-
Der Internist Nov 2019Human rhinoviruses (RV) belong to the Picornaviridae and are divided into three species: rhinovirus A, B and C. As causative viruses of upper airway infections... (Review)
Review
Human rhinoviruses (RV) belong to the Picornaviridae and are divided into three species: rhinovirus A, B and C. As causative viruses of upper airway infections (common cold), they possess enormous epidemiological and clinical importance. Furthermore, rhinoviruses are significant pathogens of acute exacerbations of chronic airway diseases such as asthma and chronic obstructive pulmonary disease. Their role as a cofactor in the development of pneumonia and their relevance in critically ill patients is still unclear and the focus of current research. Due to the unspecific clinical symptoms, diagnosis is difficult. Laboratory detection is sophisticated and a distinction between clinically relevant infection and contamination not always possible. Specific therapeutic antiviral strategies against rhinovirus infection do not exist as yet and, due to the large variety of subtypes, the development of vaccines remains a considerable challenge.
Topics: Antiviral Agents; Asthma; Disease Progression; Humans; Picornaviridae Infections; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinitis; Rhinovirus
PubMed: 31463521
DOI: 10.1007/s00108-019-00672-4 -
Journal of Virology Sep 2019The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with very different levels...
The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with very different levels of geographic isolation. Metagenomic analysis was used to characterize viral nucleic acids in nasal swabs from 63 apparently healthy young children. Sequences from human virus members of the families , , , , , , and were detected in decreasing proportions of children. The number of papillomavirus infections detected was greater among Hispanic children most exposed to outside contacts, while anellovirus infections were more common in the isolated indigenous villages. The diversity of the other human viruses detected did not differ among the villages. Closely related variants of rhinovirus A or B were identified in 2 to 4 children from each village, reflecting ongoing transmission clusters. Genomes of viruses not currently known to infect humans, including members of the families , , , and and circular Rep-encoding single-stranded DNA (CRESS-DNA) virus, were also detected in nasal swabs, possibly reflecting environmental contamination from insect, fungal, or unknown sources. Despite the high levels of geographic and cultural isolation, the overall diversity of human viruses in the nasal passages of children was not reduced in highly isolated indigenous villages, indicating ongoing exposure to globally circulating viruses. Extreme geographic and cultural isolation can still be found in some indigenous South American villages. Such isolation may be expected to limit the introduction of otherwise common and widely distributed viruses. Very small population sizes may also result in rapid local viral extinction due to a lack of seronegative subjects to maintain transmission chains for rapidly cleared viruses. We compared the viruses in the nasal passages of young children in three villages with increasing levels of geographic isolation. We found that isolation did not reduce the overall diversity of viral infections. Multiple infections with nearly identical rhinoviruses could be detected within each village, likely reflecting recent viral introductions and transmission clusters among epidemiologically linked members of these very small communities. We conclude that, despite their geographic isolation, remote indigenous villages show evidence of ongoing exposure to globally circulating viruses.
Topics: Biodiversity; Child; Child, Preschool; Colombia; Female; Humans; Indigenous Peoples; Male; Metagenomics; Nose; Phylogeny; Phylogeography; Viruses
PubMed: 31189707
DOI: 10.1128/JVI.00681-19 -
JAMA Pediatrics Jun 2019Rhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging... (Observational Study)
Observational Study
IMPORTANCE
Rhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging evidence links different rhinovirus species (eg, rhinovirus C) to a higher severity of infection and asthma exacerbation, to our knowledge, little is known about longitudinal associations of rhinovirus C infection during infancy with subsequent morbidities.
OBJECTIVE
To examine the association of different viruses (respiratory syncytial virus [RSV], rhinovirus species) in bronchiolitis with risks of developing recurrent wheeze.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter prospective cohort study of infants younger than 1 year who were hospitalized for bronchiolitis was conducted at 17 hospitals across 14 US states during 3 consecutive fall to winter seasons (2011-2014).
EXPOSURES
Major causative viruses of bronchiolitis, including RSV (reference group) and 3 rhinovirus species (rhinovirus A, B, and C).
MAIN OUTCOMES AND MEASURES
Development of recurrent wheeze (as defined in national asthma guidelines) by age 3 years.
RESULTS
This analytic cohort comprised 716 infants who were hospitalized for RSV-only or rhinovirus bronchiolitis. The median age was 2.9 months (interquartile range, 1.6-3.8 months), 541 (76%) had bronchiolitis with RSV only, 85 (12%) had rhinovirus A, 12 (2%) had rhinovirus B, and 78 (11%) had rhinovirus C infection. Overall, 231 (32%) developed recurrent wheeze by age 3 years. In the multivariable Cox model, compared with infants with RSV-only infection, the risk of recurrent wheeze was not significantly different in those with rhinovirus A or B (rhinovirus A: hazard ratio [HR], 1.27; 95% CI, 0.86-1.88; rhinovirus B: HR, 1.39; 95% CI, 0.51-3.77; both P > .10). By contrast, infants with rhinovirus C had a significantly higher risk (HR, 1.58; 95% CI, 1.08-2.32). There was a significant interaction between virus groups and IgE sensitization on the risk of recurrent wheeze (P for interaction < .01). Only infants with both rhinovirus C infection and IgE sensitization (to food or aeroallergens) during infancy had significantly higher risks of recurrent wheeze (HR, 3.03; 95% CI, 1.20-7.61). Furthermore, compared with RSV-only, rhinovirus C infection with IgE sensitization was associated with significantly higher risks of recurrent wheeze with subsequent development of asthma at age 4 years (HR, 4.06; 95% CI, 1.17-14.1).
CONCLUSIONS AND RELEVANCE
This multicenter cohort study of infants hospitalized for bronchiolitis demonstrated between-virus differences in the risk of developing recurrent wheeze. Infants with rhinovirus C infection, along with IgE sensitization, had the highest risk. This finding was driven by the association with a subtype of recurrent wheeze: children with subsequent development of asthma.
Topics: Asthma; Biomarkers; Bronchiolitis, Viral; Child, Preschool; Coxsackievirus Infections; Enterovirus; Female; Follow-Up Studies; Food Hypersensitivity; Humans; Immunoglobulin E; Infant; Male; Proportional Hazards Models; Prospective Studies; Recurrence; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Risk Factors
PubMed: 30933255
DOI: 10.1001/jamapediatrics.2019.0384 -
Brain & Development Jun 2019Rhinovirus is a common respiratory pathogen for children throughout the year; nevertheless, its central nervous system involvement is extremely rare, and only two cases...
BACKGROUND
Rhinovirus is a common respiratory pathogen for children throughout the year; nevertheless, its central nervous system involvement is extremely rare, and only two cases have been reported to date: meningitis and sepsis-like illness.
PATIENT
A previously healthy 2-year-old Japanese boy developed fever, followed by seizures and lethargy. His cerebrospinal fluid cell count and protein level were slightly increased; brain magnetic resonance imaging showed abnormal intensities in the bilateral cerebellar dentate nuclei, which were prominent in diffusion-weighted images. After his consciousness disturbance improved, cerebellar dysfunction became apparent. He was treated symptomatically, without steroids or any other immunosuppressants. He almost recovered within a few months; however, cerebellar atrophy became evident on brain magnetic resonance imaging. Using acute specimens, human rhinovirus A was detected in his throat swab and cerebrospinal fluid.
DISCUSSION
Acute cerebellitis, in which cerebellar inflammation is predominant, is occasionally accompanied by cerebral symptoms, such as consciousness disturbance and seizures. As a causative pathogen, rotavirus is the most common; however, rhinovirus-associated acute encephalitis/encephalopathy and concurrent cerebellitis have not been reported before. Further research, using recent molecular techniques to detect various central nervous system pathogens, including rhinovirus, is needed to delineate the underlying pathophysiology.
Topics: Brain Diseases; Central Nervous System; Cerebellar Diseases; Cerebellum; Child, Preschool; Diffusion Magnetic Resonance Imaging; Encephalitis; Enterovirus; Fever; Humans; Infectious Encephalitis; Japan; Male; Rhinovirus; Rotavirus; Rotavirus Infections; Seizures
PubMed: 30850156
DOI: 10.1016/j.braindev.2019.02.014 -
Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia.PloS One 2018Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with... (Clinical Trial)
Clinical Trial
Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.
Topics: Adolescent; Adult; Aged; Central Nervous System Viral Diseases; Female; Humans; Indonesia; Male; Middle Aged
PubMed: 30444898
DOI: 10.1371/journal.pone.0207440 -
The Journal of Infectious Diseases Jun 2019
Topics: Enterovirus Infections; Humans; Phylogeny; RNA, Viral; Reverse Genetics; Rhinovirus
PubMed: 30383231
DOI: 10.1093/infdis/jiy630 -
Journal of Microbiology, Immunology,... Apr 2019Human rhinovirus (HRV) can cause severe illnesses in hospitalized patients. However, there are no studies regarding the prevalence of HRV infection, particularly the...
BACKGROUND
Human rhinovirus (HRV) can cause severe illnesses in hospitalized patients. However, there are no studies regarding the prevalence of HRV infection, particularly the recently identified HRV-C, in hospitalized patients reported from Taiwan.
METHODS
Respiratory specimens collected from 487 hospitalized patients in designated wards between 2013 and 2014 in a medical center in northern Taiwan were retrospectively detected for HRV. Positive specimens were further determined for genotyping. Medical charts of the HRV-positive patients were reviewed retrospectively.
RESULTS
Totally, 76 patients (15.6%) were HRV positive, of which 60 were pediatric patients. HRV-A was identified in 41 (54%) patients, HRV-B in 6 patients (7.9%) and HRV-C in 29 patients (38%). A total of 47 different genotypes were identified. HRV infections were predominant during fall and winter seasons. 21.1% were affected by HRV alone and 78.9% were found to be co-infected with other microorganisms. The detection rate of HRV in children (18.6%) was significantly higher than in adults (9.6%). Compared with pediatric patients, adult patients were significantly associated with underlying disease, Pneumocystis jirovesii pneumonia co-infection, a diagnosis of pneumonia, fatal outcome, hospital acquisition of HRV, antibiotics administration and requiring intensive care, while pediatric patients were significantly associated with viral co-infection.
CONCLUSIONS
HRV was a common cause of respiratory tract infection in Taiwan, particularly in pediatric patients. Eighty percent of HRV-infected inpatients had other microorganisms co-infection. Adult patients were more likely to be associated with a severe respiratory disease entity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Coinfection; Enterovirus; Female; Genotype; Hospitals; Humans; Infant; Male; Middle Aged; Molecular Epidemiology; Molecular Typing; Picornaviridae Infections; Pneumonia, Pneumocystis; Prevalence; Respiratory Tract Infections; Retrospective Studies; Rhinovirus; Taiwan; Young Adult
PubMed: 30201131
DOI: 10.1016/j.jmii.2018.08.009 -
PLoS Pathogens Aug 2018Protein production, genomic RNA replication, and virion assembly during infection by picornaviruses like human rhinovirus and poliovirus take place in the cytoplasm of...
Protein production, genomic RNA replication, and virion assembly during infection by picornaviruses like human rhinovirus and poliovirus take place in the cytoplasm of infected human cells, making them the quintessential cytoplasmic pathogens. However, a growing body of evidence suggests that picornavirus replication is promoted by a number of host proteins localized normally within the host cell nucleus. To systematically identify such nuclear proteins, we focused on those that appear to re-equilibrate from the nucleus to the cytoplasm during infection of HeLa cells with human rhinovirus via quantitative protein mass spectrometry. Our analysis revealed a highly selective re-equilibration of proteins with known mRNA splicing and transport-related functions over nuclear proteins of all other functional classes. The multifunctional splicing factor proline and glutamine rich (SFPQ) was identified as one such protein. We found that SFPQ is targeted for proteolysis within the nucleus by viral proteinase 3CD/3C, and a fragment of SFPQ was shown to migrate to the cytoplasm at mid-to-late times of infection. Cells knocked down for SFPQ expression showed significantly reduced rhinovirus titers, viral protein production, and viral RNA accumulation, consistent with SFPQ being a pro-viral factor. The SFPQ fragment that moved into the cytoplasm was able to bind rhinovirus RNA either directly or indirectly. We propose that the truncated form of SFPQ promotes viral RNA stability or replication, or virion morphogenesis. More broadly, our findings reveal dramatic changes in protein compartmentalization during human rhinovirus infection, allowing the virus to systematically hijack the functions of proteins not normally found at its cytoplasmic site of replication.
Topics: Active Transport, Cell Nucleus; Cell Nucleus; Cytoplasm; HeLa Cells; Host-Pathogen Interactions; Humans; Nuclear Proteins; PTB-Associated Splicing Factor; Protein Transport; Proteolysis; RNA, Viral; Rhinovirus
PubMed: 30142213
DOI: 10.1371/journal.ppat.1007277 -
JCI Insight Aug 2018Enterovirus D68 (EV-D68) shares biologic features with rhinovirus (RV). In 2014, a nationwide outbreak of EV-D68 was associated with severe asthma-like symptoms. We...
Enterovirus D68 (EV-D68) shares biologic features with rhinovirus (RV). In 2014, a nationwide outbreak of EV-D68 was associated with severe asthma-like symptoms. We sought to develop a mouse model of EV-D68 infection and determine the mechanisms underlying airway disease. BALB/c mice were inoculated intranasally with EV-D68 (2014 isolate), RV-A1B, or sham, alone or in combination with anti-IL-17A or house dust mite (HDM) treatment. Like RV-A1B, lung EV-D68 viral RNA peaked 12 hours after infection. EV-D68 induced airway inflammation, expression of cytokines (TNF-α, IL-6, IL-12b, IL-17A, CXCL1, CXCL2, CXCL10, and CCL2), and airway hyperresponsiveness, which were suppressed by anti-IL-17A antibody. Neutrophilic inflammation and airway responsiveness were significantly higher after EV-D68 compared with RV-A1B infection. Flow cytometry showed increased lineage-, NKp46-, RORγt+ IL-17+ILC3s and γδ T cells in the lungs of EV-D68-treated mice compared with those in RV-treated mice. EV-D68 infection of HDM-exposed mice induced additive or synergistic increases in BAL neutrophils and eosinophils and expression of IL-17, CCL11, IL-5, and Muc5AC. Finally, patients from the 2014 epidemic period with EV-D68 showed significantly higher nasopharyngeal IL-17 mRNA levels compared with patients with RV-A infection. EV-D68 infection induces IL-17-dependent airway inflammation and hyperresponsiveness, which is greater than that generated by RV-A1B, consistent with the clinical picture of severe asthma-like symptoms.
Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cell Line, Tumor; Child; Child, Preschool; Disease Models, Animal; Enterovirus; Enterovirus D, Human; Enterovirus Infections; Female; Humans; Infant; Infant, Newborn; Interleukin-17; Lung; Male; Mice; Nasopharynx; Neutrophils; Pyroglyphidae; RNA, Messenger
PubMed: 30135310
DOI: 10.1172/jci.insight.121882 -
The Pediatric Infectious Disease Journal Mar 2019In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections...
In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections were genotyped. Rhinovirus-A and -C species were predominant in the US study, while rhinovirus-C species was predominant in the Finland study. In both cohorts, there were no significant between-species differences in clinical characteristics, including acute severity measures.
Topics: Bronchiolitis, Viral; Female; Finland; Hospitalization; Humans; Infant; Male; Molecular Typing; Picornaviridae Infections; Prospective Studies; Rhinovirus; Severity of Illness Index; United States
PubMed: 30001231
DOI: 10.1097/INF.0000000000002141