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Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in ß-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
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Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Camundongos , Humanos , Animais , Pré-Escolar , Idoso , Linfócitos T CD8-Positivos , RNA Ribossômico 16S , Camundongos Endogâmicos C57BL , Imunidade Adaptativa , Inflamação , Imunoglobulina ARESUMO
Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71+ and FasL+) CD8+ T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.
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Metapneumovirus , Infecções por Paramyxoviridae , Animais , Linfócitos T CD8-Positivos , Feminino , Humanos , Pulmão , Contagem de Linfócitos , Masculino , CamundongosRESUMO
Human metapneumovirus (hMPV) has emerged as a frequent cause of acute respiratory infections (ARI) among young children. The prevalence and genetic diversity of hMPV circulating in Chennai, Southern India, has not been studied yet. Hence, this study was aimed to investigate the prevalence, co-infection with other respiratory viruses like HRSV A and B, influenza A and B, hRV and HPIV 1-4 viruses, socio-demographic associations, and genotypes of hMPV among children in Chennai. A total of 350 nasal swab specimens were collected from children with ARI during April 2016 to August 2018 and tested for hMPV by real time PCR method. In this study, hMPV was detected in 4% (14/350) of the samples. One hMPV positive sample was found to be co-infected with influenza B virus. The mean and median ages of the children with hMPV infection were 61.5 months (5.1 years) and 83 months (6.9 years), respectively. Phylogenetic analysis of the partial F gene revealed the presence of A2c subcluster among the study strains as well as with B1 and B2 lineages. The prevalence data obtained in this study is important in evaluating the role of hMPV in childhood ARI and emphasizes the importance of routine viral diagnosis in hospitals. To the best of our knowledge, this is the first study to report the prevalence, seasonality, and genetic diversity of hMPV in Chennai as well as the first study to report A2c subcluster of hMPV among children in India.
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Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Pré-Escolar , Humanos , Índia/epidemiologia , Lactente , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , Filogenia , Infecções Respiratórias/epidemiologiaRESUMO
The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.
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Human metapneumovirus (hMPV) is an emergent virus, which mainly infects the upper and lower respiratory tract epithelium. This pathogen is responsible for a significant portion of hospitalizations due to bronchitis and pneumonia in infants and the elderly worldwide. hMPV infection induces a pro-inflammatory immune response upon infection of the host, which is not adequate for the clearance of this pathogen. The lack of knowledge regarding the different molecular mechanisms of infection of this virus has delayed the licensing of effective treatments or vaccines. As part of this work, we evaluated whether a single and low dose of a recombinant Mycobacterium bovis Bacillus Calmette-Guérin (BCG) expressing the phosphoprotein of hMPV (rBCG-P) can induce a protective immune response in mice. Immunization with the rBCG-P significantly decreased neutrophil counts and viral loads in the lungs of infected mice at different time points. This immune response was also associated with a modulated infiltration of innate cells into the lungs, such as interstitial macrophages (IM) and alveolar macrophages (AM), activated CD4+ and CD8+ T cells, and changes in the population of differentiated subsets of B cells, such as marginal zone B cells and plasma cells. The humoral immune response induced by the rBCG-P led to an early and robust IgA response and a late and constant IgG response. Finally, we determined that the transfer of cells or sera from immunized and infected mice to naïve mice promoted an efficient viral clearance. Therefore, a single and low dose of rBCG-P can protect mice from the disease caused by hMPV, and this vaccine could be a promising candidate for future clinical trials.
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Metapneumovirus , Mycobacterium bovis , Animais , Vacina BCG , Linfócitos T CD8-Positivos , Camundongos , Camundongos Endogâmicos BALB C , Vacinas SintéticasRESUMO
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.
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Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/fisiologia , Animais , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Metapneumovirus/genética , Neutrófilos/imunologia , Infecções por Paramyxoviridae/genética , Infecções por Paramyxoviridae/virologia , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genéticaRESUMO
Resumen En el 2001, se identificó en Holanda al metapneumovirus humano (hMPV) como un "nuevo" agente etiológico causante de infecciones respiratorias agudas en infantes menores de 5 años; sin embargo, también se ha aislado en personas de la tercera edad e inmunocomprometidos. Este virus se considera como el segundo agente etiológico en enfermedades agudas del tracto respiratorio. En la actualidad, el costo estimado de las infecciones respiratorias agudas (IRA) en nuestro país es de 9,000 dólares estadounidenses por paciente hospitalizado. El hMPV es un miembro del género Metapneumovirus, familia Pneumoviridae, que pertenece al orden de los Mononegavirales, correspondiente a virus de ácido ribonucleico (RNA) monocatenario negativo, que consta de 8 genes en el orden 3'-N-P-M-F-M2-SH-G-L-5', y que codifica para 9 proteínas. De estas proteínas, la glicoproteína de fusión F está altamente conservada en el género Metapneumovirus y es el mayor determinante antigénico, y al no existir aún vacuna aprobada para este virus, se ha utilizado como un epítopo candidato para el diseño de una vacuna que confiera inmunidad al hospedero o como un blanco terapéutico en la creación de péptidos antivirales que inhiban la fusión del virus a su célula blanco y se evite la infección en sujetos de alto riesgo de contagio, ya que en la actualidad no se ha aprobado por la COFEPRIS ningún tratamiento profiláctico contra hMPV.
Abstract In 2001 in the Netherlands, Human metapneumovirus (hMPV) was identified as a "new" etiologic agent causing acute respiratory infections in children younger than 5 years old; however, it has also been isolated in the elderly and immunocompromised people. This virus is considered the second etiological agent in acute diseases of the respiratory tract. Currently, the estimated cost of IRAs in our country is of 9,000 USD per inpatient. hMPV is a member of the genus Metapneumovirus, family Pneumoviridae, and it belongs to the order Mononegavirales that is part of the negative single-stranded ribonucleic acid (RNA) virus, consisting of eight genes ordered: 3'-N-P-M-F-M2-SH-G-L-5 ', and which encodes for 9 proteins. Of these proteins, the F fusion glycoprotein is highly conserved in the genus Metapneumovirus, and is the major antigenic determinant, and because an approved vaccine doesn't exist, it has been used as a candidate epitope for the design of a vaccine that confers host immunity or as a therapeutic target in the creation of antiviral peptides that inhibit the fusion of the virus to its target cell and to avoid infection in subjects at high risk of contagion since there is currently none accepted by COFEPRIS as a prophylactic treatment against hMPV.
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Cancer is the first cause of death by disease in childhood globally. The most frequent types of cancers in children and adolescents are leukemias, followed by brain and central nervous system tumors and lymphomas. The recovery rate of cancer in children is around 80% in developed countries and up to 30% in developing countries. Some of the main causes of complications in children and adolescents with cancer are respiratory viral infections, mainly in bone marrow-transplanted patients. Respiratory viruses have been detected in the bronchoalveolar lavage or nasal wash specimens from cancer patients with or without respiratory illness symptoms. Human metapneumovirus (HMPV) is within the ten most common viruses that are encountered in samples from pediatric patients with underlying oncology conditions. In most of cases, HMPV is found as the only viral agent, but co-infection with other viruses or with bacterial agents has also been reported. The discrepancies between the most prevalent viral agents may be due to the different populations studied or the range of viral agents tested. Some of the cases of infection with HMPV in cancer patients have been fatal, especially in those who have received a hematopoietic stem cell transplant. This review seeks to show a general view of the participation of HMPV in respiratory illness as a complication of cancer in childhood and adolescence.
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Human metapneumovirus is an emerging pathogen that causes upper and lower respiratory illness. Nursing home outbreaks of infection with this virus can cause severe illness and lead to poor patient outcomes. We report an outbreak investigation in a nursing home during 2018 and infection control guidelines to assist in disease control.
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Surtos de Doenças , Metapneumovirus , Casas de Saúde , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Humanos , Metapneumovirus/classificação , Metapneumovirus/genética , New Mexico/epidemiologia , Infecções por Paramyxoviridae/diagnóstico , Infecções Respiratórias/diagnóstico , Estados Unidos/epidemiologiaRESUMO
The Human Respiratory Syncytial Virus (hRSV) and the Human Metapneumovirus (hMPV) are two pneumoviruses that are leading agents causing acute lower respiratory tract infections (ALRTIs) affecting young infants, the elderly, and immunocompromised patients worldwide. Since these pathogens were first discovered, many approaches for the licensing of safe and effective vaccines have been explored being unsuccessful to date. We have previously described that immunization with recombinant strains of Mycobacterium bovis Bacillus Calmette-Guérin (rBCG) expressing the hRSV nucleoprotein (rBCG-N) or the hMPV phosphoprotein (rBCG-P) induced immune protection against each respective virus. These vaccines efficiently promoted viral clearance without significant lung damage, mainly through the induction of a T helper 1 cellular immunity. Here we show that upon viral challenge, rBCG-immunized mice developed a protective humoral immunity, characterized by production of antibodies specific for most hRSV and hMPV proteins. Further, isotype switching from IgG1 to IgG2a was observed in mice immunized with rBCG vaccines and correlated with an increased viral clearance, as compared to unimmunized animals. Finally, sera obtained from animals immunized with rBCG vaccines and infected with their respective viruses exhibited virus neutralizing capacity and protected naïve mice from viral replication and pulmonary disease. These results support the notion that the use of rBCG strains could be considered as an effective vaccination approach against other respiratory viruses with similar biology as hRSV and hMPV.
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Vacina BCG/imunologia , Imunidade Humoral , Mycobacterium bovis/imunologia , Infecções Respiratórias/prevenção & controle , Animais , Vacina BCG/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Metapneumovirus/genética , Metapneumovirus/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nucleoproteínas/administração & dosagem , Nucleoproteínas/genética , Nucleoproteínas/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Células Th1/imunologia , Células Th1/metabolismo , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Proteínas Virais/imunologia , Replicação Viral/imunologiaRESUMO
Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models.
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Human Respiratory Syncytial Virus (hRSV), human Metapneumovirus (hMPV) and Adenovirus (ADV), are three of the most prevalent viruses responsible for pneumonia and bronchiolitis in children and elderly worldwide, accounting for a high number of hospitalizations annually. Diagnosis of these viruses is required to take clinical actions that allow an appropriate patient management. Thereby, new strategies to design fast diagnostic methods are highly required. In the present work, six monoclonal antibodies (mAbs, two for each virus) specific for conserved proteins from hRSV, hMPV and ADV were generated and evaluated through different immunological techniques, based on detection of purified protein, viral particles and human samples. In vitro evaluation of these antibodies showed higher specificity and sensitivity than commercial antibodies tested in this study. These antibodies were used to design a sandwich ELISA tests that allowed the detection of hRSV, hMPV, and ADV in human nasopharyngeal swabs. We observed that hRSV and ADV were detected with sensitivity and specificity equivalent to a current Direct Fluorescence Assay (DFA) methodology. However, hMPV was detected with more sensitivity than DFA. Our data suggest that these new mAbs can efficiently identify infected samples and discriminate from patients infected with other respiratory pathogens.
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Adenovírus Humanos/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Metapneumovirus/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Proteínas Virais/imunologia , Adenovírus Humanos/genética , Animais , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Metapneumovirus/genética , Camundongos , Vírus Sincicial Respiratório Humano/genética , Sensibilidade e EspecificidadeRESUMO
The human metapneumovirus (hMPV) is the second leading cause globally of acute infection of the respiratory tract in children, infecting the upper and lower airways. The hMPV may induce an inappropriate Th2-type immune response, which causes severe pulmonary inflammation, leading to the obstruction of airways. Despite its severe epidemiological relevance, no vaccines are currently available for the prevention of hMPV-induced illness. In this investigation, we demonstrated that immunization of mice with the recombinant hMPV nucleoprotein (hMPV-N) mixed with the AbISCO-100 adjuvant reduced viral replication in lungs following challenge with the virus. We found that immunized mice had reduced weight loss, decreased granulocytes in the lung, an increased level of specific nucleoprotein antibodies of IgG1 and IgG2a-isotypes, and a local profile of Th1/Th17-type cytokines. Our results suggest that immunization with the hMPV-N and the AbISCO-100 adjuvant induces a reduction of viral infection and could be considered for the development of an hMPV vaccine.
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Imunização , Metapneumovirus/imunologia , Nucleoproteínas/administração & dosagem , Infecções por Paramyxoviridae/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/classificação , Citocinas/análise , Células Dendríticas/classificação , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Granulócitos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Nucleoproteínas/genética , Nucleoproteínas/isolamento & purificação , Infecções por Paramyxoviridae/prevenção & controle , Pneumonia/virologia , RNA Viral/análise , Vacinas Virais/farmacologia , Redução de PesoRESUMO
INTRODUCTION: Human metapneumovirus (hMPV) has become one of the major pathogens causing acute respiratory infections (ARI) mainly affecting young children, immunocompromised patients, and the elderly. Currently there are no licensed vaccines against this virus. Areas covered: Since the discovery of hMPV in 2001, many groups have focused on developing vaccines against this pathogen. This review presents the outcomes and perspectives derived from preclinical studies performed in cell cultures and animals as well as the only candidate that has reached evaluation in a clinical trial. Limitations of the current vaccine candidates are discussed and perspectives for the development of plant-based vaccines are analyzed. Expert commentary: Several hMPV vaccine candidates are under development with the potential to progress into clinical trials. In parallel, the molecular farming field offers new opportunities to generate innovative vaccines that will offer several advantages in the fight against hMPV.
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Metapneumovirus/imunologia , Infecções por Paramyxoviridae/prevenção & controle , Vacinas Virais/imunologia , Vacinas Virais/isolamento & purificação , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Descoberta de Drogas/tendências , Avaliação Pré-Clínica de Medicamentos , Humanos , Modelos Biológicos , Infecções por Paramyxoviridae/imunologiaRESUMO
Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections. In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.
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Metapneumovirus/patogenicidade , Infecções por Paramyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa , Idoso , Animais , Linfócitos B/imunologia , Criança , Citocinas , Humanos , Evasão da Resposta Imune , Lactente , Metapneumovirus/imunologia , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/virologia , Pneumonia/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/fisiologia , Infecções Respiratórias/virologia , Replicação ViralRESUMO
Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.
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Citocinas/metabolismo , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/metabolismo , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Transdução de Sinais , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Linhagem Celular , Citocinas/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Expressão Gênica , Humanos , Interleucina-33 , Interleucina-8/genética , Interleucina-8/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Metapneumovirus/efeitos dos fármacos , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Ligante OX40/antagonistas & inibidores , Ligante OX40/genética , Ligante OX40/metabolismo , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/genética , Infecções por Paramyxoviridae/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Pneumonia Viral/patologia , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/deficiência , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Replicação Viral , Linfopoietina do Estroma do TimoRESUMO
El Metapneumovirus humano (hMPV) constituye una importante causa de Infecciones Respiratorias Agudas (IRAs) en niños hospitalizados. En Paraguay, las IRAs están entre las primeras causas de hospitalización durante la infancia, siendo los virus los principales agentes causales. Sin embargo, aún persiste una alta proporción de casos sin etiología identificada. La pandemia de Influenza en el año 2009, condujo a una intensificación de la vigilancia de las infecciones respiratorias, lo cual permitió al mismo tiempo la búsqueda de otros virus como el hMPV. Nuestro objetivo fue detectar hMPV en niños hospitalizados por IRAs en Paraguay durante el año 2009. Fueron estudiadas 240 muestras respiratorias de niños < 5 años internados por IRAs en Paraguay durante el año 2009, que habían resultado negativas para otros virus respiratorios. Fue utilizado el reactivo LightMix Kit human MPV de TIBMOLBIOL, para la detección del gen N de hMPV por PCR en Tiempo Real, siguiendo el procedimiento indicado por el fabricante. De las 240 muestras estudiadas, 29 (12%) resultaron positivas para hMPV, con la mayor detección en julio y agosto; predominando en mayores de 1 año. Los principales signos y síntomas fueron tos, fiebre y dificultad respiratoria; y las complicaciones más frecuentes neumonía y bronquiolitis. Estos resultados proveen las primeras evidencias en Salud Pública, de la importancia del hMPV asociado a niños hospitalizados por IRAs en Paraguay.
Human metapneumovirus (hMPV) is a significant cause of acute respiratory infection (ARI) in hospitalized children. In Paraguay, ARI is one of the leading causes of childhood hospitalization, with viruses being the primary causal agents. However, a large number of cases of unknown etiology remain. The influenza pandemic of 2009 led to intensified vigilance concerning respiratory infections and more thorough efforts to confirm the presence of viruses such as hMPV. Our objective was to detect hMPV in children hospitalized for ARI in Paraguay during 2009. We studied respiratory samples from 240 children age < 5 years hospitalized for IRAs in Paraguay during 2009 who had tested negative for other respiratory viruses. We used the hMPV-reactive LightMix® kit from TIB MOLBIOL for the detection of the nucleoprotein (N) gene by real-time PCR according to manufacturer-specified procedures. Of the 240 samples studied, 29 (12%) were positive for hMPV, with the highest rates detected in July and August (winter) predominating in children over 1 year of age. The most common signs and symptoms were cough, fever, and respiratory distress; while the most common complications were pneumonia and bronchiolitis. These results provide the first evidence concerning the prevalence of hMPV in children hospitalized for ARI in Paraguay.
RESUMO
O Vírus respiratório sincicial humano (hRSV - human respiratory syncytial virus) e o Metapneumovírus humano (hMPV - human metapneumovirus) são os principais agentes etiológicos identificados nas infecções respiratórias agudas (IRAs). As IRAs representam importante causa de morbidade e mortalidade em crianças no mundo todo. hRSV e hMPV são membros da família Paramyxoviridae. São vírus envelopados, não-segmentados dotados de genoma de RNA de fita simples com sentido negativo. O hRSV é o agente viral melhor caracterizado neste grupo, associado à doença do trato respiratório inferior. Recentemente foi identificado um novo patógeno humano pertencente à subfamília Pneumovirinae, o hMPV, o qual possui similaridades com o hRSV, na sua organização genômica, estrutura viral, antigenicidade e sintomas clínicos. A subfamília Pneumovirinae contém dois gêneros: gênero Pneumovirus que contêm o hRSV, o RSV bovino (bRSV - bovine RSV), bem como os RSV ovino, caprino e o vírus da pneumonia murina, o segundo gênero Metapneumovirus que consiste do MPV aviário (aMPV - avian MPV) e hMPV. Neste trabalho, apresentamos uma breve revisão narrativa da literatura sobre aspectos importantes da biologia, epidemiologia e manifestações clínicas das infecções por estes dois vírus respiratórios.
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are the main etiological agents of acute respiratory infections (ARIs). ARIs are an important cause of childhood morbidity and mortality worldwide. The hRSV and hMPV are members of the Paramyxoviridae family. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. The respiratory syncytial virus (hRSV) is the best characterized viral agent of this group, associated with respiratory diseases in the lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV), which is structurally similar to the hRSV in terms of genomic organization, viral structure, antigenicity, and clinical symptoms. The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains the hRSV, the bovine RSV (bRSV), as well as the ovine and caprine RSV and pneumonia virus of mice, the second genus Metapneumovirus, consists of the avian MPV (aMPV) and hMPV. In this study, we present a brief review of the literature on important aspects of the biology, epidemiology, and clinical manifestations of infections by two respiratory viruses.
Assuntos
Humanos , Masculino , Feminino , Metapneumovirus/patogenicidade , Infecções por Vírus Respiratório Sincicial , Viroses , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/patologia , Infecções Respiratórias/terapia , Infecções Respiratórias/transmissãoRESUMO
Metapneumovirus humano (MPVh), agente de infección respiratoria aguda baja (IRAB) recientemente descrito, ha sido detectado en 5,4 por ciento de lactantes chilenos hospitalizados por IRAB, con estudio negativo para virus respiratorio sincicial, adenovirus, parain-fluenza e influenza. Puede determinar bronquiolitis o neumonía en hospitalizados, en ocasiones llega a requerir conexión a ventilación mecánica y tratamiento en una unidad de cuidados intensivos. En algunos casos se presenta como apnea, situación que es más frecuente en prematuros. Está descrita su transmisión nosocomial. Presentamos el caso de un lactante de un mes de edad, con apnea, antecedente de prematurez e infección por MPVh y una probable adquisición intrahospitalaria. Se revisan las características clínicas de la infección por este agente y se discute la asociación con apnea e infección nosocomial. El MPVh debiera ser incluido en el estudio etiológico de lactantes que presentan apnea con estudio viral convencional negativo y como agente respiratorio de infección nosocomial
Human metapneumovirus (hMPV), a recently described pathogen of lower respiratory tract infections (LRTI), has been detected in 5,4 percent of Chilean infants hospitalized for LRTI whom are negative for adenovirus, respiratory syncytial virus, influenza and parainfluenza viruses. hMPV may cause bronchiolitis or pneumonia in hospitalized patients, and ocassionally require admission to intensive care units and mechanical ventilation. The infection has been associated with apnea, especially in preterm infants. Nosocomial dissemination has also been described. We present the case of a one-month-of age premature infant with apnea, and infection caused by hMPV of probable nosocomial aquisition. Clinical features of hMPV infection are reviewed and its association with apnea and nosocomial transmission is discussed. hMPV should be included in the routine diagnosis of respiratory viruses in infants with apnea and should be considered among the respiratory pathogens associated with nosocomial transmission