Human Metapneumovirus – Clinical Virology

Abstract

Human metapneumovirus (hMPV) is an increasingly recognised cause of respiratory tract infections, particularly in children, the elderly, those with preexisting pulmonary diseases and immunocompromised hosts. The increasing availability of nucleic acid testing has revolutionised our understanding of the pathogenesis, epidemiology, clinical and laboratory aspects of hMPV infection. Although hMPVā€specific antiviral therapy and vaccines are currently unavailable, it is anticipated that this will change in the near future.

Key Concepts

  • hMPV is a leading cause of acute respiratory tract infections.
  • Infection with hMPV generally occurs in the first 2 years of life, and exposure to hMPV is near universal by the age of 5.
  • hMPV infection is characterised by respiratory tract infection with wheeze.
  • hMPV is associated with admission for exacerbations of obstructive pulmonary disease and congestive heart.
  • Patients with haematological malignancies have a high mortality with hMPV.
  • Diagnosis should be confirmed with NAT on nasopharyngeal specimens.

Keywords: human metapneumovirus; respiratory virus; upper respiratory tract infection; lower respiratory tract infection; pneumonia

Figure 1. Human pathogens in the Paramyxoviridae family.
Figure 2. Human metapneumovirus.
Figure 3. Cytopathic effect and syncytial formation of HMPV in LLC_MK2 (rhesus monkey kidney epithelial) cell culture detected at 17 days of culture.
close

References

Ali A , Khowaja AR , Bashir MZ , et al. (2013) Role of human metapneumovirus, influenza A virus and respiratory syncytial virus in causing WHO‐defined severe pneumonia in children in a developing country. PLoS One 8 (9): e74756.

Baños‐Lara MDR , Harvey L , Mendoza A , et al. (2014) Impact and regulation of lambda interferon response in human metapneumovirus infection. Journal of Virology 89 (1): 730–742.

Bao X , Kolli D , Ren J , et al. (2013) Human metapneumovirus glycoprotein G disrupts mitochondrial signaling in airway epithelial cells. PLoS One 8 (4): e62568.

Benkouiten S , Charrel R , Belhouchat K , et al. (2013) Circulation of respiratory viruses among pilgrims during the 2012 Hajj pilgrimage. Clinical Infectious Diseases 57 (7): 992–1000.

Boivin G , Mackay I , Sloots TP , et al. (2004) Global genetic diversity of human metapneumovirus fusion gene. Emerging Infectious Diseases 10 (6): 1154–1157.

Boivin G , De Serres G , Hamelin M‐È , et al. (2007) An outbreak of severe respiratory tract infection due to human metapneumovirus in a long‐term care facility. Clinical Infectious Diseases 44 (9): 1152–1158.

Bruno R , Marsico S , Minini C , et al. (2009) Human metapneumovirus infection in a cohort of young asymptomatic subjects. New Microbiologica 32 (3): 297–301.

Cantais A , Mory O , Pillet S , et al. (2014) Epidemiology and microbiological investigations of community‐acquired pneumonia in children admitted at the emergency department of a university hospital. Journal of Clinical Virology 60 (4): 402–407.

Carr MJ , Waters A , Fenwick F , et al. (2008) Molecular epidemiology of human metapneumovirus in Ireland. Journal of Medical Virology 80 (3): 510–516.

Centers for Medicare & Medicaid services (2014) https://www.cms.gov/Research‐Statistics‐Data‐and‐Systems/Statistics‐Trends‐and‐Reports/DataCompendium/index.html (accessed 04 Jan 2016).

Céspedes PF , Gonzalez PA and Kalergis AM (2013) Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells. Immunology 139 (3): 366–376.

Chemaly RF , Shah DP and Boeckh MJ (2014) Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies. Clinical Infectious Diseases 59 (suppl 5): S344–S351.

Cox R and Williams J (2013) Breaking in: Human metapneumovirus fusion and entry. Viruses 5 (1): 192–210.

Dare R , Sanghavi S , Bullotta A , et al. (2007) Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis. Journal of Clinical Microbiology 45 (2): 548–552.

Debiaggi M , Canducci F , Sampaolo M , et al. (2006) Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. Journal of Infectious Diseases 194 (4): 474–478.

Dwyer DE , Osbourn M , Ratnamohan VM , Durrheim DN and McPhie KA (2009) Outbreak of human metapneumovirus infection in a residential aged care facility. Communicable Diseases Intelligence Quarterly Report 33 (1): 38.

Ebihara T , Endo R , Kikuta H , et al. (2003) Seroprevalence of human metapneumovirus in Japan. Journal of Medical Virology 70 (2): 281–283.

Edwards KM , Zhu Y , Griffin MR , et al. (2013) Burden of human metapneumovirus infection in young children. New England Journal of Medicine 368 (7): 633–643.

Englund JA , Boeckh M , Kuypers J , et al. (2006) Brief communication: fatal human metapneumovirus infection in stem‐cell transplant recipients. Annals of Internal Medicine 144 (5): 344–349.

Esper F , Martinello RA , Boucher D , et al. (2004) A 1‐year experience with human metapneumovirus in children aged. Journal of Infectious Diseases 189 (8): 1388–1396.

Falsey AR , Erdman D , Anderson LJ and Walsh EE (2003) Human metapneumovirus infections in young and elderly adults. Journal of Infectious Diseases 187 (5): 785–790.

Feng L , Li Z , Zhao S , et al. (2014) Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009–2013. PLoS One 9 (6): e99419.

Flight WG , Bright‐Thomas RJ , Tilston P , et al. (2014) Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis. Thorax 69 (3): 247–253.

Hahn A , Wang W , Jaggi P , et al. (2013) Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages. Epidemiology and Infection 141 (10): 2213–2223.

Hamelin M‐È and Boivin G (2005) Human metapneumovirus: a ubiquitous and long‐standing respiratory pathogen. Pediatric Infectious Disease Journal 24 (11 Suppl): S203–S207.

Hamelin M‐È , Yim K , Kuhn KH , et al. (2005a) Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats. Journal of Virology 79 (14): 8894–8903.

Hamelin ME , Côté S , Laforge J , et al. (2005b) Human metapneumovirus infection in adults with community‐acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. Clinical Infectious Diseases 41 (4): 498–502.

Hayden FG (2013) Advances in antivirals for non‐influenza respiratory virus infections. Influenza and Other Respiratory Viruses 7: 36–43.

Herd KA , Mahalingam S , Mackay IM , et al. (2006) Cytotoxic T‐lymphocyte epitope vaccination protects against human metapneumovirus infection and disease in mice. Journal of Virology 80 (4): 2034–2044.

van den Hoogen BG , de Jong JC , et al. (2001) A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nature Medicine 7 (6): 719–724.

van den Hoogen BG , van Doornum GJJ , Fockens JC , et al. (2003) Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. Journal of Infectious Diseases 188 (10): 1571–1577.

van den Hoogen BG , van Boheemen S , de Rijck J , et al. (2014) Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction. Journal of General Virology 95 (Pt_8): 1625–1633.

Huck B , Egger M , Bertz H , Peyerl‐Hoffman G , et al. (2006) Human metapneumovirus infection in a hematopoietic stem cell transplant recipient with relapsed multiple myeloma and rapidly progressing lung cancer. Journal of Clinical Microbiology 44 (6): 2300–2303.

Johnstone J , Majumdar SR , Fox JD and Marrie TJ (2008) Human metapneumovirus pneumonia in adults: results of a prospective study. Clinical Infectious Diseases 46 (4): 571–574.

Jroundi I , Mahraoui C , Benmessaoud R , et al. (2014) Risk factors for a poor outcome among children admitted with clinically severe pneumonia to a university hospital in Rabat, Morocco. International Journal of Infectious Diseases 28: 164–170.

Kamboj M , Gerbin M , Huang C‐K , et al. (2008) Clinical characterization of human metapneumovirus infection among patients with cancer. Journal of Infection 57 (6): 464–471.

Kim S , Sung H , Im HJ , Hong S‐J and Kim M‐N (2009) Molecular epidemiological investigation of a nosocomial outbreak of human metapneumovirus infection in a pediatric hemato‐oncology patient population. Journal of Clinical Microbiology 47 (4): 1221–1224.

Klein MB , Yang H , DelBalso L , et al. (2010) Viral pathogens including human metapneumovirus are the primary cause of febrile respiratory illness in HIV‐infected adults receiving antiretroviral therapy. Journal of Infectious Diseases 201 (2): 297–301.

Kolli D , Gupta MR , Sbrana E , et al. (2014) Alveolar macrophages contribute to the pathogenesis of human metapneumovirus infection while protecting against respiratory syncytial virus infection. American Journal of Respiratory Cell and Molecular Biology 51 (4): 502–515.

Lai S‐H , Liao S‐L , Wong K‐S and Lin T‐Y (2014) Preceding human metapneumovirus infection increases adherence of Streptococcus pneumoniae and severity of murine pneumococcal pneumonia. Journal of Microbiology, Immunology and Infection XX: 1–9.

Lambert SB , Allen KM , Druce JD , et al. (2007) Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool‐aged children using parent‐collected specimens. Pediatrics 120 (4): e929–e937.

Larcher C , Geltner C , Fischer H , et al. (2005) Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. Journal of Heart and Lung Transplantation 24 (11): 1891–1901.

Li IWS , To KKW , Tang BSF , et al. (2008) Human metapneumovirus infection in an immunocompetent adult presenting as mononucleosis‐like illness. Journal of Infection 56 (5): 389–392.

Liao RS , Appelgate DM and Pelz RK (2012) An outbreak of severe respiratory tract infection due to human metapneumovirus in a long‐term care facility for the elderly in Oregon. Journal of Clinical Virology 53 (2): 171–173.

Louie JK , Schnurr DP , Pan C‐Y , et al. (2007) A summer outbreak of human metapneumovirus infection in a long‐term‐care facility. Journal of Infectious Diseases 196 (5): 705–708.

Mackay IM , Bialasiewicz S , Jacob KC , et al. (2006) Genetic diversity of human metapneumovirus over 4 consecutive years in Australia. Journal of Infectious Diseases 193 (12): 1630–1633.

Maggi F , Pifferi M , Vatteroni M , et al. (2003) Human metapneumovirus associated with respiratory tract infections in a 3‐year study of nasal swabs from infants in Italy. Journal of Clinical Microbiology 41 (7): 2987–2991.

Mahony JB (2008) Detection of respiratory viruses by molecular methods. Clinical Microbiology Reviews 21 (4): 716–747.

Marr KA , Carter RA , Boeckh M , Martin P and Corey L (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: Changes in epidemiology and risk factors. Blood 100 (13): 4358–4366.

Martinello RA , Esper F , Weibel C , et al. (2006) Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease. Journal of Infection 53 (4): 248–254.

Martino R , Porras RP , Rabella N , et al. (2005) Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biology of Blood and Marrow Transplantation 11 (10): 781–796.

Matsuzaki Y , Itagaki T , Ikeda T , et al. (2012) Human metapneumovirus infection among family members. Epidemiology and Infection 141 (04): 827–832.

Neemuchwala A , Duvvuri VR , Marchand‐Austin A , Li A and Gubbay JB (2014) Human metapneumovirus prevalence and molecular epidemiology in respiratory outbreaks in Ontario, Canada. Journal of Medical Virology 87 (2): 269–274.

Niizuma T , Okumura A , Kinoshita K and Shimizu T (2014) Acute encephalopathy associated with human metapneumovirus infection. Japanese Journal of Infectious Diseases 67 (3): 213–215.

Nissen MD , Siebert DJ , Mackay IM , Sloots TP and Withers SJ (2002) Evidence of human metapneumovirus in Australian children. Medical Journal of Australia 176 (4): 188.

Papenburg J , Hamelin M‐È , Ouhoummane N , et al. (2012) Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. Journal of Infectious Diseases 206 (2): 178–189.

Papenburg J , Carbonneau J , Isabel S , et al. (2013) Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade. Journal of Clinical Virology 58 (3): 541–547.

Peiris JSM , Tang W‐H , Chan K‐H , et al. (2003) Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerging Infectious Diseases 9 (6): 628–633.

Pitoiset C , Darniot M , Huet F , et al. (2010) Human metapneumovirus genotypes and severity of disease in young children (n = 100) during a 7‐year study in Dijon hospital, France. Journal of Medical Virology 82 (10): 1782–1789.

Ratnamohan VM , Taylor J , Zeng F , et al. (2014) Pandemic clinical case definitions are non‐specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia. Virology Journal 11: 113.

Regev L , Meningher T , Hindiyeh M , Mendelson E and Mandelboim M (2012) Increase human metapneumovirus mediated morbidity following pandemic influenza infection. PLoS One 7 (4): e34750.

Reiche J , Jacobsen S , Neubauer K , et al. (2014) Human metapneumovirus: insights from a ten‐year molecular and epidemiological analysis in Germany. PLoS One 9 (2): e88342.

Renaud C , Xie H , Seo S , et al. (2013) Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biology of Blood and Marrow Transplantation 19 (8): 1220–1226.

Rossignol JF and El‐Gohary YM (2006) Nitazoxanide in the treatment of viral gastroenteritis: a randomized double‐blind placebo‐controlled clinical trial. Alimentary Pharmacology and Therapeutics 24 (10): 1423–1430.

Roussy J‐F , Carbonneau J , Ouakki M , et al. (2014) Human metapneumovirus viral load is an important risk factor for disease severity in young children. Journal of Clinical Virology 60 (2): 133–140.

Schildgen V , van den Hoogen B , Fouchier R , et al. (2011) Human metapneumovirus: lessons learned over the first decade. Clinical Microbiology Reviews 24 (4): 734–754.

Seo YB , Song JY , Choi MJ , et al. (2014) Etiology and clinical outcomes of acute respiratory virus infection in hospitalized adults. Infection and Chemotherapy 46 (2): 67.

Sloots TP , Mackay IM , Bialasiewicz S , et al. (2006) Human metapneumovirus, Australia, 2001–2004. Emerging Infectious Diseases 12 (8): 1263–1266.

Souza JS , Watanabe A , Carraro E , Granato C and Bellei N (2012) Severe metapneumovirus infections among immunocompetent and immunocompromised patients admitted to hospital with respiratory infection. Journal of Medical Virology 85 (3): 530–536.

Stockton J , Stephenson I , Fleming D and Zambon M (2002) Human metapneumovirus as a cause of community‐acquired respiratory illness. Emerging Infectious Diseases 8 (9): 897–901.

Sumino KC , Agapov E , Pierce RA , et al. (2005) Detection of severe human metapneumovirus infection by real‐time polymerase chain reaction and histopathological assessment. Journal of Infectious Diseases 192 (6): 1052–1060.

Tu C‐C , Chen L‐K , Lee Y‐S , et al. (2008) An outbreak of human metapneumovirus infection in hospitalized psychiatric adult patients in Taiwan. Scandinavian Journal of Infectious Diseases 41 (5): 363–367.

Turunen R , Koistinen A , Vuorinen T , et al. (2015) The first wheezing episode: respiratory virus etiology, atopic characteristics, and illness severity. Pediatric Allergy and Immunology 25 (8): 796–803.

Velez Rueda AJ , Mistchenko AS and Viegas M (2013) Phylogenetic and phylodynamic analyses of human metapneumovirus in buenos aires (Argentina) for a three‐year period (2009–2011). PLoS One 8 (4): e63070.

Vicente D , Montes M , Cilla G , Perez‐Yarza EG and Perez‐Trallero E (2006) Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. Clinical Infectious Diseases 42 (12): e111–e113.

Walsh EE , Peterson DR and Falsey AR (2008) Human metapneumovirus infections in adults: another piece of the puzzle. JAMA Internal Medicine 168 (22): 2489–2496.

Wei H‐Y , Tsao K‐C , Huang C‐G , Huang Y‐C and Lin T‐Y (2013) Clinical features of different genotypes/genogroups of human metapneumovirus in hospitalized children. Journal of Microbiology, Immunology and Infection 46 (5): 352–357.

Weinberg A , Lyu DM , Li S , Marquesen J and Zamora MR (2010) Incidence and morbidity of human metapneumovirus and other community‐acquired respiratory viruses in lung transplant recipients. Transplant Infectious Disease 12 (4): 330–335.

Wen SC and Williams JV (2015) New approaches for immunization and therapy against human metapneumovirus. Clinical and Vaccine Immunology 22 (8): 858–866.

Widmer K , Zhu Y , Williams JV , et al. (2012) Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. Journal of Infectious Diseases 206 (1): 56–62.

Wierik M , Nguyen D , Beersma M , et al. (2012) An outbreak of severe respiratory tract infection caused by human metapneumovirus in a residential care facility for elderly in Utrecht, the Netherlands, January to March 2010. Eurosurveillance 17: 1–7.

Williams JV , Harris PA , Tollefson SJ , et al. (2004) Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. New England Journal of Medicine 350 (5): 443–450.

Williams JV , Crowe JE , Enriquez R , et al. (2005a) Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults. Journal of Infectious Diseases 192 (7): 1149–1153.

Williams JV , Martino R , Rabella N , et al. (2005b) A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections. Journal of Infectious Diseases 192 (6): 1061–1065.

Wyde PR , Chetty SN , Jewell AM , Boivin G and Piedra PA (2003) Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Research 60 (1): 51–59.

Zhang D , He Z , Xu L , et al. (2014) Epidemiology characteristics of respiratory viruses found in children and adults with respiratory tract infections in southern China. International Journal of Infectious Diseases 25: 159–164.

Further Reading

Falsey AR (2015) Human metapneumovirus. In: Mandell GL , Bennett JE and Dolin R (eds) Mandel, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th edn. Philadelphia: Churchill Livingstone.

Rawling J and Melero JA (2011) Respiratory syncytial virus. In: Encyclopedia of Life Sciences. Chichester: John Wiley & Sons, Ltd. http://www.els.net [doi: 10.1002/9780470015902.a0000429.pub3].

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Keighley, Caitlin L, Kok, Jen, Nissen, Michael D, and Dwyer, Dominic E(Mar 2016) Human Metapneumovirus – Clinical Virology. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023617]