Human metapneumovirus and severity of respiratory syncytial virus disease.
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ABSTRACT:
SUBMITTER: Lazar I
PROVIDER: S-EPMC3323339 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Reverse transcription-polymerase chain reaction was used to detect segments of the M (matrix), N (nucleoprotein), and F (fusion) genes of human metapneumovirus in bronchoalveolar fluid from 30 infants with severe respiratory syncytial virus bronchiolitis. Seventy percent of them were coinfected with metapneumovirus. Such coinfection might be a factor influencing the severity of bronchiolitis.
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Project description:Respiratory viral infections due to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause infections in immunocompromised transplant patients ranging from mild upper respiratory infections to severe lower respiratory tract disease with respiratory failure. These viruses are more readily diagnosed due to improvements in sensitive molecular diagnostic methods. The epidemiology of RSV and hMPV is similarly becoming more readily appreciated in hematopoietic stem cell transplant (HSCT) patients of all ages as well as solid organ transplant (SOT) patients, with lung transplant recipients having evidence of more frequent and severe complications related to these viruses. RSV and hMPV infection typically but not always present with upper respiratory signs and symptoms that progress to lower respiratory tract disease. Treatment options for RSV are limited, with aerosolized, intravenous, and oral ribavirin all studied in HSCT and lung transplant patients. No antiviral therapy for the treatment of hMPV is available, although ribavirin has shown some effectiveness in vitro. New antiviral agents including RSV fusion inhibitors and nucleoside analogs are being developed, with some under clinical evaluation.
| S-EPMC7123147 | biostudies-literature
Project description:Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse attachment (G) glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.
| S-EPMC3046979 | biostudies-literature
Project description:Children and adults residing in densely populated urban centers around the world are at risk of seasonal influenza-like illness caused by respiratory viruses such as influenza virus, human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). In a large metropolitan of Thailand's capital city Bangkok, most respiratory infections are rarely confirmed by molecular diagnostics. We therefore examined the frequency of RSV, hMPV, and influenza virus in 8,842 patients who presented influenza-like illness and sought medical care at a large hospital in Bangkok between 2016 and 2017. Using a multiplex real-time reverse-transcription polymerase chain reaction (RT-PCR), 30.5% (2,699/8,842) of nasopharyngeal (NP) swab samples tested positive for one or more of these viruses. Influenza virus comprised 17.3% (1,528/8,842), of which the majority were influenza A/H3N2. Such infection was most prevalent among adults and the elderly. RSV was identified in 11.4% (1,011/8,842) and were mostly ON1 and BA9 genotypes. Of the hMPV-positive samples (3.6%, 318/8,842), genotypes A2, B1, and B2 were detected. A small number of individuals experienced co-infections (1.8%, 155/8,842), most commonly between RSV and influenza A/H3N2. RSV and hMPV co-infections were also found, but mainly in young children. Viral respiratory tract infection peaked locally in the rainy season (June to September). These findings support the utility of rapid nucleic acid testing of RSV, hMPV, and influenza virus in patients with ILI.
| S-EPMC6462397 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs) in children worldwide and can cause high mortality, especially in developing countries. However, information on the clinical and molecular characteristics of RSV infection in developing countries is limited. From April 2010 to May 2011, 1,082 nasopharyngeal swabs were collected from children with ARI admitted to the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for RSV and genotyped by reverse transcription-PCR and sequencing. Demographic and clinical data was also recorded. RSV was found in 23.8% (257/1,082) of samples. RSV A was the dominant subgroup, accounting for 91.4% (235/257), followed by RSV B, 5.1% (13/257), and 9 cases (3.5%) were mixed infection of these subgroups. The phylogenetic analysis revealed that all group A strains belonged to the GA2 genotype. All group B strains belonged to the recently identified BA genotype, and further clustered into 2 recently described subgenotypes BA9 and BA10. One GA2 genotype strain had a premature stop codon which shortened the G protein length. RSV infection was significantly associated with younger age and higher severity score than those without. Co-infection with other viruses did not affect disease severity. RSV A caused more severe disease than RSV B. The results from this study will not only contribute to the growing database on the molecular diversity of RSV circulating worldwide but may be also useful in clinical management and vaccine development.
| S-EPMC3551923 | biostudies-literature
Project description:Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥ 4-fold increase in titers of antibody to hRSV, 24 (25.8%) showed a concurrent increase in titers of antibody to hMPV; of 91 pairs showing an increase to hMPV, 13 (14.3%) showed a concurrent increase to hRSV. We speculated that common antigens shared by these viruses explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared for each virus against baculovirus-expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blotting, this truncated protein did not react with hMPV IgG-positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared for this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region.
| S-EPMC4400756 | biostudies-literature
Project description:BackgroundIt is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV).MethodsWe prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped.ResultsA total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12-23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease.ConclusionsAmong hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.
| S-EPMC5240941 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two closely related viruses that cause bronchiolitis and pneumonia in infants and the elderly1, with a significant health burden2-6. There are no licensed vaccines or small-molecule antiviral treatments specific to these two viruses at present. A humanized murine monoclonal antibody (palivizumab) is approved to treat high-risk infants for RSV infection7,8, but other treatments, as well as vaccines, for both viruses are still in development. Recent epidemiological modelling suggests that cross-immunity between RSV, HMPV and human parainfluenzaviruses may contribute to their periodic outbreaks9, suggesting that a deeper understanding of host immunity to these viruses may lead to enhanced strategies for their control. Cross-reactive neutralizing antibodies to the RSV and HMPV fusion (F) proteins have been identified10,11. Here, we examine the structural basis for cross-reactive antibody binding to RSV and HMPV F protein by two related, independently isolated antibodies, MPE8 and 25P13. We solved the structure of the MPE8 antibody bound to RSV F protein and identified the 25P13 antibody from an independent blood donor. Our results indicate that both antibodies use germline residues to interact with a conserved surface on F protein that could guide the emergence of cross-reactivity. The induction of similar cross-reactive neutralizing antibodies using structural vaccinology approaches could enhance intrinsic cross-immunity to these paramyxoviruses and approaches to controlling recurring outbreaks.
| S-EPMC5308794 | biostudies-literature
Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
2018-03-21 | GSE103842 | GEO
Project description:Background. Human Metapneumovirus (HMPV) and Respiratory Syncytial Virus (RSV), are responsible for respiratory diseases mostly in children. In spite of the resemblance between these two pneumoviruses, they elicit a different extent of immune response. miRNAs are small non coding RNAs that regulate gene expression and are involved in numerous cellular processes including the immune system. Methodology. Human monocyte-derived dendritic cells (moDC) were differentiated from peripheral blood mononuclear cells and infected at an MOI of 3 for 24h. RNA was isolated to analyze the miRNAs transcription by high throughput sequencing using illumina technology. Principal findings. Infection with HMPV up-regulated the expression of hsa-miR-4448, while RSV infection induced significant expression of hsa-miR-30a-5p, hsa-miR-182-5p, hsa-miR-1913, hsa37, miR-4448 and hsa-miR-4634. Conclusions/Significance. In human monocyte derived dendritic cells (moDC), RSV and HMPV induced different profiles of miRNA expression. Understanding the changes of miRNA expression profiles by RSV and HMPV in immune cells will further our understanding of the differential immune response induced by these respiratory viruses
2018-12-10 | GSE111732 | GEO