homogeneity of RV RMs was conducted by employing reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Digital PCR is useful for the analysis of standards and can help to improve measurement compatibility: it represents the equivalence of a series of outcomes for reference materials and samples being analyzed when a few measurement procedures are employed, enabling objective comparisons between quantitative findings obtained through various experiments. The number of copies value represents a measured result of approximately 1.6 × 105 copies/µL. The RM has about an 11% bottle-to-bottle homogeneity and shows stable results for 1 week at temperatures of 4 °C and -20 °C and for 12 months at a temperature of -80 °C. The developed RM can enhance the dependability of RV molecular tests by providing a precise reference value for the absolute copy number of a viral target gene. Additionally, it can serve as a reference for diverse studies.


Subject(s)
Respiratory System , Rhinovirus , Humans , Rhinovirus/genetics , Polymerase Chain Reaction , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , RNA, Viral/analysis
18.
Microbiol Spectr ; 11(6): e0084023, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37733296

ABSTRACT

IMPORTANCE: Based on clinical samples collected in China, we detected and reported 22 types for the first time in China, as well as three types for the first time in Asia, and reported their genetic characteristics and diversity. We identified a novel type of Rhinovirus (RV), A110, highlighting its unique genetic features. We annotated the genomic structure and serotype of all the existing RV sequences in the database, and four novel RV types were identified and their genetic diversity reported. Combined with the sequence annotation, we constructed a complete VP1 data set of RV and conducted the first large-scale evolutionary dynamics analysis of RV. Based on a high-quality data set, we conducted a comprehensive analysis of the guanine-cytosine (GC) content variations among serotypes of RVs. This study provides crucial theoretical support and valuable data for understanding RV's genetic diversity and developing antiviral strategies.


Subject(s)
Enterovirus Infections , Picornaviridae Infections , Humans , Rhinovirus/genetics , Genomics , Phylogeny , Genetic Variation , Picornaviridae Infections/epidemiology
19.
Sci Rep ; 13(1): 12511, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37532756

ABSTRACT

Respiratory viruses that were suppressed through previous lockdowns during the COVID-19 pandemic have recently started to co-circulate with SARS-CoV-2. Understanding the clinical characteristics and symptomatology of different respiratory viral infections can help address the challenges related to the identification of cases and the understanding of SARS-CoV-2 variants' evolutionary patterns. Flu Watch (2006-2011) and Virus Watch (2020-2022) are household community cohort studies monitoring the epidemiology of influenza, respiratory syncytial virus, rhinovirus, seasonal coronavirus, and SARS-CoV-2, in England and Wales. This study describes and compares the proportion of symptoms reported during illnesses infected by common respiratory viruses. The SARS-CoV-2 symptom profile increasingly resembles that of other respiratory viruses as new strains emerge. Increased cough, sore throat, runny nose, and sneezing are associated with the emergence of the Omicron strains. As SARS-CoV-2 becomes endemic, monitoring the evolution of its symptomatology associated with new variants will be critical for clinical surveillance.


Subject(s)
COVID-19 , Enterovirus Infections , Influenza, Human , Respiratory Syncytial Virus, Human , Humans , SARS-CoV-2/genetics , Rhinovirus/genetics , Influenza, Human/epidemiology , Pandemics , Seasons , COVID-19/epidemiology , Communicable Disease Control
20.
J Clin Virol ; 166: 105555, 2023 09.
Article in English | MEDLINE | ID: mdl-37536014

ABSTRACT

BACKGROUND: Rhinovirus (HRV) is a significant seasonal pathogen in children. The emergence of SARS-CoV2, and the social restrictions introduced in, disrupted viral epidemiology. Here we describe the experience of Great Ormond Street Hospital (GOSH), where HRV almost entirely disappeared from the paediatric intensive care units (PICU) during the first national lockdown and then rapidly re-emerged with a fast-increasing incidence, leading to concerns about possible nosocomial transmission in a vulnerable population. OBJECTIVES: To describe alterations in HRV infection amongst PICU patients at GOSH since the emergence of SARS-COV2 STUDY DESIGN: 10,950 nasopharyngeal aspirate viral PCR samples from GOSH PICU patients from 2019 to 2023 were included. 3083 returned a positive result for a respiratory virus, with 1530 samples positive for HRV. 66 HRV isolates from August 2020 - Jan 2021, the period of rapidly increasing HRV incidence, were sequenced. Electronic health record data was retrospectively collected for the same period. RESULTS: Following a reduction in the incidence of HRV infection during the first national lockdown, multiple genotypes of HRV emerged amongst GOSH PICU patients, with the incidence of HRV infection rapidly surging to levels higher than that seen prior to the emergence of SARS-CoV2 and continuing to circulate at increased incidence year-round. CONCLUSIONS: The incidence of HRV infection amongst GOSH PICU patients is markedly higher than prior to the emergence of SARS-CoV2, a pattern not seen in other respiratory viruses. The increased burden of HRV-infection in vulnerable PICU patients has both clinical and infection prevention and control Implications.


Subject(s)
COVID-19 , Enterovirus Infections , Picornaviridae Infections , Respiratory Tract Infections , Child , Humans , Infant , Prevalence , RNA, Viral/genetics , Rhinovirus/genetics , Picornaviridae Infections/epidemiology , Pandemics , Retrospective Studies , COVID-19/epidemiology , SARS-CoV-2/genetics , Communicable Disease Control , Enterovirus Infections/epidemiology , Critical Care
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