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Semin Respir Crit Care Med 2011; 32(4): 447-453
DOI: 10.1055/s-0031-1283284
© Thieme Medical Publishers

Human Metapneumovirus

Jing Lu Kroll1 , Adriana Weinberg1 , 2 , 3
  • 1Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado
  • 2Department of Pediatrics, University of Colorado Denver, Aurora, Colorado
  • 3Department of Pathology, University of Colorado Denver, Aurora, Colorado
Further Information

Publication History

Publication Date:
19 August 2011 (online)

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ABSTRACT

Human metapneumovirus (hMPV) is a common pathogen that can cause both upper and lower respiratory tract infections, particularly in children, elderly adults, and immunocompromised hosts. Since its initial identification in 2001, hMPV has been isolated from individuals with acute respiratory tract infections (ARTIs) in virtually every continent. Serological studies indicate that it has caused human infection since 1958 or earlier. The epidemiology and clinical manifestations of hMPV are similar to those of the human respiratory syncytial virus (hRSV). HMPV has a seasonal variation: it circulates in late winter to early spring in temperate climates; late spring and summer in tropical regions. In young children, symptoms range from mild upper respiratory tract infections to severe lower respiratory tract infections (eg, bronchiolitis, croup, and pneumonia). In adults, hMPV reinfection typically presents with colds and flulike clinical manifestations. The disease is more severe (sometimes lethal) in immunocompromised hosts. Reverse transcription polymerase chain reaction (RT-PCR) is the most sensitive test with which to detect hMPV infection. Direct detection of hMPV antigens with an immunofluorescent antibody test is available but is less sensitive than PCR. Antibody testing is used mainly for retrospective diagnosis (≥ fourfold increase in titer or seroconversion) and for epidemiological studies. The mainstay of treatment of hMPV infections is supportive. Ribavirin has similar activity in vitro and in animal models against hRSV and hMPV, but its efficacy in vivo is unproven. Monoclonal antibodies have activity in murine models but are not available in humans. Several vaccines are promising in animal models, but their safety and efficacy have not yet been evaluated in humans.

KEYWORDS

Human metapneumovirus - paramyxovirus - respiratory viral infections

REFERENCES

  • 1 van den Hoogen B G, de Jong J C, Groen J et al.. A newly discovered human pneumovirus isolated from young children with respiratory tract disease.  Nat Med. 2001;  7 (6) 719-724
    CrossrefPubMedSearch in Google Scholar
  • 2 Ebihara T, Endo R, Kikuta H et al.. Seroprevalence of human metapneumovirus in Japan.  J Med Virol. 2003;  70 (2) 281-283
    CrossrefPubMedSearch in Google Scholar
  • 3 Nissen M D, Siebert D J, Mackay I M, Sloots T P, Withers S J. Evidence of human metapneumovirus in Australian children.  Med J Aust. 2002;  176 (4) 188
    PubMedSearch in Google Scholar
  • 4 Peret T C, Boivin G, Li Y et al.. Characterization of human metapneumoviruses isolated from patients in North America.  J Infect Dis. 2002;  185 (11) 1660-1663
    CrossrefPubMedSearch in Google Scholar
  • 5 Wolf D G, Zakay-Rones Z, Fadeela A, Greenberg D, Dagan R. High seroprevalence of human metapneumovirus among young children in Israel.  J Infect Dis. 2003;  188 (12) 1865-1867
    CrossrefPubMedSearch in Google Scholar
  • 6 Jartti T, van den Hoogen B, Garofalo R P, Osterhaus A D, Ruuskanen O. Metapneumovirus and acute wheezing in children.  Lancet. 2002;  360 (9343) 1393-1394
    CrossrefPubMedSearch in Google Scholar
  • 7 Stockton J, Stephenson I, Fleming D, Zambon M. Human metapneumovirus as a cause of community-acquired respiratory illness.  Emerg Infect Dis. 2002;  8 (9) 897-901
    CrossrefPubMedSearch in Google Scholar
  • 8 van den Hoogen B G, Bestebroer T M, Osterhaus A D, Fouchier R A. Analysis of the genomic sequence of a human metapneumovirus.  Virology. 2002;  295 (1) 119-132
    CrossrefPubMedSearch in Google Scholar
  • 9 Boivin G, Abed Y, Pelletier G et al.. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups.  J Infect Dis. 2002;  186 (9) 1330-1334
    CrossrefPubMedSearch in Google Scholar
  • 10 Biacchesi S, Skiadopoulos M H, Boivin G et al.. Genetic diversity between human metapneumovirus subgroups.  Virology. 2003;  315 (1) 1-9
    CrossrefPubMedSearch in Google Scholar
  • 11 Sumino K C, Agapov E, Pierce R A et al.. Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessment.  J Infect Dis. 2005;  192 (6) 1052-1060
    CrossrefPubMedSearch in Google Scholar
  • 12 Vargas S O, Kozakewich H P, Perez-Atayde A R, McAdam A J. Pathology of human metapneumovirus infection: insights into the pathogenesis of a newly identified respiratory virus.  Pediatr Dev Pathol. 2004;  7 (5) 478-486 discussion 421
    CrossrefPubMedSearch in Google Scholar
  • 13 Douville R N, Bastien N, Li Y, Pochard P, Simons F E, HayGlass K T. Human metapneumovirus elicits weak IFN-gamma memory responses compared with respiratory syncytial virus.  J Immunol. 2006;  176 (10) 5848-5855
    PubMedSearch in Google Scholar
  • 14 Guerrero-Plata A, Casola A, Suarez G et al.. Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus.  Am J Respir Cell Mol Biol. 2006;  34 (3) 320-329
    PubMedSearch in Google Scholar
  • 15 MacPhail M, Schickli J H, Tang R S et al.. Identification of small-animal and primate models for evaluation of vaccine candidates for human metapneumovirus (hMPV) and implications for hMPV vaccine design.  J Gen Virol. 2004;  85 (Pt 6) 1655-1663
    CrossrefPubMedSearch in Google Scholar
  • 16 Hamelin M E, Yim K, Kuhn K H et al.. Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats.  J Virol. 2005;  79 (14) 8894-8903
    CrossrefPubMedSearch in Google Scholar
  • 17 Alvarez R, Harrod K S, Shieh W J, Zaki S, Tripp R A. Human metapneumovirus persists in BALB/c mice despite the presence of neutralizing antibodies.  J Virol. 2004;  78 (24) 14003-14011
    CrossrefPubMedSearch in Google Scholar
  • 18 Herd K A, Nelson M, Mahalingam S, Tindle R W. Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus.  J Gen Virol. 2010;  91 (Pt 5) 1302-1310
    CrossrefPubMedSearch in Google Scholar
  • 19 Skiadopoulos M H, Biacchesi S, Buchholz U J 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.  J Virol. 2004;  78 (13) 6927-6937
    CrossrefPubMedSearch in Google Scholar
  • 20 Tang R S, Schickli J H, MacPhail M et al.. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3′ proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity.  J Virol. 2003;  77 (20) 10819-10828
    CrossrefPubMedSearch in Google Scholar
  • 21 Williams J V, Tollefson S J, Johnson J E, Crowe Jr J E. The cotton rat (Sigmodon hispidus) is a permissive small animal model of human metapneumovirus infection, pathogenesis, and protective immunity.  J Virol. 2005;  79 (17) 10944-10951
    CrossrefPubMedSearch in Google Scholar
  • 22 Wyde P R, Chetty S N, Jewell A M, Schoonover S L, Piedra P A. Development of a cotton rat-human metapneumovirus (hMPV) model for identifying and evaluating potential hMPV antivirals and vaccines.  Antiviral Res. 2005;  66 (1) 57-66
    CrossrefPubMedSearch in Google Scholar
  • 23 Alvarez R, Tripp R A. The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice.  J Virol. 2005;  79 (10) 5971-5978
    CrossrefPubMedSearch in Google Scholar
  • 24 Darniot M, Petrella T, Aho S, Pothier P, Manoha C. Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice.  Vaccine. 2005;  23 (36) 4473-4480
    CrossrefPubMedSearch in Google Scholar
  • 25 Guerrero-Plata A, Baron S, Poast J S, Adegboyega P A, Casola A, Garofalo R P. Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections.  J Virol. 2005;  79 (16) 10190-10199
    CrossrefPubMedSearch in Google Scholar
  • 26 Guerrero-Plata A, Casola A, Garofalo R P. Human metapneumovirus induces a profile of lung cytokines distinct from that of respiratory syncytial virus.  J Virol. 2005;  79 (23) 14992-14997
    CrossrefPubMedSearch in Google Scholar
  • 27 Kolli D, Bataki E L, Spetch L et al.. T lymphocytes contribute to antiviral immunity and pathogenesis in experimental human metapneumovirus infection.  J Virol. 2008;  82 (17) 8560-8569
    CrossrefPubMedSearch in Google Scholar
  • 28 Graham B S, Bunton L A, Wright P F, Karzon D T. Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice.  J Clin Invest. 1991;  88 (3) 1026-1033
    CrossrefPubMedSearch in Google Scholar
  • 29 Osterhaus A, Fouchier R. Human metapneumovirus in the community.  Lancet. 2003;  361 (9361) 890-891
    CrossrefPubMedSearch in Google Scholar
  • 30 Døllner H, Risnes K, Radtke A, Nordbø S A. Outbreak of human metapneumovirus infection in Norwegian children.  Pediatr Infect Dis J. 2004;  23 (5) 436-440
    PubMedSearch in Google Scholar
  • 31 Peiris J S, Tang W H, Chan K H et al.. Children with respiratory disease associated with metapneumovirus in Hong Kong.  Emerg Infect Dis. 2003;  9 (6) 628-633
    CrossrefPubMedSearch in Google Scholar
  • 32 Williams J V, Harris P A, Tollefson S J et al.. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.  N Engl J Med. 2004;  350 (5) 443-450
    CrossrefPubMedSearch in Google Scholar
  • 33 Maggi F, Pifferi M, Vatteroni M et al.. Human metapneumovirus associated with respiratory tract infections in a 3-year study of nasal swabs from infants in Italy.  J Clin Microbiol. 2003;  41 (7) 2987-2991
    CrossrefPubMedSearch in Google Scholar
  • 34 Boivin G, De Serres G, Côté S et al.. Human metapneumovirus infections in hospitalized children.  Emerg Infect Dis. 2003;  9 (6) 634-640
    CrossrefPubMedSearch in Google Scholar
  • 35 Esper F, Martinello R A, Boucher D et al.. A 1-year experience with human metapneumovirus in children aged <5 years.  J Infect Dis. 2004;  189 (8) 1388-1396
    CrossrefPubMedSearch in Google Scholar
  • 36 Boivin G, De Serres G, Hamelin M E et al.. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility.  Clin Infect Dis. 2007;  44 (9) 1152-1158
    CrossrefPubMedSearch in Google Scholar
  • 37 Ebihara T, Endo R, Ishiguro N, Nakayama T, Sawada H, Kikuta H. Early reinfection with human metapneumovirus in an infant.  J Clin Microbiol. 2004;  42 (12) 5944-5946
    CrossrefPubMedSearch in Google Scholar
  • 38 Hamelin M E, Côté S, Laforge J et al.. Human metapneumovirus infection in adults with community-acquired pneumonia and exacerbation of chronic obstructive pulmonary disease.  Clin Infect Dis. 2005;  41 (4) 498-502
    CrossrefPubMedSearch in Google Scholar
  • 39 Ordás J, Boga J A, Alvarez-Argüelles M et al.. Role of metapneumovirus in viral respiratory infections in young children.  J Clin Microbiol. 2006;  44 (8) 2739-2742
    CrossrefPubMedSearch in Google Scholar
  • 40 Pelletier G, Déry P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child.  Emerg Infect Dis. 2002;  8 (9) 976-978
    CrossrefPubMedSearch in Google Scholar
  • 41 Williams J V, Wang C K, Yang C F et al.. The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience.  J Infect Dis. 2006;  193 (3) 387-395
    CrossrefPubMedSearch in Google Scholar
  • 42 Sloots T P, Mackay I M, Bialasiewicz S et al.. Human metapneumovirus, Australia, 2001-2004.  Emerg Infect Dis. 2006;  12 (8) 1263-1266
    CrossrefPubMedSearch in Google Scholar
  • 43 Mullins J A, Erdman D D, Weinberg G A et al.. Human metapneumovirus infection among children hospitalized with acute respiratory illness.  Emerg Infect Dis. 2004;  10 (4) 700-705
    CrossrefPubMedSearch in Google Scholar
  • 44 Wolf D G, Greenberg D, Shemer-Avni Y, Givon-Lavi N, Bar-Ziv J, Dagan R. Association of human metapneumovirus with radiologically diagnosed community-acquired alveolar pneumonia in young children.  J Pediatr. 2010;  156 (1) 115-120
    CrossrefPubMedSearch in Google Scholar
  • 45 Hamelin M E, Abed Y, Boivin G. Human metapneumovirus: a new player among respiratory viruses.  Clin Infect Dis. 2004;  38 (7) 983-990
    CrossrefPubMedSearch in Google Scholar
  • 46 Falsey A R, Erdman D, Anderson L J, Walsh E E. Human metapneumovirus infections in young and elderly adults.  J Infect Dis. 2003;  187 (5) 785-790
    CrossrefPubMedSearch in Google Scholar
  • 47 Walsh E E, Peterson D R, Falsey A R. Human metapneumovirus infections in adults: another piece of the puzzle.  Arch Intern Med. 2008;  168 (22) 2489-2496
    CrossrefPubMedSearch in Google Scholar
  • 48 Williams J V, Martino R, Rabella N et al.. A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections.  J Infect Dis. 2005;  192 (6) 1061-1065
    CrossrefPubMedSearch in Google Scholar
  • 49 Englund J A, Boeckh M, Kuypers J et al.. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients.  Ann Intern Med. 2006;  144 (5) 344-349
    CrossrefPubMedSearch in Google Scholar
  • 50 Oliveira R, Machado A, Tateno A, Boas L V, Pannuti C, Machado C. Frequency of human metapneumovirus infection in hematopoietic SCT recipients during 3 consecutive years.  Bone Marrow Transplant. 2008;  42 (4) 265-269
    CrossrefPubMedSearch in Google Scholar
  • 51 Weinberg A, Lyu D M, Li S, Marquesen J, Zamora M R. Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients.  Transpl Infect Dis. 2010;  12 (4) 330-335
    CrossrefPubMedSearch in Google Scholar
  • 52 Hopkins P, McNeil K, Kermeen F et al.. Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus.  Am J Respir Crit Care Med. 2008;  178 (8) 876-881
    CrossrefPubMedSearch in Google Scholar
  • 53 Gerna G, Vitulo P, Rovida F et al.. Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients.  J Med Virol. 2006;  78 (3) 408-416
    CrossrefPubMedSearch in Google Scholar
  • 54 Agapov E, Sumino K C, Gaudreault-Keener M, Storch G A, Holtzman M J. Genetic variability of human metapneumovirus infection: evidence of a shift in viral genotype without a change in illness.  J Infect Dis. 2006;  193 (3) 396-403
    CrossrefPubMedSearch in Google Scholar
  • 55 Boivin G, Mackay I, Sloots T P et al.. Global genetic diversity of human metapneumovirus fusion gene.  Emerg Infect Dis. 2004;  10 (6) 1154-1157
    CrossrefPubMedSearch in Google Scholar
  • 56 Mackay I M, Bialasiewicz S, Jacob K C et al.. Genetic diversity of human metapneumovirus over 4 consecutive years in Australia.  J Infect Dis. 2006;  193 (12) 1630-1633
    CrossrefPubMedSearch in Google Scholar
  • 57 Gaunt E, McWilliam-Leitch E C, Templeton K, Simmonds P. Incidence, molecular epidemiology and clinical presentations of human metapneumovirus; assessment of its importance as a diagnostic screening target.  J Clin Virol. 2009;  46 (4) 318-324
    CrossrefPubMedSearch in Google Scholar
  • 58 Mahalingam S, Schwarze J, Zaid A et al.. Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?.  Microbes Infect. 2006;  8 (1) 285-293
    CrossrefPubMedSearch in Google Scholar
  • 59 Kim S, Sung H, Im H J, Hong S J, Kim M N. Molecular epidemiological investigation of a nosocomial outbreak of human metapneumovirus infection in a pediatric hemato-oncology patient population.  J Clin Microbiol. 2009;  47 (4) 1221-1224
    CrossrefPubMedSearch in Google Scholar
  • 60 Tu C C, Chen L K, Lee Y S et al.. An outbreak of human metapneumovirus infection in hospitalized psychiatric adult patients in Taiwan.  Scand J Infect Dis. 2009;  41 (5) 363-367
    CrossrefPubMedSearch in Google Scholar
  • 61 Esper F, Boucher D, Weibel C, Martinello R A, Kahn J S. Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children.  Pediatrics. 2003;  111 (6 Pt 1) 1407-1410
    CrossrefPubMedSearch in Google Scholar
  • 62 Xepapadaki P, Psarras S, Bossios A et al.. Human metapneumovirus as a causative agent of acute bronchiolitis in infants.  J Clin Virol. 2004;  30 (3) 267-270
    CrossrefPubMedSearch in Google Scholar
  • 63 Greensill J, McNamara P S, Dove W, Flanagan B, Smyth R L, Hart C A. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis.  Emerg Infect Dis. 2003;  9 (3) 372-375
    CrossrefPubMedSearch in Google Scholar
  • 64 Semple M G, Cowell A, Dove W et al.. Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis.  J Infect Dis. 2005;  191 (3) 382-386
    CrossrefPubMedSearch in Google Scholar
  • 65 König B, König W, Arnold R, Werchau H, Ihorst G, Forster J. Prospective study of human metapneumovirus infection in children less than 3 years of age.  J Clin Microbiol. 2004;  42 (10) 4632-4635
    CrossrefPubMedSearch in Google Scholar
  • 66 Arnold J C, Singh K K, Milder E et al.. Human metapneumovirus associated with central nervous system infection in children.  Pediatr Infect Dis J. 2009;  28 (12) 1057-1060
    CrossrefPubMedSearch in Google Scholar
  • 67 Williams J V, Crowe Jr J E, Enriquez R et al.. Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults.  J Infect Dis. 2005;  192 (7) 1149-1153
    CrossrefPubMedSearch in Google Scholar
  • 68 Beckham J D, Cadena A, Lin J et al.. Respiratory viral infections in patients with chronic, obstructive pulmonary disease.  J Infect. 2005;  50 (4) 322-330
    CrossrefPubMedSearch in Google Scholar
  • 69 Vicente D, Montes M, Cilla G, Pérez-Trallero E. Human metapneumovirus and chronic obstructive pulmonary disease.  Emerg Infect Dis. 2004;  10 (7) 1338-1339
    CrossrefPubMedSearch in Google Scholar
  • 70 Martinello R A, Esper F, Weibel C, Ferguson D, Landry M L, Kahn J S. Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease.  J Infect. 2006;  53 (4) 248-254
    CrossrefPubMedSearch in Google Scholar
  • 71 Rohde G, Borg I, Arinir U et al.. Relevance of human metapneumovirus in exacerbations of COPD.  Respir Res. 2005;  6 150
    CrossrefPubMedSearch in Google Scholar
  • 72 Debiaggi M, Canducci F, Sampaolo M et al.. Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients.  J Infect Dis. 2006;  194 (4) 474-478
    CrossrefPubMedSearch in Google Scholar
  • 73 Cane P A, van den Hoogen B G, Chakrabarti S, Fegan C D, Osterhaus A D. Human metapneumovirus in a haematopoietic stem cell transplant recipient with fatal lower respiratory tract disease.  Bone Marrow Transplant. 2003;  31 (4) 309-310
    CrossrefPubMedSearch in Google Scholar
  • 74 Debur M C, Vidal L R, Stroparo E et al.. Human metapneumovirus infection in hematopoietic stem cell transplant recipients.  Transpl Infect Dis. 2010;  12 (2) 173-179
    CrossrefPubMedSearch in Google Scholar
  • 75 Larcher C, Geltner C, Fischer H, Nachbaur D, Müller L C, Huemer H P. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology.  J Heart Lung Transplant. 2005;  24 (11) 1891-1901
    CrossrefPubMedSearch in Google Scholar
  • 76 Fuenzalida L, Fabrega J, Blanco S et al.. Usefulness of two new methods for diagnosing metapneumovirus infections in children.  Clin Microbiol Infect. 2010;  16 (11) 1663-1668
    CrossrefPubMedSearch in Google Scholar
  • 77 Janssen K, Floré K, Piette A, Vankeerberghen A, Padalko E. Implementation of real-time RT-PCR for detection of human metapneumovirus and its comparison with enzyme immunoassay.  Arch Virol. 2010;  155 (2) 207-215
    CrossrefPubMedSearch in Google Scholar
  • 78 Jokela P, Piiparinen H, Luiro K, Lappalainen M. Detection of human metapneumovirus and respiratory syncytial virus by duplex real-time RT-PCR assay in comparison with direct fluorescent assay.  Clin Microbiol Infect. 2010;  16 (10) 1568-1573
    CrossrefPubMedSearch in Google Scholar
  • 79 Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H. Detection of human metapneumovirus antigens in nasopharyngeal secretions by an immunofluorescent-antibody test.  J Clin Microbiol. 2005;  43 (3) 1138-1141
    CrossrefPubMedSearch in Google Scholar
  • 80 Gerna G, Sarasini A, Percivalle E, Genini E, Campanini G, Grazia Revello M. Simultaneous detection and typing of human metapneumovirus strains in nasopharyngeal secretions and cell cultures by monoclonal antibodies.  J Clin Virol. 2006;  35 (1) 113-116
    CrossrefPubMedSearch in Google Scholar
  • 81 Landry M L, Ferguson D, Cohen S, Peret T C, Erdman D D. Detection of human metapneumovirus in clinical samples by immunofluorescence staining of shell vial centrifugation cultures prepared from three different cell lines.  J Clin Microbiol. 2005;  43 (4) 1950-1952
    CrossrefPubMedSearch in Google Scholar
  • 82 Percivalle E, Sarasini A, Visai L, Revello M G, Gerna G. Rapid detection of human metapneumovirus strains in nasopharyngeal aspirates and shell vial cultures by monoclonal antibodies.  J Clin Microbiol. 2005;  43 (7) 3443-3446
    CrossrefPubMedSearch in Google Scholar
  • 83 Matsuzaki Y, Takashita E, Okamoto M et al.. Evaluation of a new rapid antigen test using immunochromatography for detection of human metapneumovirus in comparison with real-time PCR assay.  J Clin Microbiol. 2009;  47 (9) 2981-2984
    CrossrefPubMedSearch in Google Scholar
  • 84 Deffrasnes C, Côté S, Boivin G. Analysis of replication kinetics of the human metapneumovirus in different cell lines by real-time PCR.  J Clin Microbiol. 2005;  43 (1) 488-490
    CrossrefPubMedSearch in Google Scholar
  • 85 Hamelin M E, Boivin G. Development and validation of an enzyme-linked immunosorbent assay for human metapneumovirus serology based on a recombinant viral protein.  Clin Diagn Lab Immunol. 2005;  12 (2) 249-253
    CrossrefPubMedSearch in Google Scholar
  • 86 Leung J, Esper F, Weibel C, Kahn J S. Seroepidemiology of human metapneumovirus (hMPV) on the basis of a novel enzyme-linked immunosorbent assay utilizing hMPV fusion protein expressed in recombinant vesicular stomatitis virus.  J Clin Microbiol. 2005;  43 (3) 1213-1219
    CrossrefPubMedSearch in Google Scholar
  • 87 Ebihara T, Endo R, Kikuta H et al.. Human metapneumovirus infection in Japanese children.  J Clin Microbiol. 2004;  42 (1) 126-132
    CrossrefPubMedSearch in Google Scholar
  • 88 van den Hoogen B G, Osterhaus D M, Fouchier R A. Clinical impact and diagnosis of human metapneumovirus infection.  Pediatr Infect Dis J. 2004;  23 (1, Suppl) S25-S32
    CrossrefPubMedSearch in Google Scholar
  • 89 Skiadopoulos M H, Biacchesi S, Buchholz U J et al.. Individual contributions of the human metapneumovirus F, G, and SH surface glycoproteins to the induction of neutralizing antibodies and protective immunity.  Virology. 2006;  345 (2) 492-501
    CrossrefPubMedSearch in Google Scholar
  • 90 Ulbrandt N D, Ji H, Patel N K et al.. Isolation and characterization of monoclonal antibodies which neutralize human metapneumovirus in vitro and in vivo.  J Virol. 2006;  80 (16) 7799-7806
    CrossrefPubMedSearch in Google Scholar
  • 91 Williams J V, Chen Z, Cseke G et al.. A recombinant human monoclonal antibody to human metapneumovirus fusion protein that neutralizes virus in vitro and is effective therapeutically in vivo.  J Virol. 2007;  81 (15) 8315-8324
    CrossrefPubMedSearch in Google Scholar
  • 92 Deffrasnes C, Hamelin M E, Prince G A, Boivin G. Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus.  Antimicrob Agents Chemother. 2008;  52 (1) 279-287
    CrossrefPubMedSearch in Google Scholar
  • 93 Wyde P R, Chetty S N, Jewell A M, Boivin G, Piedra P A. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro.  Antiviral Res. 2003;  60 (1) 51-59
    CrossrefPubMedSearch in Google Scholar
  • 94 Hamelin M E, Prince G A, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection.  Antimicrob Agents Chemother. 2006;  50 (2) 774-777
    CrossrefPubMedSearch in Google Scholar
  • 95 Raza K, Ismailjee S B, Crespo M et al.. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin.  J Heart Lung Transplant. 2007;  26 (8) 862-864
    CrossrefPubMedSearch in Google Scholar
  • 96 Spetch L, Bowlin T L, Casola A. Effect of NMSO3 treatment in a murine model of human metapneumovirus infection.  J Gen Virol. 2008;  89 (Pt 11) 2709-2712
    CrossrefPubMedSearch in Google Scholar
  • 97 Wyde P R, Moylett E H, Chetty S N, Jewell A, Bowlin T L, Piedra P A. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by NMSO3 in tissue culture assays.  Antiviral Res. 2004;  63 (1) 51-59
    CrossrefPubMedSearch in Google Scholar
  • 98 Tang R S, Mahmood K, Macphail M et al.. A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys.  Vaccine. 2005;  23 (14) 1657-1667
    CrossrefPubMedSearch in Google Scholar
  • 99 Herfst S, de Graaf M, Schrauwen E J et al.. Immunization of Syrian golden hamsters with F subunit vaccine of human metapneumovirus induces protection against challenge with homologous or heterologous strains.  J Gen Virol. 2007;  88 (Pt 10) 2702-2709
    CrossrefPubMedSearch in Google Scholar
  • 100 Cseke G, Wright D W, Tollefson S J, Johnson J E, Crowe Jr J E, Williams J V. Human metapneumovirus fusion protein vaccines that are immunogenic and protective in cotton rats.  J Virol. 2007;  81 (2) 698-707
    CrossrefPubMedSearch in Google Scholar
  • 101 Biacchesi S, Pham Q N, Skiadopoulos M H, Murphy B R, Collins P L, Buchholz U J. Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates.  J Virol. 2005;  79 (19) 12608-12613
    CrossrefPubMedSearch in Google Scholar
  • 102 Biacchesi S, Skiadopoulos M H, Yang L et al.. Recombinant human Metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate.  J Virol. 2004;  78 (23) 12877-12887
    CrossrefPubMedSearch in Google Scholar
  • 103 Buchholz U J, Biacchesi S, Pham Q N et al.. Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: effects on RNA synthesis, attenuation, and immunogenicity.  J Virol. 2005;  79 (11) 6588-6597
    CrossrefPubMedSearch in Google Scholar
  • 104 Herfst S, de Graaf M, Schrauwen E J et al.. Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters.  J Gen Virol. 2008;  89 (Pt 7) 1553-1562
    CrossrefPubMedSearch in Google Scholar

Adriana WeinbergM.D. 

Departments of Pediatrics, Medicine, and Pathology, University of Colorado Denver

Mail Stop 8604, 12700 E. 19th Ave., Rm. 11126, Aurora, CO 80045

Email: adriana.weinberg@ucdenver.edu