scholarly journals Human Metapneumovirus Induces Mucin 19 Which Contributes to Viral Pathogenesis

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 726
Author(s):  
Kaitlin McBride ◽  
Ma. del Rocio Banos-Lara ◽  
Nagarjuna R. Cheemarla ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Human Metapneumovirus ◽  
Hmpv Infection ◽  
Lower Lung ◽  
Tract Infections ◽  
Mouse Model Of Infection

Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.

scholarly journals Metapneumovirus infection in children

2020 ◽  
Vol 11 (5) ◽  
pp. 13-19
Author(s):  
Elena V. Sharipova ◽  
Irina V. Babachenko ◽  
Elizaveta D. Orlova
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Hospitalized Children ◽  
Lower Respiratory Tract Infections ◽  
Nucleic Acid Isolation ◽  
Hmpv Infection ◽  
Tract Infections

Objective: to study the clinical features of metapneumovirus infection in children of different ages in a hospital. Materials and methods. A retrospective analysis of medical records of 142 patients aged 1 month to 14 years inclusive who were hospitalized in the period from January 2012 to April 2019. Metapneumovirus infection was confirmed by hMPV nucleic acid isolation by PCR in nasopharyngeal smears. Results. Metapneumovirus infection is detected among hospitalized children with acute respiratory viral infections in 4,4% of cases. In the age structure, 72,2% are children under 4 years old, and the maximum incidence rate is among children aged 3 years of life. The leading clinical symptoms are cough in 93,0% of cases and rhinitis in 96,5% of cases.In 88,2% of children, the disease proceeds with an increase in temperature 38 C, including in 34,6% 39,5 C and above. Symptoms of gastrointestinal dysfunction in the form of vomiting and diarrhea develop in 26,1% and 22,5% of children, respectively. 78,2% of patients requiring hospitalization suffer hMPV infection with damage to the lower respiratory tract, including in the form of bronchitis in 85,6% of cases and pneumonia in 14,4% of cases. The disease is complicated by the development of bronchial obstructive syndrome in 38,7% and acute respiratory failure in 22,3% of cases. ARF and BOS are significantly more likely to develop in children of the first 3 years of life 71,0% versus 29,0% in children of the older age group (p = 0.038) and 69,8% against 30,2% (p = 0.007), respectively. In a clinical blood test for hMPV infection, leukopenia and leukocytosis are detected only in 3,5% and 12,7% of cases, respectively, as well as an increase in ESR in 23,9% of children. The level of CRP in the 93,0% of children was less than 20 mg/l. Conclusions. Virological confirmation of metapneumovirus infection in hospitalized children with lower respiratory tract infections contributes to the formation of an adequate therapeutic tactic.

scholarly journals Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection

2014 ◽  
Vol 89 (1) ◽  
pp. 730-742 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Lindsey Harvey ◽  
Alexander Mendoza ◽  
Dawn Simms ◽  
Vladimir N. Chouljenko ◽  
...  
Keyword(s):  
Immune Response ◽  
Protective Role ◽  
Human Metapneumovirus ◽  
Interferon Response ◽  
Antiviral Immune Response ◽  
Hmpv Infection ◽  
Experimental Mouse ◽  
Mouse Model Of Infection

ABSTRACTHuman metapneumovirus (hMPV) is a respiratory paramyxovirus that is distributed worldwide and induces significant airway morbidity. Despite the relevance of hMPV as a pathogen, many aspects of the immune response to this virus are still largely unknown. In this report, we focus on the antiviral immune response, which is critical for viral clearance and disease resolution. Usingin vitroandin vivosystems, we show that hMPV is able to induce expression of lambda interferon 1 (IFN-λ1), IFN-λ2, IFN-λ3, and IFN-λ4. The induction of IFN-λ expression by hMPV was dependent on interferon regulatory factor 7 (IRF-7) expression but not on IRF-3 expression. Treatment of hMPV-infected mice with IFN-λ reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN-λ response induced by the virus was regulated by the expression of the hMPV G protein. These results show that type III interferons (IFN-λs) play a critical protective role in hMPV infection.IMPORTANCEHuman metapneumovirus (hMPV) is a pathogen of worldwide importance. Despite the relevance of hMPV as a pathogen, critical aspects of the immune response induced by this virus remain unidentified. Interferons (IFNs), including IFN-λ, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN-λ exhibited a protective role in hMPV infectionin vitroand in an experimental mouse model of infection.

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

scholarly journals Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response

2020 ◽  
Vol 8 (6) ◽  
pp. 824
Author(s):  
Antonella Bugatti ◽  
Stefania Marsico ◽  
Manuela Fogli ◽  
Sara Roversi ◽  
Serena Messali ◽  
...  
Keyword(s):  
Immune Response ◽  
Endothelial Cells ◽  
Human Metapneumovirus ◽  
Size Exclusion ◽  
Microvascular Endothelial Cells ◽  
Cytopathic Effects ◽  
Viral Particles ◽  
Hmpv Infection ◽  
Microvascular Endothelial ◽  
Tract Infections

Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.

scholarly journals Molecular Diagnosis of Human Metapneumovirus in Hospitalized Children with Acute Respiratory Tract Infections using RT-LAMP: A Population-Based Prospective Study

2021 ◽  
Vol 11 (2) ◽  
pp. 146-150
Author(s):  
Ahmed Osman Gasim Attar ◽  
Khalid Enan ◽  
Sara Abdelghani ◽  
Lienda Bashier Eltayeb
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Clinical Symptoms ◽  
Diagnostic Technique ◽  
Lamp Assay ◽  
Human Metapneumovirus ◽  
Hospitalized Children ◽  
Age Group ◽  
Acute Respiratory Tract Infections ◽  
Tract Infections

Background: Human metapneumovirus (hMPV) is a major novel cause of acute respiratory infections ranging from wheezing to bronchiolitis and pneumonia in children worldwide. The aim of this study was to detect hMPV in hospitalized children with acute respiratory tract infections (ARTIs) by using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay. Methods and Results: A total of 68 children with ARTIs who were clinically suspected of acquiring hMPV were included in the study in the period between January 2019 and February 2020. Posterior-pharyngeal (throat) swabs were obtained from each patient. hMPV RNA was revealed in 18(26.5%) cases. The age range was from <1 year to 10 years (mean age of 5.25±2.62). Sixteen (23.5%) of the participants were in the age group of <1 year, where the majority of hMPV-positive subjects (n=11) were found (16.2% of the total number of infected children) (P=0.0025). The majority of hMPV-negative subjects (n=15) were found in the age group of 5-10 years (22% of the total number of infected children) (P=0.0025). Cough, fever, and shortness of breath were common symptoms in hMPV-positive children: 15(83.3%), 13(72.2%), and 12(66.7%), respectively. There was a statistically significant correlation between common clinical symptoms and the age group of hMPV-positive children: symptoms were common in the age group of <1 year. Conclusion: Our study represents the first report in Khartoum, Sudan, on the detection of hMPV using RT-LAMP. RT-LAMP is a valuable, quick diagnostic technique for hMPV detection.

scholarly journals Human Metapneumovirus Impairs Apoptosis of Nasal Epithelial Cells in Asthma via HSP70

2016 ◽  
Vol 9 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Engin Baturcam ◽  
Natale Snape ◽  
Tiong Han Yeo ◽  
Johanna Schagen ◽  
Emma Thomas ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Infections ◽  
Airway Epithelial Cells ◽  
Human Metapneumovirus ◽  
Airway Epithelial ◽  
Caspase Activation ◽  
Nasal Epithelial Cells ◽  
Hmpv Infection ◽  
Syncytial Virus

Asthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response. NECs from these asthmatics supported elevated hMPV but not RSV infection, compared to non-asthmatic controls. This correlated with reduced apoptosis and reduced activation of caspase-9 and caspase-3/7 in response to hMPV, but not RSV. The expression of heat shock protein 70 (HSP70), a known inhibitor of caspase activation and subsequent apoptosis, was amplified in response to hMPV infection. Chemical inhibition of HSP70 function restored caspase activation and reduced hMPV infection in NECs from asthmatic subjects. There was no impairment in the production of IFN by NECs from asthmatics in response to either hMPV or RSV, demonstrating that increased infection of asthmatic airway cells by hMPV is IFN-independent. This study demonstrates, for the first time, a mechanism for elevated hMPV infection in airway epithelial cells from adult asthmatics and identifies HSP70 as a potential target for antiviral and asthma therapies.

scholarly journals Identification and Evaluation of a Highly Effective Fusion Inhibitor for Human Metapneumovirus

2007 ◽  
Vol 52 (1) ◽  
pp. 279-287 ◽  
Author(s):  
Céline Deffrasnes ◽  
Marie-Ève Hamelin ◽  
Gregory A. Prince ◽  
Guy Boivin
Keyword(s):  
Fusion Protein ◽  
Clinical Symptoms ◽  
Pulmonary Inflammation ◽  
Human Metapneumovirus ◽  
Heptad Repeat ◽  
Elderly Subjects ◽  
Monocyte Chemoattractant Protein 1 ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACT Human metapneumovirus (hMPV) can cause acute upper and lower respiratory tract infections that are particularly severe in young children, elderly subjects, and immunocompromised patients. To date, no treatments or vaccines are available for hMPV infections. Our objective was to assess the inhibitory potential of several peptides derived from the heptad repeat A and B (HRA and HRB) domains of the hMPV fusion protein. Nine candidate peptides were expressed in Escherichia coli or obtained synthetically and tested in vitro and in an animal model. Excellent in vitro inhibition of an hMPV strain of the A1 subgroup was obtained with five peptides, with 50% inhibitory concentrations ranging from 1.4 nM to 3.3 μM. One peptide, HRA2, displayed very potent activity against all four hMPV subgroups. It was also moderately active against human respiratory syncytial virus (strain A2) but displayed no activity against human parainfluenza virus type 3. BALB/c mice that received the HRA2 peptide and a lethal hMPV intranasal challenge simultaneously were completely protected from clinical symptoms and mortality. On day 5 postinfection, HRA2-treated mice had undetectable lung viral loads which were significantly less than those of untreated mice (3 × 104 50% tissue culture infective doses/lung). Pulmonary inflammation, levels of proinflammatory cytokines/chemokines (RANTES, gamma interferon, and monocyte chemoattractant protein 1) and airway obstruction were also significantly decreased in HRA2-treated mice. The results of this study demonstrate that potent antivirals can be derived from the hMPV fusion protein HR domains. Moreover, hMPV, compared to other paramyxoviruses and to the human immunodeficiency virus, seems to be more susceptible to HRA- than HRB-derived peptides.

Human Metapneumovirus Infection In Children with Cancer

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3910-3910
Author(s):  
Muhammad Ali ◽  
Jillian Baker ◽  
Susan Elaine Richardson ◽  
Upton Allen ◽  
Oussama Abla
Keyword(s):  
Respiratory Tract ◽  
Average Duration ◽  
Respiratory Illness ◽  
Human Metapneumovirus ◽  
Upper Respiratory Tract ◽  
Children With Cancer ◽  
Hmpv Infection ◽  
Respiratory Tract Illness ◽  
Upper Respiratory ◽  
Tract Infections

Abstract Abstract 3910 The human metapneumovirus (HMPV) is a paramyxovirus that has been recently associated with respiratory tract infections in children. HMPV was first described in 2001 by researchers in the Netherlands. Since this initial report, HMPV has been reported from many other countries across the world. HMPV was found to be the second most frequent cause, after RSV, of viral respiratory infections in children less than 1 year of age. In hospitalized children, the most frequent clinical manifestations associated with HMPV are pneumonitis, bronchiolitis and asthma. Severe HMPV infection can also occur in the elderly and in immunocompromised patients. We carried out a retrospective study to describe the clinical features and severity of HMPV in pediatric oncology patients at The Hospital for Sick Children. Thirty one children with cancer found to have HMPV infection during the study period from January 2005 till December 2010. HMPV was isolated by nasopharyngeal (NP) swab in 30/31 patients while one patient had bronchalveolar lavage (BAL). Direct fluorescent-antibody (DFA) was positive in all 31 patients while 13 patients also had viral culture positive. Eight patients had culture negative while this test was not done in 10 patients (after December 2008). The majority of HMPV infection was diagnosed in the winter months from November to March and also in the spring till May. Of 31 patients, 13 were male and 18 were female. The most common underlying diagnosis was leukemia 14/31 (45.1%). Nine patients had different types of solid tumours including 3 with neuroblastoma, 2 with rhabdomyosarcoma, 1 with hepatoblastoma, 1 with nasopharyngeal sarcoma, and 1 with undifferentiated sarcoma. Twenty-nine of thirty-one (93.5%) of the patients presented with cough, 24/31 (77.4%) with fever, 16/31 (51.6%) with rhinorrhea. Vomiting was noticed in 25.8% of the patients and diarrhea in 32.2%. Sixteen of thirty-one (51.6%) patients were diagnosed with upper respiratory tract infection (URTI), 7/31 (22.5%) patients were diagnosed as bronchiolitis and 8/31 (25.8%) diagnosed to have pneumonia. 19.3% (6/31) patients had co-infection with different organisms including coagulase negative Staphylococcus and Streptococcus pneumoniae requiring antibiotic treatment. The average duration of symptoms on presentation was 7 days (1-90 days). One patient with average risk acute lymphoblastic leukemia on maintenance treatment presented with 3 months history of cough and subsequently NP swab and BAL were positive for HMPV. He required prolonged therapy with inhaled bronchodilator and steroid. Twenty of thirty-one (64.5%) patients were admitted. The average duration of admission was 18.3 days and average duration of respiratory illness was 13.5 days. None of the patient required mechanical ventilation because of HMPV infection. Twenty-one of thirty-one patients were treated with antibiotics for duration of 3 to 14 days. One patient was empirically treated with oseltamivir (Tamiflu). All of the patients recovered from their viral illness completely, only one patient had prolonged respiratory symptoms for six months. Conclusion: Our study showed HMPV is an important respiratory virus causing both upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI) in children with cancer. Although the majority of the children recovered from HMPV infection without clinically significant illness, a minority had prolonged respiratory illness requiring supportive treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Computational studies of drugs for possible action against Covid-19 infections

2020 ◽  
Vol 10 (6) ◽  
pp. 99-105
Author(s):  
Ganesh Prasad Mishra ◽  
Debadash Panigrahi
Keyword(s):  
Respiratory Tract ◽  
Viral Infections ◽  
Drug Repositioning ◽  
In Vivo Studies ◽  
Economic Losses ◽  
Computational Docking ◽  
Molegro Virtual Docker ◽  
Tract Infections

SARS-Cov-2 has emerged highly contagious viral infections so far and posed a global threat with significant human casualties and severe economic losses. There is urgent demand to develop rational therapies to control the drastic spread of the virus. Although there is no specific regimens are available to combat this pandemic situation so far. An attempt was made to perform Insilco studies of drugs applicable to respiratory tract infections with crucial SARS-COV-2 main protease (M-pro) enzyme. Insilco docking study was performed with Molegro Virtual Docker 5.5    on number of available medications of different categories specified for respiratory tract infections.Result indicates that Azithromycin, Dexamethasone and Remdesivir are highly effective and mainly interacted with key amino acid residues with hydrogen bonds and displayed excellent docking score -133, -141 and -153 kcal/mole respectively. This study advocates the possible use Azithromycin, Dexamethasone and Remdesivir drugs in combination to battle this pandemic condition. Further, this study will provide rationalized drugs and target for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections. Keywords: Viruses, SARS-COV-2, Covid-19, Drugs, Computational docking Studies, Drug Design

Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Mononuclear Cells ◽  
Multiple Organ ◽  
Peripheral Blood Mononuclear ◽  
Dornase Alfa ◽  
Tract Infections ◽  
Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

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