Role of human metapneumovirus and respiratory syncytial virus in asthma exacerbations: where are we now?

Since its discovery in 2001, human metapneumovirus (hMPV) has been identified as an important cause of respiratory tract infection in young children, second only to the closely related respiratory syncytial virus (RSV). Clinical evidence suggests that hMPV is associated with acute exacerbations of asthma in both children and adults, and may play a role in initiating asthma development in children. Animal models have demonstrated that airway hyperresponsiveness (AHR) and inflammation are triggered following hMPV infection, and hMPV is able to persist in vivo by inhibiting innate immune responses and causing aberrant adaptive responses. In this review, we discuss the prevalence of hMPV infection in pediatric and adult populations and its potential role in asthma exacerbation. We also review recent advances made in animal models to determine immune responses following hMPV infection, and compare to what is known about RSV.

[1]  Penny A. Rudd,et al.  Human Metapneumovirus Infection in Chronic Obstructive Pulmonary Disease: Impact of Glucocorticosteroids and Interferon , 2017, The Journal of infectious diseases.

[2]  S. Liao,et al.  Defective innate immune responses to respiratory syncytial virus infection in ovalbumin-sensitized mice. , 2017, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[3]  B. Graham,et al.  Determinants of early life immune responses to RSV infection. , 2016, Current opinion in virology.

[4]  P. Jorens,et al.  The role of Th17 and Treg responses in the pathogenesis of RSV infection , 2015, Pediatric Research.

[5]  S. Varga,et al.  The Relationship Between Respiratory Syncytial Virus and Asthma , 2015, Veterinary pathology.

[6]  J. Devincenzo,et al.  Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis , 2014, The Journal of pathology.

[7]  A. Magnan,et al.  IL-17 in severe asthma. Where do we stand? , 2014, American journal of respiratory and critical care medicine.

[8]  V. Chouljenko,et al.  Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection , 2014, Journal of Virology.

[9]  Jianrong Li,et al.  Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse , 2014, Pathogens.

[10]  P. Mallia,et al.  The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease—A systematic review , 2014, Journal of Clinical Virology.

[11]  Penny A. Rudd,et al.  IRF-3, IRF-7, and IPS-1 promote host defense against acute human metapneumovirus infection in neonatal mice. , 2014, The American journal of pathology.

[12]  P. Sly,et al.  Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy , 2014, Thorax.

[13]  M. Boes,et al.  Elevated Th17 response in infants undergoing respiratory viral infection. , 2014, The American journal of pathology.

[14]  Yuwei Zhu,et al.  Respiratory syncytial virus- and human metapneumovirus-associated emergency department and hospital burden in adults , 2014, Influenza and other respiratory viruses.

[15]  D. Kim,et al.  Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations , 2014, Korean journal of pediatrics.

[16]  L. Bont,et al.  Local IL-17A Potentiates Early Neutrophil Recruitment to the Respiratory Tract during Severe RSV Infection , 2013, PloS one.

[17]  T. Warner,et al.  Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis , 2013, Infection and Immunity.

[18]  H. Kimura,et al.  Molecular epidemiology of respiratory viruses in virus-induced asthma , 2013, Front. Microbiol..

[19]  Kuender D Yang,et al.  Increased IL‐17A secreting CD4+ T cells, serum IL‐17 levels and exhaled nitric oxide are correlated with childhood asthma severity , 2013, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[20]  M. Gershwin,et al.  Respiratory Syncytial Virus—A Comprehensive Review , 2013, Clinical Reviews in Allergy & Immunology.

[21]  Y. Modis,et al.  Structural basis of innate immune recognition of viral RNA , 2013, Cellular microbiology.

[22]  P. Szilagyi,et al.  Burden of human metapneumovirus infection in young children. , 2013, The New England journal of medicine.

[23]  A. Guerrero-Plata,et al.  Critical Role of MDA5 in the Interferon Response Induced by Human Metapneumovirus Infection in Dendritic Cells and In Vivo , 2012, Journal of Virology.

[24]  K. Edwards,et al.  Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. , 2012, The Journal of infectious diseases.

[25]  Jie Zheng,et al.  Determinants of asthma after severe respiratory syncytial virus bronchiolitis. , 2012, The Journal of allergy and clinical immunology.

[26]  Y. Bi,et al.  Direct and Indirect Regulatory Mechanisms in TH17 cell Differentiation and Functions , 2012, Scandinavian journal of immunology.

[27]  J. Sprent,et al.  Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection , 2012, Mucosal Immunology.

[28]  Pingsheng Wu,et al.  Evidence for a causal relationship between respiratory syncytial virus infection and asthma , 2011, Expert review of anti-infective therapy.

[29]  E. Gelfand,et al.  The Role of RSV Infection in Asthma Initiation and Progression: Findings in a Mouse Model , 2011, Pulmonary medicine.

[30]  T. Shanley,et al.  IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. , 2011, The American journal of pathology.

[31]  R. Peebles,et al.  Viruses and asthma , 2011, Biochimica et Biophysica Acta (BBA) - General Subjects.

[32]  A. Kimura,et al.  IL‐6: Regulator of Treg/Th17 balance , 2010, European journal of immunology.

[33]  F. Finkelman,et al.  Importance of Cytokines in Murine Allergic Airway Disease and Human Asthma , 2010, The Journal of Immunology.

[34]  K. Dyer,et al.  Respiratory viruses and eosinophils: Exploring the connections , 2009, Antiviral Research.

[35]  R. Tripp,et al.  Human Metapneumovirus Establishes Persistent Infection in the Lungs of Mice and Is Reactivated by Glucocorticoid Treatment , 2009, Journal of Virology.

[36]  B. Graham,et al.  Regulatory T Cells Promote Early Influx of CD8+ T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities , 2009, Journal of Virology.

[37]  J. Gern Viral Respiratory Infection and the Link to Asthma , 2008, The Pediatric infectious disease journal.

[38]  L. Kaiser,et al.  Rhinovirus infections in infants: is respiratory syncytial virus ready for the challenge? , 2008, European Respiratory Journal.

[39]  Jianfei Yang,et al.  Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells , 2008, European journal of immunology.

[40]  R. Garofalo,et al.  T Lymphocytes Contribute to Antiviral Immunity and Pathogenesis in Experimental Human Metapneumovirus Infection , 2008, Journal of Virology.

[41]  Chen Dong,et al.  TH17 cells in development: an updated view of their molecular identity and genetic programming , 2008, Nature Reviews Immunology.

[42]  S. Phipps,et al.  Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. , 2007, Blood.

[43]  I. Casas,et al.  Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5 , 2007, Pediatric pulmonology.

[44]  S. Johnston,et al.  Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma , 2007, Journal of Allergy and Clinical Immunology.

[45]  Paul E Moore,et al.  Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. , 2007, American journal of respiratory and critical care medicine.

[46]  P. Hellings,et al.  IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? , 2006, Respiratory research.

[47]  I. Casas,et al.  Prevalence and clinical characteristics of human metapneumovirus infections in hospitalized infants in Spain , 2006, Pediatric pulmonology.

[48]  G. Boivin,et al.  Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice. , 2006, The Journal of infectious diseases.

[49]  I. Mackay,et al.  Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice , 2006, Journal of Virology.

[50]  J. Kahn,et al.  Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease , 2006, Journal of Infection.

[51]  I. Casas,et al.  Human metapneumovirus infections in hospitalised infants in Spain , 2006, Archives of Disease in Childhood.

[52]  G. Rohde,et al.  Relevance of human metapneumovirus in exacerbations of COPD , 2005, Respiratory research.

[53]  J. Crowe,et al.  Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults. , 2005, The Journal of infectious diseases.

[54]  T. Petrella,et al.  Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice. , 2005, Vaccine.

[55]  R. Tripp,et al.  The Immune Response to Human Metapneumovirus Is Associated with Aberrant Immunity and Impaired Virus Clearance in BALB/c Mice , 2005, Journal of Virology.

[56]  J. Crowe,et al.  Human metapneumovirus infection in children hospitalized for wheezing , 2005, Journal of Allergy and Clinical Immunology.

[57]  W. Shieh,et al.  Human Metapneumovirus Persists in BALB/c Mice despite the Presence of Neutralizing Antibodies , 2004, Journal of Virology.

[58]  V. Baum Human Metapneumovirus and Lower Respiratory Tract Disease in Otherwise Healthy Infants and Children , 2004 .

[59]  M. St. Claire,et al.  The Two Major Human Metapneumovirus Genetic Lineages Are Highly Related Antigenically, and the Fusion (F) Protein Is a Major Contributor to This Antigenic Relatedness , 2004, Journal of Virology.

[60]  G. Cilla,et al.  Human Metapneumovirus and Chronic Obstructive Pulmonary Disease , 2004, Emerging infectious diseases.

[61]  J. Kimpen,et al.  Human metapneumovirus infection in hospital referred South African children , 2004, Journal of medical virology.

[62]  A. Osterhaus,et al.  Identification of small-animal and primate models for evaluation of vaccine candidates for human metapneumovirus (hMPV) and implications for hMPV vaccine design. , 2004, The Journal of general virology.

[63]  S. J. Hoffman,et al.  Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy. , 2004, The Journal of infectious diseases.

[64]  O. Ruuskanen,et al.  Respiratory Picornaviruses and Respiratory Syncytial Virus as Causative Agents of Acute Expiratory Wheezing in Children , 2004, Emerging infectious diseases.

[65]  J. Kahn,et al.  A 1-Year Experience with Human Metapneumovirus in Children Aged <5 Years , 2004, The Journal of infectious diseases.

[66]  K. Edwards,et al.  Human Metapneumovirus Infection among Children Hospitalized with Acute Respiratory Illness , 2004, Emerging infectious diseases.

[67]  M. Bergeron,et al.  Human Metapneumovirus Infections in Hospitalized Children , 2003, Emerging infectious diseases.

[68]  J. Morton,et al.  Asthma exacerbations in children associated with rhinovirus but not human metapneumovirus infection. , 2003, The Journal of infectious diseases.

[69]  F. Freymuth,et al.  Presence of the new human metapneumovirus in French children with bronchiolitis , 2003, The Pediatric infectious disease journal.

[70]  O. Ruuskanen,et al.  Metapneumovirus and acute wheezing in children , 2002, The Lancet.

[71]  L. Anderson,et al.  Characterization of Human Metapneumoviruses Isolated from Patients in North America , 2002, The Journal of infectious diseases.

[72]  S. Withers,et al.  Evidence of human metapneumovirus in Australian children , 2002, The Medical journal of Australia.

[73]  T. Seemungal,et al.  Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[74]  C. Hogaboam,et al.  Respiratory Syncytial Virus Predisposes Mice to Augmented Allergic Airway Responses Via IL-13-Mediated Mechanisms1 , 2001, The Journal of Immunology.

[75]  Douglas T. Golenbock,et al.  Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus , 2000, Nature Immunology.

[76]  B. Kjellman,et al.  Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. , 2000, American journal of respiratory and critical care medicine.

[77]  D D Donaldson,et al.  Interleukin-13: central mediator of allergic asthma , 1998 .

[78]  B. Björkstén,et al.  Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. , 1995, Pediatrics.

[79]  Ph.D Monique C. de Waard,et al.  Obstructive Sleep Apnea and Preclinical Cardiac Damage: Need for U.S. Representative Study Sample , 2014 .

[80]  O. Ramilo,et al.  Respiratory syncytial virus: how, why and what to do. , 2014, The Journal of infection.

[81]  R. Peebles,et al.  Respiratory syncytial virus and reactive airway disease. , 2013, Current topics in microbiology and immunology.

[82]  S. Mukherjee,et al.  Innate immune responses to respiratory syncytial virus infection. , 2013, Current topics in microbiology and immunology.

[83]  R. Peebles Viral infections, atopy, and asthma: is there a causal relationship? , 2004, The Journal of allergy and clinical immunology.