Metapneumovirus Infections and Respiratory Complications

Susanna Esposito; Maria Vincenza Mastrolia

doi:10.1055/s-0036-1584800

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2016; 37(04): 512-521
DOI: 10.1055/s-0036-1584800

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Metapneumovirus Infections and Respiratory Complications

Susanna Esposito

¹Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

,

Maria Vincenza Mastrolia

¹Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

› Author Affiliations

Abstract

Acute respiratory tract infections (ARTIs) are the most common illnesses experienced by people of all ages worldwide. In 2001, a new respiratory pathogen called human metapneumovirus (hMPV) was identified in respiratory secretions. hMPV is an RNA virus of the Paramyxoviridae family, and it has been isolated on every continent and from individuals of all ages. hMPV causes 7 to 19% of all cases of ARTIs in both hospitalized and outpatient children, and the rate of detection in adults is approximately 3%. Symptoms of hMPV infection range from a mild cold to a severe disease requiring a ventilator and cardiovascular support. The main risk factors for severe disease upon hMPV infection are the presence of a high viral load, coinfection with other agents (especially human respiratory syncytial virus), being between 0 and 5 months old or older than 65 years, and immunodeficiency. Currently, available treatments for hMPV infections are only supportive, and antiviral drugs are employed in cases of severe disease as a last resort. Ribavirin and immunoglobulins have been used in some patients, but the real efficacy of these treatments is unclear. At present, the direction of research on therapy for hMPV infection is toward the development of new approaches, and a variety of vaccination strategies are being explored and tested in animal models. However, further studies are required to define the best treatment and prevention strategies.

Keywords

acute respiratory tract infections - human metapneumovirus - human metapneumovirus infection - human metapneumovirus vaccine

Full Text

References

References
1 Walker CL, Rudan I, Liu L , et al. Global burden of childhood pneumonia and diarrhoea. Lancet 2013; 381 (9875) 1405-1416
2 United Nations Children's Fund. Committing to child survival: A promise renewed Progress report 2014. UNICEF, 2014. Available at: www.apromiserenewed.org
3 Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of world-wide distribution of child deaths from acute respiratory infections. Lancet Infect Dis 2002; 2 (1) 25-32
4 Weigl JA, Puppe W, Gröndahl B, Schmitt HJ. Epidemiological investigation of nine respiratory pathogens in hospitalized children in Germany using multiplex reverse-transcriptase polymerase chain reaction. Eur J Clin Microbiol Infect Dis 2000; 19 (5) 336-343
5 van den Hoogen BG, de Jong JC, Groen J , et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 2001; 7 (6) 719-724
6 van den Hoogen BG, Herfst S, Sprong L , et al. Antigenic and genetic variability of human metapneumoviruses. Emerg Infect Dis 2004; 10 (4) 658-666
7 van den Hoogen BG, Bestebroer TM, Osterhaus AD, Fouchier RA. Analysis of the genomic sequence of a human metapneumovirus. Virology 2002; 295 (1) 119-132
8 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
9 Chano F, Rousseau C, Laferrière C, Couillard M, Charest H. Epidemiological survey of human metapneumovirus infection in a large pediatric tertiary care center. J Clin Microbiol 2005; 43 (11) 5520-5525
10 Esper F, Boucher D, Weibel C, Martinello RA, Kahn JS. 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
11 Adams O, Weis J, Jasinska K, Vogel M, Tenenbaum T. Comparison of human metapneumovirus, respiratory syncytial virus and Rhinovirus respiratory tract infections in young children admitted to hospital. J Med Virol 2015; 87 (2) 275-280
12 Abdullah Brooks W, Erdman D, Terebuh P , et al. Human metapneumovirus infection among children, Bangladesh. Emerg Infect Dis 2007; 13 (10) 1611-1613
13 Sloots TP, Mackay IM, Bialasiewicz S , et al. Human metapneumovirus, Australia, 2001-2004. Emerg Infect Dis 2006; 12 (8) 1263-1266
14 Barbosa Ramirez J, Pulido Dominguez P, Rey Benito G, Mendez Rico J, Castellanos J, Páez Martinez A. Human respiratory syncytial virus and metapneumovirus in patients with acute respiratory infection in Colombia, 2000 - 2011. Rev Panam Salud Publica 2014; 36 (2) 101-109
15 Gerna G, Campanini G, Rovida F , et al. Changing circulation rate of human metapneumovirus strains and types among hospitalized pediatric patients during three consecutive winter-spring seasons. Brief report. Arch Virol 2005; 150 (11) 2365-2375
16 Papenburg J, Carbonneau J, Isabel S , et al. Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade. J Clin Virol 2013; 58 (3) 541-547
17 Kahn JS. Epidemiology of human metapneumovirus. Clin Microbiol Rev 2006; 19 (3) 546-557
18 Panda S, Mohakud NK, Pena L, Kumar S. Human metapneumovirus: review of an important respiratory pathogen. Int J Infect Dis 2014; 25: 45-52
19 Edwards KM, Zhu Y, Griffin MR , et al; New Vaccine Surveillance Network. Burden of human metapneumovirus infection in young children. N Engl J Med 2013; 368 (7) 633-643
20 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
21 Williams JV, Harris PA, Tollefson SJ , et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 2004; 350 (5) 443-450
22 Osterback R, Peltola V, Jartti T, Vainionpää R. Human metapneumovirus infections in children. Emerg Infect Dis 2008; 14 (1) 101-106
23 Leung J, Esper F, Weibel C, Kahn JS. 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
24 van den Hoogen BG, van Doornum GJ, Fockens JC , et al. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis 2003; 188 (10) 1571-1577
25 McAdam AJ, Hasenbein ME, Feldman HA , et al. Human metapneumovirus in children tested at a tertiary-care hospital. J Infect Dis 2004; 190 (1) 20-26
26 Mullins JA, Erdman DD, Weinberg GA , et al. Human metapneumovirus infection among children hospitalized with acute respiratory illness. Emerg Infect Dis 2004; 10 (4) 700-705
27 van den Hoogen BG, Osterhaus DM, Fouchier RA. Clinical impact and diagnosis of human metapneumovirus infection. Pediatr Infect Dis J 2004; 23 (1, Suppl): S25-S32
28 Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis 2003; 187 (5) 785-790
29 Martinello RA, Esper F, Weibel C, Ferguson D, Landry ML, Kahn JS. Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease. J Infect 2006; 53 (4) 248-254
30 van den Hoogen BG. Respiratory tract infection due to human metapneumovirus among elderly patients. Clin Infect Dis 2007; 44 (9) 1159-1160
31 Thammawat S, Sadlon TA, Hallsworth PG, Gordon DL. Role of cellular glycosaminoglycans and charged regions of viral G protein in human metapneumovirus infection. J Virol 2008; 82 (23) 11767-11774
32 Schowalter RM, Chang A, Robach JG, Buchholz UJ, Dutch RE. Low-pH triggering of human metapneumovirus fusion: essential residues and importance in entry. J Virol 2009; 83 (3) 1511-1522
33 Vargas SO, Kozakewich HP, Perez-Atayde AR, McAdam AJ. 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
34 Schildgen O, Simon A, Williams J. Animal models for human metapneumovirus (HMPV) infections. Vet Res 2007; 38 (1) 117-126
35 Sumino KC, Agapov E, Pierce RA , 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
36 Schildgen O, Glatzel T, Geikowski T , et al. Human metapneumovirus RNA in encephalitis patient. Emerg Infect Dis 2005; 11 (3) 467-470
37 Laham FR, Israele V, Casellas JM , et al. Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy. J Infect Dis 2004; 189 (11) 2047-2056
38 Gaunt E, McWilliam-Leitch EC, 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
39 Ordás J, Boga JA, Alvarez-Argüelles M , et al. Role of metapneumovirus in viral respiratory infections in young children. J Clin Microbiol 2006; 44 (8) 2739-2742
40 Qaisy LM, Meqdam MM, Alkhateeb A, Al-Shorman A, Al-Rousan HO, Al-Mogbel MS. Human metapneumovirus in Jordan: prevalence and clinical symptoms in hospitalized pediatric patients and molecular virus characterization. Diagn Microbiol Infect Dis 2012; 74 (3) 288-291
41 Williams JV, Wang CK, Yang CF , 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
42 Pitoiset C, Darniot M, Huet F, Aho SL, Pothier P, Manoha C. Human metapneumovirus genotypes and severity of disease in young children (n = 100) during a 7-year study in Dijon hospital, France. J Med Virol 2010; 82 (10) 1782-1789
43 Ali SA, Williams JV, Chen Q , et al. Human metapneumovirus in hospitalized children in Amman, Jordan. J Med Virol 2010; 82 (6) 1012-1016
44 Wolf DG, 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
45 Chonmaitree T, Heikkinen T. Role of viruses in middle-ear disease. Ann N Y Acad Sci 1997; 830: 143-157
46 Heikkinen T, Thint M, Chonmaitree T. Prevalence of various respiratory viruses in the middle ear during acute otitis media. N Engl J Med 1999; 340 (4) 260-264
47 Williams JV, Tollefson SJ, Nair S, Chonmaitree T. Association of human metapneumovirus with acute otitis media. Int J Pediatr Otorhinolaryngol 2006; 70 (7) 1189-1193
48 Arnold JC, Singh KK, Milder E , et al. Human metapneumovirus associated with central nervous system infection in children. Pediatr Infect Dis J 2009; 28 (12) 1057-1060
49 Webster DL, Gardner AH, Dye TJ, Chima RS. Status epilepticus: a possible association with human metapneumovirus infection. Pediatrics 2014; 133 (3) e747-e750
50 Walsh EE, Peterson DR, Falsey AR. Human metapneumovirus infections in adults: another piece of the puzzle. Arch Intern Med 2008; 168 (22) 2489-2496
51 Williams JV, 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
52 Rohde G, Borg I, Arinir U , et al. Relevance of human metapneumovirus in exacerbations of COPD. Respir Res 2005; 6: 150
53 Hamelin ME, 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
54 Boivin G, De Serres G, Hamelin ME , 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
55 Spaeder MC, Custer JW, Bembea MM, Aganga DO, Song X, Scafidi S. A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus. Pediatr Crit Care Med 2013; 14 (3) 268-272
56 Paget SP, Andresen DN, Kesson AM, Egan JR. Comparison of human metapneumovirus and respiratory syncytial virus in children admitted to a paediatric intensive care unit. J Paediatr Child Health 2011; 47 (10) 737-741
57 Hahn A, Wang W, Jaggi P , et al. Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages. Epidemiol Infect 2013; 141 (10) 2213-2223
58 Estrada B, Carter M, Barik S, Vidal R, Herbert D, Ramsey KM. Severe human metapneumovirus infection in hospitalized children. Clin Pediatr (Phila) 2007; 46 (3) 258-262
59 Schlapbach LJ, Agyeman P, Hutter D, Aebi C, Wagner BP, Riedel T. Human metapneumovirus infection as an emerging pathogen causing acute respiratory distress syndrome. J Infect Dis 2011; 203 (2) 294-295, author reply 296
60 Ulloa-Gutierrez R, Skippen P, Synnes A , et al. Life-threatening human metapneumovirus pneumonia requiring extracorporeal membrane oxygenation in a preterm infant. Pediatrics 2004; 114 (4) e517-e519
61 Contentin L, Guillon A, Garot D, Gaudy-Graffin C, Perrotin D. Acute respiratory distress syndrome secondary to human metapneumovirus infection in a young healthy adult. Intensive Care Med 2013; 39 (3) 533-534
62 Haas LE, de Rijk NX, Thijsen SF. Human metapneumovirus infections on the ICU: a report of three cases. Ann Intensive Care 2012; 2 (1) 30
63 Roussy JF, Carbonneau J, Ouakki M , et al. Human metapneumovirus viral load is an important risk factor for disease severity in young children. J Clin Virol 2014; 60 (2) 133-140
64 Bosis S, Esposito S, Osterhaus AD , et al. Association between high nasopharyngeal viral load and disease severity in children with human metapneumovirus infection. J Clin Virol 2008; 42 (3) 286-290
65 Peng D, Zhao X, Liu E , et al. Analysis of viral load in children infected with human metapneumovirus. Iran J Pediatr 2010; 20 (4) 393-400
66 Vicente D, Montes M, Cilla G, Perez-Yarza EG, Perez-Trallero E. Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. Clin Infect Dis 2006; 42 (12) e111-e113
67 Matsuzaki Y, Itagaki T, Abiko C, Aoki Y, Suto A, Mizuta K. Clinical impact of human metapneumovirus genotypes and genotype-specific seroprevalence in Yamagata, Japan. J Med Virol 2008; 80 (6) 1084-1089
68 Wei HY, Tsao KC, Huang CG, Huang YC, Lin TY. Clinical features of different genotypes/genogroups of human metapneumovirus in hospitalized children. J Microbiol Immunol Infect 2013; 46 (5) 352-357
69 Agapov E, Sumino KC, Gaudreault-Keener M, Storch GA, Holtzman MJ. 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
70 Bach N, Cuvillon D, Brouard J , et al. Acute respiratory tract infections due to a human metapneumovirus in children: descriptive study and comparison with respiratory syncytial virus infections [in French]. Arch Pediatr 2004; 11 (3) 212-215
71 Bosis S, Esposito S, Niesters HG, Crovari P, Osterhaus AD, Principi N. Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses. J Med Virol 2005; 75 (1) 101-104
72 Esper F, Martinello RA, Boucher D , et al. A 1-year experience with human metapneumovirus in children aged <5 years. J Infect Dis 2004; 189 (8) 1388-1396
73 Semple MG, 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
74 Madhi SA, Ludewick H, Kuwanda L , et al. Pneumococcal coinfection with human metapneumovirus. J Infect Dis 2006; 193 (9) 1236-1243
75 Boeckh M, Erard V, Zerr D, Englund J. Emerging viral infections after hematopoietic cell transplantation. Pediatr Transplant 2005; 9 (Suppl. 07) 48-54
76 Kamboj M, Gerbin M, Huang CK , et al. Clinical characterization of human metapneumovirus infection among patients with cancer. J Infect 2008; 57 (6) 464-471
77 Godet C, Le Goff J, Beby-Defaux A , et al. Human metapneumovirus pneumonia in patients with hematological malignancies. J Clin Virol 2014; 61 (4) 593-596
78 Larcher C, Geltner C, Fischer H, Nachbaur D, Müller LC, Huemer HP. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant 2005; 24 (11) 1891-1901
79 Madhi SA, Ludewick H, Abed Y, Klugman KP, Boivin G. Human metapneumovirus-associated lower respiratory tract infections among hospitalized human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected African infants. Clin Infect Dis 2003; 37 (12) 1705-1710
80 Weinberg A, Lyu DM, Li S, Marquesen J, Zamora MR. Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients. Transpl Infect Dis 2010; 12 (4) 330-335
81 Egli A, Bucher C, Dumoulin A , et al. Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation. Infection 2012; 40 (6) 677-684
82 Dokos C, Masjosthusmann K, Rellensmann G , et al. Fatal human metapneumovirus infection following allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2013; 15 (3) E97-E101
83 Renaud C, Xie H, Seo S , et al. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol Blood Marrow Transplant 2013; 19 (8) 1220-1226
84 Debur MC, Vidal LR, Stroparo E , et al. Human metapneumovirus infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis 2010; 12 (2) 173-179
85 Chu HY, Renaud C, Ficken E, Thomson B, Kuypers J, Englund JA. Respiratory tract infections due to human metapneumovirus in immunocompromised children. J Pediatric Infect Dis Soc 2014; 3 (4) 286-293
86 Papenburg J, Hamelin ME, Ouhoummane N , et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis 2012; 206 (2) 178-189
87 Williams JV, Tollefson SJ, Heymann PW, Carper HT, Patrie J, Crowe JE. Human metapneumovirus infection in children hospitalized for wheezing. J Allergy Clin Immunol 2005; 115 (6) 1311-1312
88 Williams JV, Crowe Jr JE, 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
89 Kwon JM, Shim JW, Kim DS, Jung HL, Park MS, Shim JY. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations. Korean J Pediatr 2014; 57 (1) 29-34
90 Jartti T, van den Hoogen B, Garofalo RP, Osterhaus AD, Ruuskanen O. Metapneumovirus and acute wheezing in children. Lancet 2002; 360 (9343) 1393-1394
91 García-García ML, Calvo C, Casas I , et al. Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5. Pediatr Pulmonol 2007; 42 (5) 458-464
92 Takeyama A, Hashimoto K, Sato M , et al. Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years. Eur J Pediatr 2014; 173 (7) 959-966
93 Inoue Y, Shimojo N. Epidemiology of virus-induced wheezing/asthma in children. Front Microbiol 2013; 4: 391
94 Honda H, Iwahashi J, Kashiwagi T , et al. Outbreak of human metapneumovirus infection in elderly inpatients in Japan. J Am Geriatr Soc 2006; 54 (1) 177-180
95 Ilvan A, Aslan G, Serin MS , et al. Investigation of the presence of human metapneumovirus in patients with chronic obstructive pulmonary disease and asthma and its relationship with the attacks [in Turkish]. Mikrobiyol Bul 2013; 47 (4) 636-649
96 Vicente D, Montes M, Cilla G, Pérez-Trallero E. Human metapneumovirus and chronic obstructive pulmonary disease. Emerg Infect Dis 2004; 10 (7) 1338-1339
97 Po JL, Gardner EM, Anaraki F, Katsikis PD, Murasko DM. Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection. Mech Ageing Dev 2002; 123 (8) 1167-1181
98 Stout-Delgado HW, Du W, Shirali AC, Booth CJ, Goldstein DR. Aging promotes neutrophil-induced mortality by augmenting IL-17 production during viral infection. Cell Host Microbe 2009; 6 (5) 446-456
99 Skiadopoulos MH, Biacchesi S, Buchholz UJ , 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
100 Tollefson SJ, Cox RG, Williams JV. Studies of culture conditions and environmental stability of human metapneumovirus. Virus Res 2010; 151 (1) 54-59
101 Reina J, Ferres F, Alcoceba E, Mena A, de Gopegui ER, Figuerola J. Comparison of different cell lines and incubation times in the isolation by the shell vial culture of human metapneumovirus from pediatric respiratory samples. J Clin Virol 2007; 40 (1) 46-49
102 Schildgen V, Lüsebrink J, Ditt V , et al. Human HepG2 cells support respiratory syncytial virus and human metapneumovirus replication. J Virol Methods 2010; 163 (1) 74-81
103 Maertzdorf J, Wang CK, Brown JB , et al. Real-time reverse transcriptase PCR assay for detection of human metapneumoviruses from all known genetic lineages. J Clin Microbiol 2004; 42 (3) 981-986
104 Bellau-Pujol S, Vabret A, Legrand L , et al. Development of three multiplex RT-PCR assays for the detection of 12 respiratory RNA viruses. J Virol Methods 2005; 126 (1–2) 53-63
105 Bharaj P, Sullender WM, Kabra SK , et al. Respiratory viral infections detected by multiplex PCR among pediatric patients with lower respiratory tract infections seen at an urban hospital in Delhi from 2005 to 2007. Virol J 2009; 6: 89
106 Choudhary ML, Anand SP, Heydari M , et al. Development of a multiplex one step RT-PCR that detects eighteen respiratory viruses in clinical specimens and comparison with real time RT-PCR. J Virol Methods 2013; 189 (1) 15-19
107 Liu L, Bastien N, Sidaway F, Chan E, Li Y. Seroprevalence of human metapneumovirus (hMPV) in the Canadian province of Saskatchewan analyzed by a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay. J Med Virol 2007; 79 (3) 308-313
108 Okamoto M, Sugawara K, Takashita E , et al. Development and evaluation of a whole virus-based enzyme-linked immunosorbent assay for the detection of human metapneumovirus antibodies in human sera. J Virol Methods 2010; 164 (1–2) 24-29
109 Prins JM, Wolthers KC. Human metapneumovirus: a new pathogen in children and adults. Neth J Med 2004; 62 (6) 177-179
110 Broor S, Bharaj P, Chahar HS. Human metapneumovirus: a new respiratory pathogen. J Biosci 2008; 33 (4) 483-493
111 Principi N, Bosis S, Esposito S. Human metapneumovirus in paediatric patients. Clin Microbiol Infect 2006; 12 (4) 301-308
112 Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol 2006; 16 (1) 37-48
113 Bonney D, Razali H, Turner A, Will A. Successful treatment of human metapneumovirus pneumonia using combination therapy with intravenous ribavirin and immune globulin. Br J Haematol 2009; 145 (5) 667-669
114 Park SY, Baek S, Lee SO , et al. Efficacy of oral ribavirin in hematologic disease patients with paramyxovirus infection: analytic strategy using propensity scores. Antimicrob Agents Chemother 2013; 57 (2) 983-989
115 Kitanovski L, Kopriva S, Pokorn M , et al. Treatment of severe human metapneumovirus (hMPV) pneumonia in an immunocompromised child with oral ribavirin and IVIG. J Pediatr Hematol Oncol 2013; 35 (7) e311-e313
116 Raza K, Ismailjee SB, 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
117 Hamelin ME, Couture C, Sackett M , et al. The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice. Antivir Ther 2008; 13 (1) 39-46
118 Hamelin ME, Gagnon C, Prince GA , et al. Prophylactic and therapeutic benefits of a monoclonal antibody against the fusion protein of human metapneumovirus in a mouse model. Antiviral Res 2010; 88 (1) 31-37
119 Williams IG. Enfuvirtide (Fuzeon): the first fusion inhibitor. Int J Clin Pract 2003; 57 (10) 890-897
120 Cianci C, Meanwell N, Krystal M. Antiviral activity and molecular mechanism of an orally active respiratory syncytial virus fusion inhibitor. J Antimicrob Chemother 2005; 55 (3) 289-292
121 Deffrasnes C, Hamelin ME, Prince GA, Boivin G. Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus. Antimicrob Agents Chemother 2008; 52 (1) 279-287
122 Deffrasnes C, Cavanagh MH, Goyette N , et al. Inhibition of human metapneumovirus replication by small interfering RNA. Antivir Ther 2008; 13 (6) 821-832
123 Hamelin ME, Couture C, Sackett MK, Boivin G. Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus. J Gen Virol 2007; 88 (Pt 12): 3391-3400
124 Yim KC, Cragin RP, Boukhvalova MS , et al. Human metapneumovirus: enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged. Vaccine 2007; 25 (27) 5034-5040
125 Anderson LJ, Dormitzer PR, Nokes DJ, Rappuoli R, Roca A, Graham BS. Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine 2013; 31 (Suppl. 02) B209-B215
126 Lévy C, Aerts L, Hamelin ME , et al. Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice. Vaccine 2013; 31 (25) 2778-2785
127 Cox RG, Erickson JJ, Hastings AK , et al. Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model. J Virol 2014; 88 (11) 6368-6379
128 Herfst S, Schrauwen EJ, de Graaf M , et al. Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques. Vaccine 2008; 26 (33) 4224-4230
129 Biacchesi S, Pham QN, Skiadopoulos MH, Murphy BR, Collins PL, Buchholz UJ. 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
130 Talaat KR, Karron RA, Thumar B , et al. Experimental infection of adults with recombinant wild-type human metapneumovirus. J Infect Dis 2013; 208 (10) 1669-1678