Chapter 14 : Human Metapneumovirus

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Human Metapneumovirus, Page 1 of 2

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Human metapneumovirus (HMPV), a paramyxovirus first discovered in 2001, is a significant cause of respiratory tract disease in children and adults ( ). Humoral immunity plays an important role in HMPV infection, and the study of HMPV antibodies provides important clinical information including the seroprevalence of HMPV, age of primary infection, serological cross-protection between HMPV subgroups, evaluation of vaccine immunogenicity, and strategies for prophylaxis and therapy using monoclonal antibodies (mAbs).

Citation: Schuster J, Williams J. 2015. Human Metapneumovirus, p 237-247. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0020-2014
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Figure 1

Maximum clade credibility tree of HMPV and avian metapneumovirus (AMPV) F nucleotide diversity. Phylogenetic analysis of 85 full-length HMPV F nucleotide sequences from Canada (CAN), Japan (JPS or JPY), Tennessee (TN), or the Netherlands (NL) and 16 AMPV F sequences. The first two digits of the HMPV sequence names indicate the year of the isolate. The names of the AMPV sequences indicate geographic origin (US, United States; UK, United Kingdom; MN, Minnesota) and year. The posterior probability of divergence is indicated at each node. Scale bar represents time in years. Reprinted from reference with permission of the publisher http://creativecommons.org/licenses/by/2.0/legalcode.

Citation: Schuster J, Williams J. 2015. Human Metapneumovirus, p 237-247. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0020-2014
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Image of Figure 2
Figure 2

Schematic of HMPV and RSV F protein domain structures and relative location of MARM mutation sites. Indicated are the N terminus (N), signal peptide (SP), fusion peptide (FP), heptad repeat 1 (HR1), heptad repeat 2 (HR2), transmembrane domain (TM), and C terminus (C), as well as the F1 and F2 segments of the F protein. The amino acid positions that border domains (predicted) or cleavage sites and C termini (known) are indicated. Also depicted are the relative positions of the HMPV epitope group MARM mutations and corresponding MARM mutation sites on the RSV F protein. Reprinted with permission from Ulbrandt ND, Ji H, Patel NK, Barnes AS, Wilson S, Kiener PA, Suzich J, McCarthy MP. 2008. 3113–3118. Copyright 2008 Society for General Microbiology. Permission conveyed through Copyright Clearance Center, Inc.

Citation: Schuster J, Williams J. 2015. Human Metapneumovirus, p 237-247. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0020-2014
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1. van den Hoogen BG,, de Jong JC,, Groen J,, Kuiken T,, de Groot R,, Fouchier RA,, Osterhaus AD . 2001. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 7 : 719 724.[PubMed] [CrossRef]
2. Wolf DG,, Zakay-Rones Z,, Fadeela A,, Greenberg D,, Dagan R . 2003. High seroprevalence of human metapneumovirus among young children in Israel. J Infect Dis 188 : 1865 1867.[PubMed] [CrossRef]
3. Ebihara T,, Endo R,, Kikuta H,, Ishiguro N,, Yoshioka M,, Ma X,, Kobayashi K . 2003. Seroprevalence of human metapneumovirus in Japan. J Med Virol 70 : 281 283.[PubMed] [CrossRef]
4. Ebihara T,, Endo R,, Kikuta H,, Ishiguro N,, Ishiko H,, Hara M,, Takahashi Y,, Kobayashi K . 2004. Human metapneumovirus infection in Japanese children. J Clin Microbiol 42 : 126 132.[PubMed] [CrossRef]
5. Pavlin JA,, Hickey AC,, Ulbrandt N,, Chan YP,, Endy TP,, Boukhvalova MS,, Chunsuttiwat S,, Nisalak A,, Libraty DH,, Green S,, Rothman AL,, Ennis FA,, Jarman R,, Gibbons RV,, Broder CC . 2008. Human metapneumovirus reinfection among children in Thailand determined by ELISA using purified soluble fusion protein. J Infect Dis 198 : 836 842.[PubMed] [CrossRef]
6. Ebihara T,, Endo R,, Kikuta H,, Ishiguro N,, Ishiko H,, Kobayashi K . 2004. Comparison of the seroprevalence of human metapneumovirus and human respiratory syncytial virus. J Med Virol 72 : 304 306.[PubMed] [CrossRef]
7. Dunn SR,, Ryder AB,, Tollefson SJ,, Xu M,, Saville BR,, Williams JV . 2013. Seroepidemiologies of human metapneumovirus and respiratory syncytial virus in young children, determined with a new recombinant fusion protein enzyme-linked immunosorbent assay. Clin Vaccine Immunol 20 : 1654 1656.[PubMed] [CrossRef]
8. Falsey AR,, Erdman D,, Anderson LJ,, Walsh EE . 2003. Human metapneumovirus infections in young and elderly adults. J Infect Dis 187 : 785 790.[PubMed] [CrossRef]
9. Lusebrink J,, Wiese C,, Thiel A,, Tillmann RL,, Ditt V,, Muller A,, Schildgen O,, Schildgen V . 2010. High seroprevalence of neutralizing capacity against human metapneumovirus in all age groups studied in Bonn, Germany. Clin Vaccine Immunol 17 : 481 484.[PubMed] [CrossRef]
10. Okamoto M,, Sugawara K,, Takashita E,, Muraki Y,, Hongo S,, Nishimura H,, Matsuzaki Y . 2010. Longitudinal course of human metapneumovirus antibody titers and reinfection in healthy adults. J Med Virol 82 : 2092 2096.[PubMed] [CrossRef]
11. de Graaf M,, Osterhaus AD,, Fouchier RA,, Holmes EC . 2008. Evolutionary dynamics of human and avian metapneumoviruses. J Gen Virol 89 : 2933 2942.[PubMed] [CrossRef]
12. Yang CF,, Wang CK,, Tollefson SJ,, Lintao LD,, Liem A,, Chu M,, Williams JV . 2013. Human metapneumovirus G protein is highly conserved within but not between genetic lineages. Arch Virol 158 : 1245 1252.[PubMed] [CrossRef]
13. Yang CF,, Wang CK,, Tollefson SJ,, Piyaratna R,, Lintao LD,, Chu M,, Liem A,, Mark M,, Spaete RR,, Crowe JE Jr,, Williams JV . 2009. Genetic diversity and evolution of human metapneumovirus fusion protein over twenty years. Virol J 6 : 138. doi:10.1186/1743-422X-6-138. [PubMed] [CrossRef]
14. Alvarez R,, Jones LP,, Seal BS,, Kapczynski DR,, Tripp RA . 2004. Serological cross-reactivity of members of the Metapneumovirus genus. Virus Res 105 : 67 73.[PubMed] [CrossRef]
15. Luo L,, Sabara MI,, Li Y . 2009. Analysis of antigenic cross-reactivity between subgroup C avian pneumovirus and human metapneumovirus by using recombinant fusion proteins. Transbound Emerg Dis 56 : 303 310.[PubMed] [CrossRef]
16. Wyde PR,, Chetty SN,, Jewell AM,, Boivin G,, Piedra PA . 2003. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res 60 : 51 59.[PubMed] [CrossRef]
17. Williams JV,, Wang CK,, Yang CF,, Tollefson SJ,, House FS,, Heck JM,, Chu M,, Brown JB,, Lintao LD,, Quinto JD,, Chu D,, Spaete RR,, Edwards KM,, Wright PF,, Crowe JE Jr . 2006. The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience. J Infect Dis 193 : 387 395.[PubMed] [CrossRef]
18. Peret TC,, Boivin G,, Li Y,, Couillard M,, Humphrey C,, Osterhaus AD,, Erdman DD,, Anderson LJ . 2002. Characterization of human metapneumoviruses isolated from patients in North America. J Infect Dis 185 : 1660 1663.[PubMed] [CrossRef]
19. Skiadopoulos MH,, Biacchesi S,, Buchholz UJ,, Riggs JM,, Surman SR,, Amaro-Carambot E,, McAuliffe JM,, Elkins WR,, St Claire M,, Collins PL,, Murphy BR . 2004. 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 78 : 6927 6937.[PubMed] [CrossRef]
20. MacPhail M,, Schickli JH,, Tang RS,, Kaur J,, Robinson C,, Fouchier RA,, Osterhaus AD,, Spaete RR,, Haller AA . 2004. 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 85 : 1655 1663.[PubMed] [CrossRef]
21. van den Hoogen BG,, Herfst S,, de Graaf M,, Sprong L,, van Lavieren R,, van Amerongen G,, Yuksel S,, Fouchier RA,, Osterhaus AD,, de Swart RL . 2007. Experimental infection of macaques with human metapneumovirus induces transient protective immunity. J Gen Virol 88 : 1251 1259.[PubMed] [CrossRef]
22. Matsuzaki Y,, Itagaki T,, Abiko C,, Aoki Y,, Suto A,, Mizuta K . 2008. Clinical impact of human metapneumovirus genotypes and genotype-specific seroprevalence in Yamagata, Japan. J Med Virol 80 : 1084 1089.[PubMed] [CrossRef]
23. Cseke G,, Wright DW,, Tollefson SJ,, Johnson JE,, Crowe JE Jr,, Williams JV . 2007. Human metapneumovirus fusion protein vaccines that are immunogenic and protective in cotton rats. J Virol 81 : 698 707.[PubMed] [CrossRef]
24. Williams JV,, Chen Z,, Cseke G,, Wright DW,, Keefer CJ,, Tollefson SJ,, Hessell A,, Podsiad A,, Shepherd BE,, Sanna PP,, Burton DR,, Crowe JE Jr,, Williamson RA . 2007. A recombinant human monoclonal antibody to human metapneumovirus fusion protein that neutralizes virus in vitro and is effective therapeutically in vivo. J Virol 81 : 8315 8324.[PubMed] [CrossRef]
25. Ulbrandt ND,, Ji H,, Patel NK,, Barnes AS,, Wilson S,, Kiener PA,, Suzich J,, McCarthy MP . 2008. Identification of antibody neutralization epitopes on the fusion protein of human metapneumovirus. J Gen Virol 89 : 3113 3118.[PubMed] [CrossRef]
26. Ishiguro N,, Ebihara T,, Endo R,, Ma X,, Kikuta H,, Ishiko H,, Kobayashi K . 2004. High genetic diversity of the attachment (G) protein of human metapneumovirus. J Clin Microbiol 42 : 3406 3414.[PubMed] [CrossRef]
27. Endo R,, Ebihara T,, Ishiguro N,, Teramoto S,, Ariga T,, Sakata C,, Hayashi A,, Ishiko H,, Kikuta H . 2008. Detection of four genetic subgroup-specific antibodies to human metapneumovirus attachment (G) protein in human serum. J Gen Virol 89 : 1970 1977.[PubMed] [CrossRef]
28. Skiadopoulos MH,, Biacchesi S,, Buchholz UJ,, Amaro-Carambot E,, Surman SR,, Collins PL,, Murphy BR . 2006. Individual contributions of the human metapneumovirus F, G, and SH surface glycoproteins to the induction of neutralizing antibodies and protective immunity. Virology 345 : 492 501.[PubMed] [CrossRef]
29. Mok H,, Tollefson SJ,, Podsiad AB,, Shepherd BE,, Polosukhin VV,, Johnston RE,, Williams JV,, Crowe JE Jr . 2008. An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats. J Virol 82 : 11410 11418.[PubMed] [CrossRef]
30. Ryder AB,, Tollefson SJ,, Podsiad AB,, Johnson JE,, Williams JV . 2010. Soluble recombinant human metapneumovirus G protein is immunogenic but not protective. Vaccine 28 : 4145 4152.[PubMed] [CrossRef]
31. Williams JV,, Tollefson SJ,, Johnson JE,, Crowe JE Jr . 2005. The cotton rat (Sigmodon hispidus) is a permissive small animal model of human metapneumovirus infection, pathogenesis, and protective immunity. J Virol 79 : 10944 10951.[PubMed] [CrossRef]
32. Darniot M,, Pitoiset C,, Petrella T,, Aho S,, Pothier P,, Manoha C . 2009. Age-associated aggravation of clinical disease after primary metapneumovirus infection of BALB/c mice. J Virol 83 : 3323 3332.[PubMed] [CrossRef]
33. Falsey AR,, Hennessey PA,, Formica MA,, Criddle MM,, Biear JM,, Walsh EE . 2010. Humoral immunity to human metapneumovirus infection in adults. Vaccine 28 : 1477 1480.[PubMed] [CrossRef]
34. Darniot M,, Petrella T,, Aho S,, Pothier P,, Manoha C . 2005. Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice. Vaccine 23 : 4473 4480.[PubMed] [CrossRef]
35. Levy C,, Aerts L,, Hamelin ME,, Granier C,, Szecsi J,, Lavillette D,, Boivin G,, Cosset FL . 2013. Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice. Vaccine 31 : 2778 2785.[PubMed] [CrossRef]
36. Biacchesi S,, Skiadopoulos MH,, Yang L,, Lamirande EW,, Tran KC,, Murphy BR,, Collins PL,, Buchholz UJ . 2004. Recombinant human Metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. J Virol 78 : 12877 12887.[PubMed] [CrossRef]
37. Herfst S,, de Graaf M,, Schrauwen EJ,, Sprong L,, Hussain K,, van den Hoogen BG,, Osterhaus AD,, Fouchier RA . 2008. Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters. J Gen Virol 89 : 1553 1562.[PubMed] [CrossRef]
38. Liu P,, Shu Z,, Qin X,, Dou Y,, Zhao Y,, Zhao X . 2013. A live attenuated human metapneumovirus vaccine strain provides complete protection against homologous viral infection and cross-protection against heterologous viral infection in BALB/c mice. Clin Vaccine Immunol 20 : 1246 1254.[PubMed] [CrossRef]
39. Wei Y,, Zhang Y,, Cai H,, Mirza AM,, Iorio RM,, Peeples ME,, Niewiesk S,, Li J . 2014. Roles of the putative integrin-binding motif of the human metapneumovirus fusion (f) protein in cell-cell fusion, viral infectivity, and pathogenesis. J Virol 88 : 4338 4352.[PubMed] [CrossRef]
40. Cox RG,, Livesay SB,, Johnson M,, Ohi MD,, Williams JV . 2012. The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins. J Virol 86 : 12148 12160.[PubMed] [CrossRef]
41. Cseke G,, Maginnis MS,, Cox RG,, Tollefson SJ,, Podsiad AB,, Wright DW,, Dermody TS,, Williams JV . 2009. Integrin alphavbeta1 promotes infection by human metapneumovirus. Proc Natl Acad Sci USA 106 : 1566 1571.[PubMed] [CrossRef]
42. Talaat KR,, Karron RA,, Thumar B,, McMahon BA,, Schmidt AC,, Collins PL,, Buchholz UJ . 2013. Experimental infection of adults with recombinant wild-type human metapneumovirus. J Infect Dis 208 : 1669 1678.[PubMed] [CrossRef]
43. Yim KC,, Cragin RP,, Boukhvalova MS,, Blanco JC,, Hamlin ME,, Boivin G,, Porter DD,, Prince GA . 2007. Human metapneumovirus: enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged. Vaccine 25 : 5034 5040.[PubMed] [CrossRef]
44. de Swart RL,, van den Hoogen BG,, Kuiken T,, Herfst S,, van Amerongen G,, Yuksel S,, Sprong L,, Osterhaus AD . 2007. Immunization of macaques with formalin-inactivated human metapneumovirus induces hypersensitivity to hMPV infection. Vaccine 25 : 8518 8528.[PubMed] [CrossRef]
45. Tang RS,, Schickli JH,, MacPhail M,, Fernandes F,, Bicha L,, Spaete J,, Fouchier RA,, Osterhaus AD,, Spaete R,, Haller AA . 2003. 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 77 : 10819 10828.[PubMed] [CrossRef]
46. Tang RS,, Mahmood K,, Macphail M,, Guzzetta JM,, Haller AA,, Liu H,, Kaur J,, Lawlor HA,, Stillman EA,, Schickli JH,, Fouchier RA,, Osterhaus AD,, Spaete RR . 2005. A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys. Vaccine 23 : 1657 1667.[PubMed] [CrossRef]
47. Herfst S,, de Graaf M,, Schrauwen EJ,, Ulbrandt ND,, Barnes AS,, Senthil K,, Osterhaus AD,, Fouchier RA,, van den Hoogen BG . 2007. Immunization of Syrian golden hamsters with F subunit vaccine of human metapneumovirus induces protection against challenge with homologous or heterologous strains. J Gen Virol 88 : 2702 2709.[PubMed] [CrossRef]
48. Cox RG,, Erickson JJ,, Hastings AK,, Becker JC,, Johnson M,, Craven RE,, Tollefson SJ,, Boyd KL,, Williams JV . 2014. Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model. J Virol 88 : 6368 6379.[PubMed] [CrossRef]
49. Tedcastle AB,, Fenwick F,, Robinson MJ,, Toms GL . 2014. Immunogenicity in mice of human metapneumovirus with a truncated SH glycoprotein. J Med Virol 86 : 547 557.[PubMed] [CrossRef]
50. O’Shaughnessy L,, Carr M,, Crowley B,, Carberry S,, Doyle S . 2011. Recombinant expression and immunological characterisation of proteins derived from human metapneumovirus. J Clin Virol 52 : 236 243.[PubMed] [CrossRef]
51. Ishiguro N,, Ebihara T,, Endo R,, Ma X,, Kawai E,, Ishiko H,, Kikuta H . 2006. Detection of antibodies against human metapneumovirus by Western blot using recombinant nucleocapsid and matrix proteins. J Med Virol 78 : 1091 1095.[PubMed] [CrossRef]
52. Tedcastle AB,, Fenwick F,, Ingram RE,, King BJ,, Robinson MJ,, Toms GL . 2012. The characterization of monoclonal antibodies to human metapneumovirus and the detection of multiple forms of the virus nucleoprotein and phosphoprotein. J Med Virol 84 : 1061 1070.[PubMed] [CrossRef]
53. Pediatrics . 1998. 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 102 : 531537.
54. Ulbrandt ND,, Ji H,, Patel NK,, Riggs JM,, Brewah YA,, Ready S,, Donacki NE,, Folliot K,, Barnes AS,, Senthil K,, Wilson S,, Chen M,, Clarke L,, MacPhail M,, Li J,, Woods RM,, Coelingh K,, Reed JL,, McCarthy MP,, Pfarr DS,, Osterhaus AD,, Fouchier RA,, Kiener PA,, Suzich JA . 2006. Isolation and characterization of monoclonal antibodies which neutralize human metapneumovirus in vitro and in vivo. J Virol 80 : 7799 7806.[PubMed] [CrossRef]
55. Hamelin ME,, Gagnon C,, Prince GA,, Kiener P,, Suzich J,, Ulbrandt N,, Boivin G . 2010. Prophylactic and therapeutic benefits of a monoclonal antibody against the fusion protein of human metapneumovirus in a mouse model. Antiviral Res 88 : 31 37.[PubMed] [CrossRef]
56. Wen X,, Krause JC,, Leser GP,, Cox RG,, Lamb RA,, Williams JV,, Crowe JE Jr,, Jardetzky TS . 2012. Structure of the human metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site. Nat Struct Mol Biol 19 : 461 463.[PubMed] [CrossRef]
57. Corti D,, Bianchi S,, Vanzetta F,, Minola A,, Perez L,, Agatic G,, Guarino B,, Silacci C,, Marcandalli J,, Marsland BJ,, Piralla A,, Percivalle E,, Sallusto F,, Baldanti F,, Lanzavecchia A . 2013. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 501 : 439 443.[PubMed] [CrossRef]
58. Schuster JE,, Cox RG,, Hastings AK,, Boyd KL,, Wadia J,, Chen Z,, Burton DR,, Williamson RA,, Williams JV . 26 May 2014. A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis doi:10.1093/infdis/jiu307. [CrossRef]
59. McLellan JS,, Chen M,, Chang JS,, Yang Y,, Kim A,, Graham BS,, Kwong PD . 2010. Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J Virol 84 : 12236 12244.[PubMed] [CrossRef]

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