Human Metapneumovirus

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
• 2 Ebihara T, Endo R, Kikuta H et al.. Seroprevalence of human metapneumovirus in Japan.  J Med Virol. 2003;  70 (2) 281-283
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 10 Biacchesi S, Skiadopoulos M H, Boivin G et al.. Genetic diversity between human metapneumovirus subgroups.  Virology. 2003;  315 (1) 1-9
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 29 Osterhaus A, Fouchier R. Human metapneumovirus in the community.  Lancet. 2003;  361 (9361) 890-891
• 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
• 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
• 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
• 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
• 34 Boivin G, De Serres G, Côté S et al.. Human metapneumovirus infections in hospitalized children.  Emerg Infect Dis. 2003;  9 (6) 634-640
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 42 Sloots T P, Mackay I M, Bialasiewicz S et al.. Human metapneumovirus, Australia, 2001-2004.  Emerg Infect Dis. 2006;  12 (8) 1263-1266
• 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
• 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
• 45 Hamelin M E, Abed Y, Boivin G. Human metapneumovirus: a new player among respiratory viruses.  Clin Infect Dis. 2004;  38 (7) 983-990
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 71 Rohde G, Borg I, Arinir U et al.. Relevance of human metapneumovirus in exacerbations of COPD.  Respir Res. 2005;  6 150
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 87 Ebihara T, Endo R, Kikuta H et al.. Human metapneumovirus infection in Japanese children.  J Clin Microbiol. 2004;  42 (1) 126-132
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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