Human Metapneumovirus

Céline Deffrasnes; Marie-Ève Hamelin; Guy Boivin

doi:10.1055/s-2007-976493

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2007; 28(2): 213-221
DOI: 10.1055/s-2007-976493

Human Metapneumovirus

Céline Deffrasnes¹ ^, ² , Marie-Ève Hamelin¹ ^, ² , Guy Boivin¹ ^, ²

¹Department of Medical Biology, Faculty of Medicine, Laval University, Quebec, Canada
²Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec, Quebec, Canada

Abstract

ABSTRACT

Human metapneumovirus (hMPV) is a newly discovered paramyxovirus associated with upper and lower respiratory tract infections most commonly in young children, elderly subjects, and immunocompromised patients. hMPV can cause severe infections such as bronchiolitis and pneumonia and is responsible for 5 to 10% of hospitalizations of children suffering from acute respiratory tract infections. Such infections are indistinguishable from those caused by human respiratory syncytial virus. The first hMPV infection occurs during early childhood but reinfections are common throughout life, especially in older subjects. Molecular methods such as reverse transcriptase polymerase chain reaction (RT-PCR) are the preferred diagnostic modality due to fastidious growth in cell culture. Promising experimental models have been developed to better understand hMPV pathogenesis and to evaluate the potential effect of different therapeutic modalities. No commercial treatments are yet available for hMPV, although ribavirin has shown activity both in vitro and in animal models. Live attenuated vaccines produced by reverse genetics have also shown good efficacy in animals.

KEYWORDS

Human metapneumovirus - pneumonia - bronchiolitis - respiratory diseases

Volltext

Referenzen

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; 7 719-724
2 Ebihara T, Endo R, Kikuta H et al.. Seroprevalence of human metapneumovirus in Japan. J Med Virol. 2003; 70 281-283
3 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 1865-1867
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 1660-1663
5 Noyola D E, Rodriguez-Moreno G, Sanchez-Alvarado J, Martinez-Wagner R, Ochoa-Zavala J R. Viral etiology of lower respiratory tract infections in hospitalized children in Mexico. Pediatr Infect Dis J. 2004; 23 118-123
6 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
7 Galiano M, Videla C, Puch S S, Martinez A, Echavarria M, Carballal G. Evidence of human metapneumovirus in children in Argentina. J Med Virol. 2004; 72 299-303
8 Cuevas L E, Nasser A M, Dove W, Gurgel R Q, Greensill J, Hart C A. Human metapneumovirus and respiratory syncytial virus, Brazil. Emerg Infect Dis. 2003; 9 1626-1628
9 Mirazo S, Ruchansky D, Blanc A, Arbiza J. Serologic evidence of human metapneumovirus circulation in Uruguay. Mem Inst Oswaldo Cruz. 2005; 100 715-718
10 Gray G C, Capuano A W, Setterquist S F et al.. Human metapneumovirus, Peru. Emerg Infect Dis. 2006; 12 347-350
11 von Linstow M L, Henrik Larsen H, Eugen-Olsen J et al.. Human metapneumovirus and respiratory syncytial virus in hospitalized Danish children with acute respiratory tract infection. Scand J Infect Dis. 2004; 36 578-584
12 Christensen A, Nordbo S A, Jeansson S, Slordahl S. Lower respiratory tract infection caused by human metapneumovirus in two children: the first report of human metapneumovirus infection in Norway. Scand J Infect Dis. 2003; 35 772-774
13 Stockton J, Stephenson I, Fleming D, Zambon M. Human metapneumovirus as a cause of community-acquired respiratory illness. Emerg Infect Dis. 2002; 8 897-901
14 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 2987-2991
15 Jartti T, van den Hoogen B, Garofalo R P, Osterhaus A D, Ruuskanen O. Metapneumovirus and acute wheezing in children. Lancet. 2002; 360 1393-1394
16 Freymouth F, Vabret A, Legrand L et al.. Presence of the new human metapneumovirus in French children with bronchiolitis. Pediatr Infect Dis J. 2003; 22 92-94
17 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; 9 628-633
18 Thanasugarn W, Samransamruajkit R, Vanapongtipagorn P et al.. Human metapneumovirus infection in Thai children. Scand J Infect Dis. 2003; 35 754-756
19 Madhi S A, Ludewick H, Abed Y, Klugman K P, 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 1705-1710
20 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; 176 188
21 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; 295 119-132
22 Hall C B. Respiratory syncytial virus and parainfluenza virus. N Engl J Med. 2001; 344 1917-1928
23 Biacchesi S, Skiadopoulos M H, Boivin G et al.. Genetic diversity between human metapneumovirus subgroups. Virology. 2003; 315 1-9
24 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; 345 492-501
25 Boivin G, Mackay I, Sloots T P et al.. Global genetic diversity of human metapneumovirus fusion gene. Emerg Infect Dis. 2004; 10 1154-1157
26 Mackay I M, Bialasiewicz S, Waliuzzaman Z et al.. Use of the P gene to genotype human metapneumovirus identifies 4 viral subtypes. J Infect Dis. 2004; 190 1913-1918
27 van den Hoogen B G, Herfst S, Sprong L et al.. Antigenic and genetic variability of human metapneumoviruses. Emerg Infect Dis. 2004; 10 658-666
28 Huck B, Scharf G, Neumann-Haefelin D, Puppe W, Weigl J, Falcone V. Novel human metapneumovirus sublineage. Emerg Infect Dis. 2006; 12 147-150
29 Ishiguro N, Ebihara T, Endo R et al.. High genetic diversity of the attachment (G) protein of human metapneumovirus. J Clin Microbiol. 2004; 42 3406-3414
30 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 6927-6937
31 Vicente D, Montes M, Cilla G, Perez-Yarza E G, Perez-Trallero E. Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. Clin Infect Dis. 2006; 42 e111-e113
32 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; 193 396-403
33 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 1330-1334
34 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; 193 387-395
35 Bastien N, Ward D, Van Caeseele P et al.. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003; 41 4642-4646
36 Boivin G, De Serres G, Cote S et al.. Human metapneumovirus infections in hospitalized children. Emerg Infect Dis. 2003; 9 634-640
37 Bouscambert-Duchamp M, Lina B, Trompette A, Moret H, Motte J, Andreoletti L. Detection of human metapneumovirus RNA sequences in nasopharyngeal aspirates of young French children with acute bronchiolitis by real-time reverse transcriptase PCR and phylogenetic analysis. J Clin Microbiol. 2005; 43 1411-1414
38 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 1388-1396
39 McAdam A J, Hasenbein M E, Feldman H A et al.. Human metapneumovirus in children tested at a tertiary-care hospital. J Infect Dis. 2004; 190 20-26
40 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; 10 700-705
41 Nicholson K G, McNally T, Silverman M, Simons P, Stockton J D, Zambon M C. Rates of hospitalisation for influenza, respiratory syncytial virus and human metapneumovirus among infants and young children. Vaccine. 2006; 24 102-108
42 van den Hoogen B G, van Doornum G J, Fockens J C et al.. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis. 2003; 188 1571-1577
43 Viazov S, Ratjen F, Scheidhauer R, Fiedler M, Roggendorf M. High prevalence of human metapneumovirus infection in young children and genetic heterogeneity of the viral isolates. J Clin Microbiol. 2003; 41 3043-3045
44 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; 350 443-450
45 Ordas J, Boga J A, Alvarez-Arguelles M et al.. Role of metapneumovirus in viral respiratory infections in young children. J Clin Microbiol. 2006; 44 2739-2742
46 IJpma F F, Beekhuis D, Cotton M F et al.. Human metapneumovirus infection in hospital referred South African children. J Med Virol. 2004; 73 486-493
47 Sloots T P, Mackay I M, Bialasiewicz S et al.. Human metapneumovirus, Australia, 2001-2004. Emerg Infect Dis. 2006; 12 1263-1266
48 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 1213-1219
49 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; 12 249-253
50 Hamelin M E, Cote 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; 41 498-502
51 Pelletier G, Dery P, Abed Y, Boivin G. Respiratory tract reinfections by the new human metapneumovirus in an immunocompromised child. Emerg Infect Dis. 2002; 8 976-978
52 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 5944-5946
53 Morrow B M, Hatherill M, Smuts H E, Yeats J, Pitcher R, Argent A C. Clinical course of hospitalised children infected with human metapneumovirus and respiratory syncytial virus. J Paediatr Child Health. 2006; 42 174-178
54 Ebihara T, Endo R, Kikuta H et al.. Human metapneumovirus infection in Japanese children. J Clin Microbiol. 2004; 42 126-132
55 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; 8 285-293
56 Regev L, Hindiyeh M, Shulman L M et al.. Characterization of human metapneumovirus infections in Israel. J Clin Microbiol. 2006; 44 1484-1489
57 Chano F, Rousseau C, Laferriere C, Couillard M, Charest H. Epidemiological survey of human metapneumovirus infection in a large pediatric tertiary care center. J Clin Microbiol. 2005; 43 5520-5525
58 Kahn J S. Epidemiology of human metapneumovirus. Clin Microbiol Rev. 2006; 19 546-557
59 Robinson J L, Lee B E, Bastien N, Li Y. Seasonality and clinical features of human metapneumovirus infection in children in Northern Alberta. J Med Virol. 2005; 76 98-105
60 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(Suppl 1) S25-S32
61 Williams J V, Tollefson S J, Nair S, Chonmaitree T. Association of human metapneumovirus with acute otitis media. Int J Pediatr Otorhinolaryngol. 2006; 70 1189-1193
62 Schildgen O, Geikowski T, Glatzel T, Schuster J, Simon A. Frequency of human metapneumovirus in the upper respiratory tract of children with symptoms of an acute otitis media. Eur J Pediatr. 2005; 164 400-401
63 Schildgen O, Simon A. Induction of acute otitis media by human metapneumovirus. Pediatr Infect Dis J. 2005; 24 1126
64 Crowe Jr J E. Human metapneumovirus as a major cause of human respiratory tract disease. Pediatr Infect Dis J. 2004; 23(Suppl 11) S215-S221
65 Bosis S, Esposito S, Niesters H G, Crovari P, Osterhaus A D, Principi N. Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses. J Med Virol. 2005; 75 101-104
66 Foulongne V, Guyon G, Rodiere M, Segondy M. Human metapneumovirus infection in young children hospitalized with respiratory tract disease. Pediatr Infect Dis J. 2006; 25 354-359
67 Falsey A R, Erdman D, Anderson L J, Walsh E E. Human metapneumovirus infections in young and elderly adults. J Infect Dis. 2003; 187 785-790
68 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 1149-1153
69 Rohde G, Borg I, Arinir U et al.. Relevance of human metapneumovirus in exacerbations of COPD. Respir Res. 2005; 6 150
70 Hamelin M E, Prince G A, Gomez A M, Kinkead R, Boivin G. Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice. J Infect Dis. 2006; 193 1634-1642
71 Larcher C, Geltner C, Fischer H, Nachbaur D, Muller L C, Huemer H P. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant. 2005; 24 1891-1901
72 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 1052-1060
73 Englund J A, Boeckh M, Kuypers J et al.. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. 2006; 144 344-349
74 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; 31 309-310
75 Debiaggi M, Canducci F, Sampaolo M et al.. Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. J Infect Dis. 2006; 194 474-478
76 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; 9 372-375
77 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; 191 382-386
78 van Woensel J B, Bos A P, Lutter R, Rossen J W, Schuurman R. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection. Pediatr Pulmonol. 2006; 41 872-874
79 Lazar I, Weibel C, Dziura J, Ferguson D, Landry M L, Kahn J S. Human metapneumovirus and severity of respiratory syncytial virus disease. Emerg Infect Dis. 2004; 10 1318-1320
80 Sasaki A, Suzuki H, Saito R et al.. Prevalence of human metapneumovirus and influenza virus infections among Japanese children during two successive winters. Pediatr Infect Dis J. 2005; 24 905-908
81 Chan P K, Tam J S, Lam C W et al.. Human metapneumovirus detection in patients with severe acute respiratory syndrome. Emerg Infect Dis. 2003; 9 1058-1063
82 Poutanen S M, Low D E, Henry B et al.. Identification of severe acute respiratory syndrome in Canada. N Engl J Med. 2003; 348 1995-2005
83 Fouchier R A, Kuiken T, Schutten M et al.. Aetiology: Koch's postulates fulfilled for SARS virus. Nature. 2003; 423 240
84 Schildgen O, Glatzel T, Geikowski T et al.. Human metapneumovirus RNA in encephalitis patient. Emerg Infect Dis. 2005; 11 467-470
85 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; 7 478-486
86 Kuiken T, van den Hoogen B G, van Riel D A et al.. Experimental human metapneumovirus infection of Cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract. Am J Pathol. 2004; 164 1893-1900
87 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 5848-5855
88 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; 34 320-329
89 Laham F R, Israele V, Casellas J M 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 2047-2056
90 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 14003-14011
91 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 8894-8903
92 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
93 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 10944-10951
94 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 57-66
95 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 10819-10828
96 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 5971-5978
97 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 14992-14997
98 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 4473-4480
99 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 10190-10199
100 Maertzdorf J, Wang C K, Brown J B et al.. Real-time reverse transcriptase PCR assay for detection of human metapneumoviruses from all known genetic lineages. J Clin Microbiol. 2004; 42 981-986
101 Cote S, Abed Y, Boivin G. Comparative evaluation of real-time PCR assays for detection of the human metapneumovirus. J Clin Microbiol. 2003; 41 3631-3635
102 Mackay I M, Jacob K C, Woolhouse D et al.. Molecular assays for detection of human metapneumovirus. J Clin Microbiol. 2003; 41 100-105
103 Deffrasnes C, Cote S, Boivin G. Analysis of replication kinetics of the human metapneumovirus in different cell lines by real-time PCR. J Clin Microbiol. 2005; 43 488-490
104 Hamelin M E, Abed Y, Boivin G. Human metapneumovirus: a new player among respiratory viruses. Clin Infect Dis. 2004; 38 983-990
105 Ingram R E, Fenwick F, McGuckin R, Tefari A, Taylor C, Toms G L. Detection of human metapneumovirus in respiratory secretions by reverse-transcriptase polymerase chain reaction, indirect immunofluorescence, and virus isolation in human bronchial epithelial cells. J Med Virol. 2006; 78 1223-1231
106 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 1138-1141
107 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 1950-1952
108 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; 35 113-116
109 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 3443-3446
110 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 7799-7806
111 Johnson S, Oliver C, Prince G A et al.. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis. 1997; 176 1215-1224
112 Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics. 1998; 102(3 Pt 1) 531-537
113 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 51-59
114 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; 50 774-777
115 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 51-59
116 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 12608-12613
117 Biacchesi S, Skiadopoulos M H, Tran K C, Murphy B R, Collins P L, Buchholz U J. Recovery of human metapneumovirus from cDNA: optimization of growth in vitro and expression of additional genes. Virology. 2004; 321 247-259
118 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 12877-12887
119 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 6588-6597
120 Pham Q N, Biacchesi S, Skiadopoulos M H, Murphy B R, Collins P L, Buchholz U J. Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo. J Virol. 2005; 79 15114-15122
121 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 1657-1667
122 Herd K A, Mahalingam S, Mackay I M, Nissen M, Sloots T P, Tindle R W. Cytotoxic T-lymphocyte epitope vaccination protects against human metapneumovirus infection and disease in mice. J Virol. 2006; 80 2034-2044

Guy BoivinM.D.

Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec, CHUQ-CHUL

Rm. RC-709, 2705 Blvd. Laurier, Sainte-Foy, Quebec, Canada G1V 4G2

eMail: guy.boivin@crchul.ulaval.ca