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MSphere Jan 2024Human metapneumovirus (HMPV) is a negative-sense single-stranded RNA virus in the family and a leading cause of acute upper and lower respiratory infections,...
Human metapneumovirus (HMPV) is a negative-sense single-stranded RNA virus in the family and a leading cause of acute upper and lower respiratory infections, particularly in children, immunocompromised patients, and the elderly. Although nearly every person is infected with HMPV during early childhood, re-infections occur often, highlighting difficulty in building long-term immunity. Inflammatory responses, including PD-1-mediated impairment of virus-specific CD8 T cells (T), contribute to HMPV disease severity. HMPV strains are divided into four lineages: A1, A2, B1, and B2. However, little is known about immune responses to different viral subtypes. Here, we characterize responses to four HMPV clinical isolates-TN/94-344 (A1), TN/94-49 (A2), C2-202 (B1), and TN/96-35 (B2)- in C57BL/6 (B6) mice. TN/94-49 was avirulent, while TN/94-344, C2-202, and TN/96-35 showed varying degrees of weight loss and clinical disease. Differences in disease did not correlate to virus burden in upper or lower tracts. TN/94-49 HMPV exhibited highest nose titers and delayed lung clearance. Cytokine profiles differed between HMPV isolates, with TN/96-35 inducing the broadest lung inflammatory cytokines. TN/96-35 also showed lower HMPV burden and less weight loss than other virulent isolates, suggesting a more efficient antiviral response. Interestingly, disease correlated with higher expression of T-cell chemoattractant CXCL9. All isolates elicited PD-1 upregulation and decreased IFNγ and CD107a expression in virus-specific T, with little difference between HMPV subtypes. This work uncovers previously uncharacterized variations in immune responses to clinical HMPV isolates of different lineages.IMPORTANCEThis study extensively explored differences in T-cell-mediated immunity between human metapneumovirus (HMPV) clinical isolates. Much existing HMPV research has been done with strains passaged extensively in cell lines, likely acquiring mutations advantageous to replication. Clinical isolates are collected directly from human patients and have undergone <10 passages, serving as more physiologically relevant models of HMPV infection. Additionally, existing animal studies of HMPV disease mainly focus on lung pathogenesis, while HMPV infects both upper and lower airways of humans. This work highlights distinct differences in HMPV burden in upper and lower tracts between clinical isolates. Lastly, this study uniquely explores differences in host immunity between all four HMPV genetic lineages. The predominant HMPV subtype in circulation varies seasonally; thus, understanding host responses to all subgroups is critical for developing effective HMPV vaccines.
Topics: Child, Preschool; Child; Humans; Mice; Animals; Aged; Metapneumovirus; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Mice, Inbred C57BL; Lung; Weight Loss
PubMed: 38197640
DOI: 10.1128/msphere.00570-23 -
Tidsskrift For Den Norske Laegeforening... Oct 2005Human metapneumovirus (hMPV) is a pathogenic respiratory virus, discovered in 2001. The virus is part of the family paramyxoviridae and is comparatively closely related... (Review)
Review
Human metapneumovirus (hMPV) is a pathogenic respiratory virus, discovered in 2001. The virus is part of the family paramyxoviridae and is comparatively closely related to respiratory syncytial virus (RSV). The clinical manifestations of a hMPV infection are rather similar to infections caused by RSV, ranging from mild upper airway disease to severe pneumonia. Detection of hMPV RNA by polymerase chain reaction (PCR) is the only established routine diagnostic method. The virus is easily cultivated in several types of cell culture lines, however, cell pathology (cytopathic effect) is irregularly observed. Our department has developed an indirect immunofluorescence test based on polyvalent rabbit antibodies. This method appears to give reliable results, detecting hMPV both in cell culture and directly on patient samples. Nasopharyngeal aspirate is the preferred material for diagnostic purposes in small children. A nasopharyngeal swab, or alternatively a throat swab, can be used for older children and adults. Samples from lower airways are appropriate under special circumstances. Serology is not available for routine diagnostic use.
Topics: Adult; Animals; Child; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Polymerase Chain Reaction; Rabbits; Respiratory Tract Infections
PubMed: 16244676
DOI: No ID Found -
Zhongguo Dang Dai Er Ke Za Zhi =... May 2014Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar... (Review)
Review
Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors (TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics may be helpful for developing attenuated live vaccines.
Topics: Humans; Metapneumovirus; Paramyxoviridae Infections; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines
PubMed: 24857012
DOI: No ID Found -
Current Opinion in Biotechnology Dec 2003Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some... (Review)
Review
Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus and Ebola virus. Research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents. More attention needs to be given to the identification of the underlying causes for the emergence of infectious diseases, which are often related to anthropogenic social and environmental changes. Addressing these factors might help to decrease the rate of emergence of infectious diseases and allow the transition to a more sustainable society.
Topics: Animals; Communicable Diseases, Emerging; Ebolavirus; Humans; Influenza A virus; Metapneumovirus; Severe acute respiratory syndrome-related coronavirus; Virus Diseases; West Nile virus
PubMed: 14662395
DOI: 10.1016/j.copbio.2003.10.010 -
Current Opinion in Pharmacology Oct 2007With the recent advances in molecular biology and the ability to amplify viral genomes in a non-sequence-dependent manner, several previously unidentified human... (Review)
Review
With the recent advances in molecular biology and the ability to amplify viral genomes in a non-sequence-dependent manner, several previously unidentified human respiratory viruses have been discovered. There are accumulating data that some of these new pathogens are responsible for a substantial proportion of respiratory tract diseases, particularly in children. This review will focus on several of these newly identified pathogens for which there are clinical data implicating a role of these viruses in respiratory tract disease specifically, human metapneumovirus, human coronaviruses NL63 and HKU1, and the human bocavirus. Antivirals and effective vaccines for these new agents may decrease the burden of respiratory tract diseases.
Topics: Bocavirus; Coronavirus; Humans; Metapneumovirus; Respiratory Tract Infections; Virus Diseases
PubMed: 17689145
DOI: 10.1016/j.coph.2007.07.004 -
Influenza and Other Respiratory Viruses Jul 2018The transmission dynamics of human metapneumovirus (HMPV) in tropical countries remain unclear. Further understanding of the genetic diversity of the virus could aid in...
BACKGROUND
The transmission dynamics of human metapneumovirus (HMPV) in tropical countries remain unclear. Further understanding of the genetic diversity of the virus could aid in HMPV vaccine design and improve our understanding of respiratory virus transmission dynamics in low- and middle-income countries.
MATERIALS & METHODS
We examined the evolution of HMPV in Peru through phylogenetic analysis of 61 full genome HMPV sequences collected in three ecologically diverse regions of Peru (Lima, Piura, and Iquitos) during 2008-2012, comprising the largest data set of HMPV whole genomes sequenced from any tropical country to date.
RESULTS
We revealed extensive genetic diversity generated by frequent viral introductions, with little evidence of local persistence. While considerable viral traffic between non-Peruvian countries and Peru was observed, HMPV epidemics in Peruvian locales were more frequently epidemiologically linked with other sites within Peru. We showed that Iquitos experienced greater HMPV traffic than the similar sized city of Piura by both Bayesian and maximum likelihood methods.
CONCLUSIONS
There is extensive HMPV genetic diversity even within smaller and relatively less connected cities of Peru and this virus is spatially fluid. Greater diversity of HMPV in Iquitos compared to Piura may relate to higher volumes of human movement, including air traffic to this location.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Genetic Variation; Genome, Viral; Humans; Infant; Male; Metapneumovirus; Middle Aged; Paramyxoviridae Infections; Peru; Young Adult
PubMed: 29288526
DOI: 10.1111/irv.12537 -
Viruses Jun 2020The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections,... (Review)
Review
The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.
Topics: Animals; Humans; Immunity, Innate; Killer Cells, Natural; Metapneumovirus; Neutrophils; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32545470
DOI: 10.3390/v12060637 -
Scientific Reports Sep 2023Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We...
Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We conducted an ARI surveillance targeting hospitalized children aged 1 month to 14 years in Nha Trang, Vietnam. Nasopharyngeal swabs were tested for respiratory viruses with PCR. We described the clinical characteristics of hMPV patients in comparison with those with respiratory syncytial virus (RSV) and those with neither RSV nor hMPV, and among different hMPV genotypes. Among 8822 patients, 278 (3.2%) were hMPV positive, with a median age of 21.0 months (interquartile range: 12.7-32.5). Among single virus-positive patients, hMPV cases were older than patients with RSV (p < 0.001) and without RSV (p = 0.003). The proportions of clinical pneumonia and wheezing in hMPV patients resembled those in RSV patients but were higher than in non-RSV non-hMPV patients. Seventy percent (n = 195) were genotyped (A2b: n = 40, 20.5%; A2c: n = 99, 50.8%; B1: n = 37, 19%; and B2: n = 19, 9.7%). The wheezing frequency was higher in A2b patients (76.7%) than in those with other genotypes (p = 0.033). In conclusion, we found a moderate variation in clinical features among hMPV patients with various genotypes. No seasonality was observed, and the multiple genotype co-circulation was evident.
Topics: Child; Humans; Infant; Metapneumovirus; Child, Hospitalized; Molecular Epidemiology; Respiratory Sounds; Vietnam; Respiratory Tract Infections; Respiratory Syncytial Virus, Human
PubMed: 37735242
DOI: 10.1038/s41598-023-42692-z -
PLoS Pathogens Feb 2024Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and...
Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III interferon (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity.
Topics: Child; Animals; Mice; Humans; Metapneumovirus; Interferon Lambda; Paramyxoviridae Infections; Lung; Respiratory Tract Infections; Interferons
PubMed: 38315735
DOI: 10.1371/journal.ppat.1011840 -
Transboundary and Emerging Diseases Nov 2022Given the avian metapneumovirus (aMPV) disease burden in poultry worldwide and the evidence of a possible role played by wild birds in the virus epidemiology, the... (Meta-Analysis)
Meta-Analysis
Given the avian metapneumovirus (aMPV) disease burden in poultry worldwide and the evidence of a possible role played by wild birds in the virus epidemiology, the present study summarizes aMPV serological and molecular data on free-ranging avifauna available in the literature by conducting a systematic review and meta-analysis. A computerized literature research was performed on PubMed, Scopus, CAB Direct and Web of Science to identify relevant publications across the period 1990-2021, along with the screening of reference lists. A random-effect model was applied to calculate pooled prevalence estimates with 95% confidence intervals. The inconsistency index statistic (I ) was applied to assess between-study heterogeneity. Subgroup analyses for molecular studies only were performed according to geographical area of samplings, taxonomic order, genus and migration patterns of the birds surveyed. A total of 11 publications on molecular surveys and 6 on serological ones were retained for analysis. The pooled molecular prevalence was 6% (95% CI: 1-13%) and a high between-study heterogeneity was detected (I = 96%, p < .01). Moderator analyses showed statistically significant differences according to geographical area studied, taxonomic order and genus. Concerning serological prevalence, a pooled estimate of 14% (95% CI: 1-39%), along with a high between-study heterogeneity, was obtained (I = 98%, p < .01). Moderator analysis was not performed due to the scarcity of eligible serological studies included. Overall, molecular and serological evidence suggests that some wild bird taxa could play a role in aMPV epidemiology. Particularly, wild ducks, geese, gulls and pheasants, according to scientific contributions hereby considered, proved to be susceptible to aMPV, and due to host ecology, may act as a viral carrier or reservoir. Further surveys of wild birds are encouraged for a better comprehension of the poultry/wild bird interface in aMPV epidemiology and for better characterizing the virus host breadth.
Topics: Animals; Metapneumovirus; Paramyxoviridae Infections; Animals, Wild; Ducks; Geese; Poultry Diseases; Chickens
PubMed: 35960706
DOI: 10.1111/tbed.14680