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Emerging Respiratory Pathogens: Insights into Human Metapneumovirus (hMPV) and Bocavirus in Acute Respiratory Tract Infections
Corresponding Author(s) : K.G. Sruthi
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 13 No. 1 (2025): 2025 Volume -13 - Issue 1
Abstract
Acute respiratory tract infections caused by various viral pathogens remain a dominant cause of global morbidity and mortality, profoundly affecting healthcare systems and vulnerable populations. Human metapneumovirus and human bocavirus have emerged as critical agents implicated in both endemic and epidemic settings, often presenting with overlapping clinical features and significant burdens in paediatric, elderly, and immune compromised groups. Their virological diversity, capacity for coinfections, and potential for severe outcomes have led to intensified research aimed at unravelling their molecular mechanisms and clinical impact. Diagnostic modalities for these pathogens have advanced considerably, incorporating sensitive molecular assays and metagenomics based approaches. Despite noteworthy progress in understanding their biology and epidemiology, therapeutic measures remain primarily supportive, and vaccine development continues to face challenges stemming from viral diversity and immune evasion strategies. This chapter provides a detailed and integrative review of human metapneumovirus and human bocavirus, beginning with their global epidemiological trends and delving into their virology, pathogenesis, clinical spectrum, and diagnostic complexities. It further examines emerging therapeutic and preventive paradigms, including the promise of novel antivirals and vaccine candidates. By highlighting gaps in current knowledge and exploring future research directions, this chapter underscores the necessity for comprehensive surveillance, innovative technologies, and collaborative efforts to reduce the burden of these pathogens on public health worldwide.
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- Boivin G, De Serres G, Côte S, Gilca R, Abed Y, Rochette L, Bergeron MG, Dery P. Human metapneumovirus infections in hospitalized children. Emerg Infect Dis. 2003;9(6):63440.
- van den Hoogen BG, van Doornum GJ, Fockens JC, Cornelissen JJ, Beyer WE, de Groot R, Osterhaus AD, Fouchier RA. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis. 2003;188(10):15717.
- Schildgen O, Simon A, Wilkesmann A, Schildgen V, Brockmann M, Söder G, Geikowski T, Glatzel T, Kupfer B, EisHübinger AM. Human bocavirus DNA in parvovirus B19–positive patients. Emerg Infect Dis. 2008;14(8):14113.
- Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, Vuorinen T, Waris M, Bjerkner A, TiveljungLindell A, van den Hoogen BG. Human bocavirus and acute wheezing in children. Clin Infect Dis. 2007;44(7):90410.
- Arnold JC, Singh KK, Spector SA, Sawyer MH. Human metapneumovirus in hospitalized children. N Engl J Med. 2003;349(5):44350.
- Mackay IM, Jacob KC, Woolhouse D, Waller K, Syrmis MW, Nissen MD, Sloots TP. Molecular assays for detection of human metapneumovirus. J Clin Microbiol. 2003;41(3):10014.
- Bastien N, Ward D, Van Caeseele P, Brandt K, Lee SH, McNabb G, Kliewer G, Marrie TJ, Burton L, Forward K, McDonald R. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003;41(10):46426.
- Calvo C, GarcíaGarcía ML, Blanco C, Pozo F, Flecha IC, PérezBreña P. Human metapneumovirus infection in children in Spain. Emerg Infect Dis. 2006;12(1):1268.
- Kesebir D, Vazquez M, Weibel C, Shapiro ED, Ferguson D, Landry ML, Kahn JS. Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus. J Infect Dis. 2006;194(9):127682.
- Mahony JB. Detection of respiratory viruses by molecular methods. Clin Microbiol Rev. 2008;21(4):71647.
- Midulla F, Scagnolari C, Bonci E, Pierangeli A, Antonelli G, De Angelis D, Berardi R, Selvaggi C, Moretti C. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child. 2010;95(1):3541.
- Kaplan NM, Dove W, AbdEldayem SA, AbuZeid AF, Shamoon HE, Hart CA. Human bocavirus infection among children, Jordan. Emerg Infect Dis. 2006;12(9):141820.
- Longtin J, Bastien M, Gilca R, Leblanc E, De Serres G, Bergeron MG, Boivin G. Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis. 2008;14(2):21721.
- Vicente D, Cilla G, Montes M, PérezYarza EG, PérezTrallero E. Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis. 2007;13(4):6368.
- Lüef C, Frischmuth T, Weissbrich B. Detection of human bocavirus in nasopharyngeal aspirates of children and adults with respiratory tract infections. Pediatr Infect Dis J. 2005;24(8):6813.
- Jin Y, Cheng W, Xu Z, Wu W, Xu M, Lu S, Jin M. High prevalence of human bocavirus 2 and its role in childhood acute gastroenteritis in China. J Clin Virol. 2011;52(3):2513.
- Lu X, Chittaganpitch M, Olsen SJ, Mackay IM, Sloots TP, Fry AM, Erdman DD. Realtime PCR assays for detection of bocavirus in human specimens. J Clin Microbiol. 2006;44(9):32315.
- Smuts HE, Hardie D. Human bocavirus in hospitalized children, South Africa. Emerg Infect Dis. 2006;12(9):14578.
- Pilger DA, Cantarelli VV, Amantea SL, Siqueira MM, Porto NS, Takahashi GA, Barth AL. Human metapneumovirus associated with respiratory infection in southern Brazil: molecular and epidemiological features. Arch Virol. 2009;154(6):92937.
- Esposito S, Zampiero A, Prada E, Montinaro V, Colombo C, Fossali E, Bosis S, Principi N. Clinical and epidemiological characteristics of children hospitalized for respiratory syncytial virus infection. J Med Virol. 2011;83(2):32430.
- Biacchesi S, Skiadopoulos MH, Boivin G, Hanson CT, Murphy BR, Collins PL, Buchholz UJ. Genetic diversity between human metapneumovirus subgroups. Virology. 2003;315(1):19.
- Kapoor A, Simmonds P, Slikas E, Li L, Bodhidatta L, Sethabutr O, Triki H, Bahri O, Oderinde BS, Baba MM, Bukbuk D. Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections. J Infect Dis. 2010;201(11):163343.
- Shi T, McAllister DA, O’Brien KL, Simoes EA, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, Alassani I. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children. Lancet. 2017;390(10098):94658.
- Martin ET, Taylor J, Kuypers J, Magaret A, Wald A, Zerr D, Englund JA. Detection of bocavirus in children with respiratory symptoms may not be clinically relevant. Pediatrics. 2009;123(4):107581.
- Bao X, Liu T, Spetch L, Kolli D, Garofalo RP, Casola A. Airway epithelial cell response to human metapneumovirus infection. Virology. 2007;368(1):91101.
- Liao LL, Wu L, Zhang Z, Deng Y, Li J, Wei Q, Yang X, Ye X, Zhong N. Transcriptomic analysis of host immune responses to human metapneumovirus infection in A549 cells. Infect Genet Evol. 2016;38:12532.
- Chen AY, Cheng F, Lou S, Luo Y, Liu Z, Delwart E, Pintel D, Qiu J. Characterization of the gene expression profile of human bocavirus. Virology. 2010;403(2):14554.
- Chang A, Masante C, Buchholz UJ, Dutch RE. Human metapneumovirus (HMPV) fusion protein mediates entry via an interaction with RGDbinding integrins. J Virol. 2012;86(24):1214860.
- Okimoto T, O’Brien M, Nogales A, Hoffmann E, MartnezSobrido L. Liveattenuated vaccines for human metapneumovirus generated by codon deoptimization of the polymerase gene. Vaccines. 2020;8(1):4.
- Boeckh M, Englund JA. Evaluation and treatment of respiratory viral infections in immunocompromised patients. Expert Rev Anti Infect Ther. 2003;1(4):50516.
- Williams JV, Wang CK, Yang CF, Tollefson SJ, House FS, Heck JM, Chu Y, Brown MB, Lintao LD, Quinto JD, Hayden FG. The role of human metapneumovirus in upper respiratory tract infections in children: a 20year experience. J Infect Dis. 2006;193(3):38795.
- Blessing K, Neske F, Herre U, Kreth HW, Weissbrich B. Prolonged detection of human bocavirus DNA in respiratory samples. Eur J Pediatr. 2009;168(11):13438.
- Meissner HC, Rennels MB, Pickering LK, Hall CB. Metapneumovirus and lower respiratory tract infections in children. N Engl J Med. 2004;350(4):4435.
- Ison MG. Respiratory viral infections in transplant recipients: novel risk factors and outcomes. Curr Opin Organ Transplant. 2013;18(4):32631.
- van de Pol AC, van Loon AM, Wolfs TF, Jansen NJ, Nijhuis M, Breteler EK, Schuurman R, Rossen JW. Increased detection of respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses with realtime PCR in samples from patients with respiratory symptoms. J Clin Microbiol. 2007;45(7):22602.
- Fry AM, Curns AT, Harbor S, Hutwagner L, Holman RC, Anderson LJ. Seasonal trends of human metapneumovirus and respiratory syncytial virus detected by PCR in children. J Clin Virol. 2011;52(2):17982.
- Pozo F, GarciaGarcia ML, Calvo C, Cuesta I, Vergnano S, Casas I. High incidence of human bocavirus infection in children in Spain. J Clin Virol. 2007;40(3):2248.
- Bradford LL, Wheeler TC, Hallford G, Waner JL. Comparison of realtime PCR and conventional PCR methods for the detection of human metapneumovirus in pediatric respiratory samples. Diagn Microbiol Infect Dis. 2010;66(4):3645.
- Pabbaraju K, Tokaryk KL, Wong S, Fox JD. Comparison of the Luminex xTAG respiratory viral panel with inhouse nucleic acid extraction and realtime PCR for detection of respiratory viruses. J Clin Microbiol. 2008;46(8):305662.
- Falsey AR, Formica MA, Walsh EE. Diagnosis of human metapneumovirus infection by serology. Clin Infect Dis. 2010;50(11):e815.
- Merindol N, Pépin J, Orr P, Halle G, Fortin C, Blais R, Roy E. A novel respiratory virus panel detection assay for realtime multiplexed PCR testing of human metapneumovirus, respiratory syncytial virus A/B, and other common respiratory viruses. J Med Virol. 2018;90(2):17581.
- Kellner MJ, Koob JG, Gootenberg JS, Abudayyeh OO, Zhang F. CRISPRbased diagnostics. Nat Biotechnol. 2019;37(2):1428.
- Greninger AL, Roychoudhury P, Xie H, Casto A, Cent A, Pepper G, Huang ML, Reeves DB, Schiffer JT, Jerome KR. Ultrasensitive capture of human herpes simplex virus genomes directly from clinical samples reveals extraordinarily limited evolution in cell culture. mSphere. 2018;3(1):e0053717.
- Bastien N, Chui N, Robinson JL, Lee BE, Dust K, Hart L, Li Y. Detection of human metapneumovirus in nasopharyngeal aspirates of children with respiratory tract infections by realtime PCR. J Clin Microbiol. 2003;41(10):464850.
- Russell CJ, Hurwitz JL. Sendai virusbased human metapneumovirus vaccines: the best of both worlds? Expert Rev Vaccines. 2007;6(2):2159.
- Principi N, Esposito S. Antiviral drugs for respiratory syncytial virus infections: where are we now and what’s next? Clin Microbiol Infect. 2014;20(S6):713.
- Wyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune sera in vitro. Antivir Res. 2003;60(1):519.
- Dijkman R, Koekkoek SM, Molenkamp R, Schildgen O, van der Hoek L. Human bocavirus can mimic a polymerasedefective mutant, and the viral polymerase is critical for replication initiation. J Virol. 2009;83(10):534553.
- Kurtz JB, Lee TW, Parsons HK. The use of cidofovir in respiratory virus infections in the immunocompromised host. J Infect. 2005;50(2):1525.
- Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Black RE, Campbell H. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):140516.
References
Boivin G, De Serres G, Côte S, Gilca R, Abed Y, Rochette L, Bergeron MG, Dery P. Human metapneumovirus infections in hospitalized children. Emerg Infect Dis. 2003;9(6):63440.
van den Hoogen BG, van Doornum GJ, Fockens JC, Cornelissen JJ, Beyer WE, de Groot R, Osterhaus AD, Fouchier RA. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis. 2003;188(10):15717.
Schildgen O, Simon A, Wilkesmann A, Schildgen V, Brockmann M, Söder G, Geikowski T, Glatzel T, Kupfer B, EisHübinger AM. Human bocavirus DNA in parvovirus B19–positive patients. Emerg Infect Dis. 2008;14(8):14113.
Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, Vuorinen T, Waris M, Bjerkner A, TiveljungLindell A, van den Hoogen BG. Human bocavirus and acute wheezing in children. Clin Infect Dis. 2007;44(7):90410.
Arnold JC, Singh KK, Spector SA, Sawyer MH. Human metapneumovirus in hospitalized children. N Engl J Med. 2003;349(5):44350.
Mackay IM, Jacob KC, Woolhouse D, Waller K, Syrmis MW, Nissen MD, Sloots TP. Molecular assays for detection of human metapneumovirus. J Clin Microbiol. 2003;41(3):10014.
Bastien N, Ward D, Van Caeseele P, Brandt K, Lee SH, McNabb G, Kliewer G, Marrie TJ, Burton L, Forward K, McDonald R. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003;41(10):46426.
Calvo C, GarcíaGarcía ML, Blanco C, Pozo F, Flecha IC, PérezBreña P. Human metapneumovirus infection in children in Spain. Emerg Infect Dis. 2006;12(1):1268.
Kesebir D, Vazquez M, Weibel C, Shapiro ED, Ferguson D, Landry ML, Kahn JS. Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus. J Infect Dis. 2006;194(9):127682.
Mahony JB. Detection of respiratory viruses by molecular methods. Clin Microbiol Rev. 2008;21(4):71647.
Midulla F, Scagnolari C, Bonci E, Pierangeli A, Antonelli G, De Angelis D, Berardi R, Selvaggi C, Moretti C. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child. 2010;95(1):3541.
Kaplan NM, Dove W, AbdEldayem SA, AbuZeid AF, Shamoon HE, Hart CA. Human bocavirus infection among children, Jordan. Emerg Infect Dis. 2006;12(9):141820.
Longtin J, Bastien M, Gilca R, Leblanc E, De Serres G, Bergeron MG, Boivin G. Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis. 2008;14(2):21721.
Vicente D, Cilla G, Montes M, PérezYarza EG, PérezTrallero E. Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis. 2007;13(4):6368.
Lüef C, Frischmuth T, Weissbrich B. Detection of human bocavirus in nasopharyngeal aspirates of children and adults with respiratory tract infections. Pediatr Infect Dis J. 2005;24(8):6813.
Jin Y, Cheng W, Xu Z, Wu W, Xu M, Lu S, Jin M. High prevalence of human bocavirus 2 and its role in childhood acute gastroenteritis in China. J Clin Virol. 2011;52(3):2513.
Lu X, Chittaganpitch M, Olsen SJ, Mackay IM, Sloots TP, Fry AM, Erdman DD. Realtime PCR assays for detection of bocavirus in human specimens. J Clin Microbiol. 2006;44(9):32315.
Smuts HE, Hardie D. Human bocavirus in hospitalized children, South Africa. Emerg Infect Dis. 2006;12(9):14578.
Pilger DA, Cantarelli VV, Amantea SL, Siqueira MM, Porto NS, Takahashi GA, Barth AL. Human metapneumovirus associated with respiratory infection in southern Brazil: molecular and epidemiological features. Arch Virol. 2009;154(6):92937.
Esposito S, Zampiero A, Prada E, Montinaro V, Colombo C, Fossali E, Bosis S, Principi N. Clinical and epidemiological characteristics of children hospitalized for respiratory syncytial virus infection. J Med Virol. 2011;83(2):32430.
Biacchesi S, Skiadopoulos MH, Boivin G, Hanson CT, Murphy BR, Collins PL, Buchholz UJ. Genetic diversity between human metapneumovirus subgroups. Virology. 2003;315(1):19.
Kapoor A, Simmonds P, Slikas E, Li L, Bodhidatta L, Sethabutr O, Triki H, Bahri O, Oderinde BS, Baba MM, Bukbuk D. Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections. J Infect Dis. 2010;201(11):163343.
Shi T, McAllister DA, O’Brien KL, Simoes EA, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, Alassani I. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children. Lancet. 2017;390(10098):94658.
Martin ET, Taylor J, Kuypers J, Magaret A, Wald A, Zerr D, Englund JA. Detection of bocavirus in children with respiratory symptoms may not be clinically relevant. Pediatrics. 2009;123(4):107581.
Bao X, Liu T, Spetch L, Kolli D, Garofalo RP, Casola A. Airway epithelial cell response to human metapneumovirus infection. Virology. 2007;368(1):91101.
Liao LL, Wu L, Zhang Z, Deng Y, Li J, Wei Q, Yang X, Ye X, Zhong N. Transcriptomic analysis of host immune responses to human metapneumovirus infection in A549 cells. Infect Genet Evol. 2016;38:12532.
Chen AY, Cheng F, Lou S, Luo Y, Liu Z, Delwart E, Pintel D, Qiu J. Characterization of the gene expression profile of human bocavirus. Virology. 2010;403(2):14554.
Chang A, Masante C, Buchholz UJ, Dutch RE. Human metapneumovirus (HMPV) fusion protein mediates entry via an interaction with RGDbinding integrins. J Virol. 2012;86(24):1214860.
Okimoto T, O’Brien M, Nogales A, Hoffmann E, MartnezSobrido L. Liveattenuated vaccines for human metapneumovirus generated by codon deoptimization of the polymerase gene. Vaccines. 2020;8(1):4.
Boeckh M, Englund JA. Evaluation and treatment of respiratory viral infections in immunocompromised patients. Expert Rev Anti Infect Ther. 2003;1(4):50516.
Williams JV, Wang CK, Yang CF, Tollefson SJ, House FS, Heck JM, Chu Y, Brown MB, Lintao LD, Quinto JD, Hayden FG. The role of human metapneumovirus in upper respiratory tract infections in children: a 20year experience. J Infect Dis. 2006;193(3):38795.
Blessing K, Neske F, Herre U, Kreth HW, Weissbrich B. Prolonged detection of human bocavirus DNA in respiratory samples. Eur J Pediatr. 2009;168(11):13438.
Meissner HC, Rennels MB, Pickering LK, Hall CB. Metapneumovirus and lower respiratory tract infections in children. N Engl J Med. 2004;350(4):4435.
Ison MG. Respiratory viral infections in transplant recipients: novel risk factors and outcomes. Curr Opin Organ Transplant. 2013;18(4):32631.
van de Pol AC, van Loon AM, Wolfs TF, Jansen NJ, Nijhuis M, Breteler EK, Schuurman R, Rossen JW. Increased detection of respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses with realtime PCR in samples from patients with respiratory symptoms. J Clin Microbiol. 2007;45(7):22602.
Fry AM, Curns AT, Harbor S, Hutwagner L, Holman RC, Anderson LJ. Seasonal trends of human metapneumovirus and respiratory syncytial virus detected by PCR in children. J Clin Virol. 2011;52(2):17982.
Pozo F, GarciaGarcia ML, Calvo C, Cuesta I, Vergnano S, Casas I. High incidence of human bocavirus infection in children in Spain. J Clin Virol. 2007;40(3):2248.
Bradford LL, Wheeler TC, Hallford G, Waner JL. Comparison of realtime PCR and conventional PCR methods for the detection of human metapneumovirus in pediatric respiratory samples. Diagn Microbiol Infect Dis. 2010;66(4):3645.
Pabbaraju K, Tokaryk KL, Wong S, Fox JD. Comparison of the Luminex xTAG respiratory viral panel with inhouse nucleic acid extraction and realtime PCR for detection of respiratory viruses. J Clin Microbiol. 2008;46(8):305662.
Falsey AR, Formica MA, Walsh EE. Diagnosis of human metapneumovirus infection by serology. Clin Infect Dis. 2010;50(11):e815.
Merindol N, Pépin J, Orr P, Halle G, Fortin C, Blais R, Roy E. A novel respiratory virus panel detection assay for realtime multiplexed PCR testing of human metapneumovirus, respiratory syncytial virus A/B, and other common respiratory viruses. J Med Virol. 2018;90(2):17581.
Kellner MJ, Koob JG, Gootenberg JS, Abudayyeh OO, Zhang F. CRISPRbased diagnostics. Nat Biotechnol. 2019;37(2):1428.
Greninger AL, Roychoudhury P, Xie H, Casto A, Cent A, Pepper G, Huang ML, Reeves DB, Schiffer JT, Jerome KR. Ultrasensitive capture of human herpes simplex virus genomes directly from clinical samples reveals extraordinarily limited evolution in cell culture. mSphere. 2018;3(1):e0053717.
Bastien N, Chui N, Robinson JL, Lee BE, Dust K, Hart L, Li Y. Detection of human metapneumovirus in nasopharyngeal aspirates of children with respiratory tract infections by realtime PCR. J Clin Microbiol. 2003;41(10):464850.
Russell CJ, Hurwitz JL. Sendai virusbased human metapneumovirus vaccines: the best of both worlds? Expert Rev Vaccines. 2007;6(2):2159.
Principi N, Esposito S. Antiviral drugs for respiratory syncytial virus infections: where are we now and what’s next? Clin Microbiol Infect. 2014;20(S6):713.
Wyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune sera in vitro. Antivir Res. 2003;60(1):519.
Dijkman R, Koekkoek SM, Molenkamp R, Schildgen O, van der Hoek L. Human bocavirus can mimic a polymerasedefective mutant, and the viral polymerase is critical for replication initiation. J Virol. 2009;83(10):534553.
Kurtz JB, Lee TW, Parsons HK. The use of cidofovir in respiratory virus infections in the immunocompromised host. J Infect. 2005;50(2):1525.
Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Black RE, Campbell H. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):140516.