İnsan parechoviruslarının özellikleri, epidemiyolojisi ve klinik önemi

Yıl 2019, Cilt: 44 Sayı: 3, 1118 - 1130, 30.09.2019

Semih Tokak , Mehmet Özdemir

https://doi.org/10.17826/cumj.528673

Öz

İnsan Parechoviruslar (Human Parechovirus; HPeV) tek iplikli, pozitif polariteli RNA viruslarıdır.  Başlangıçta klinik ve morfolojik özelliklerine göre insan enterovirusları içerisinde Echovirus 22 ve 23 olarak tanımlansalar da, genom organizasyonu, yapı ve replikasyonlarında birkaç farklı özellikleriyle enteroviruslar ve diğer picornavirus gruplarından farklı oldukları gösterilmiştir. HPeV’ler genetik ve antijenik heterojenlik göstermekte ve birçok tipi dünyanın her yerinde bulunan insan popülasyonunda yaygın bir şekilde bulunmaktadır. HPeV1 en yaygın genotip olup sıklıkla gastrointestinal ve solunum yolu hastalıklarına neden olmaktadır. HPeV3 enfeksiyonu yenidoğanlarda ve 3 aydan daha küçük infantlarda sepsis, meningoensefalit, nörolojik sekellere ve ölümlere yol açmaktadır. Küçük infantlarda tipik klinik tablo, ateş, şiddetli sinirlilik ve kızarıklıktan oluşur ve sıklıkla “ateşli, kırmızı döküntülü, kızgın bebekler” tanımına sebep olmaktadır. Günümüzde HPeV’lerin tanısı için en duyarlı metod real-time polimeraz zincir reaksiyonudur. Enfeksiyonlarının tedavisinde şimdiye kadar kadar herhangi bir spesifik antiviral tedavi mevcut olmayıp monoklonal antikorların kullanımı değerlendirilmektedir.  HPeV’ler üzerine yapılacak daha fazla çalışma ile bu virusların spesifik karakteristiklerinin anlaşılmasına ve uygun tedavi stratejilerinin geliştirilmesine ihtiyaç vardır.

Anahtar Kelimeler

HPeV tipleri, Klinik özellikler, Tanı, Epidemiyoloji

Characteristics, epidemiology and clinical importance of human parechoviruses

Öz

Human parechoviruses (HPeVs) are single-stranded, positive-sense RNA viruses. Although originally described as echovirus 22 and 23 within human enteroviruses because of their clinical and morphological properties, they have since been shown to be distinct from this and other picornavirus groups in several features of their genome organisation, structure and replication. HPeVs show genetic and antigenic heterogeneity and a number of distinct types are known to circulate widely in human populations throughout the world. HPeV1 causes mostly gastrointestinal and respiratory tract infections. HPeV3 can cause sepsis and meningoencephalitis in neonates and infants younger than 3 months, which could lead to neurological sequelae and death. In young infants, the typical clinical presentation includes fever, severe irritability, and rash, often leading to descriptions of “hot, red, angry babies”. Nowadays, the most sensitive method for detecting HPeV is real-time polymerase chain reaction assays. In the treatment of infections, no specific antiviral therapy has been available so far and the use of monoclonal antibodies is still being evaluated. More research is therefore needed to understand the specific characteristics of this viruses and to develop appropriate treatment strategies.

Anahtar Kelimeler

HPeV types, Clinical charecteristics, Diagnosis, Epidemiology

Kaynakça

• 1. Lauber C, Gorbalenya AE. Partitioning the genetic diversity of a virus family: approach and evaluation through a case study of picornaviruses. J Virol. 2012; 86(7):3890-904.
• 2. Picornaviridae.com, http://www.picornaviridae.com/(Erişimi tarihi:06.02.2018)
• 3. Racaniello Vincent R. Picornaviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields virology. 6th ed., vol. 1. Philadelphia: Lippincott Williams and Wilkins; 2013. p. 610.
• 4. Hyypiä T, Horsnell C, Maaronen M, Khan M, Kalkkinen N, Auvinen P. et al. A distinct picornavirus group identified by sequence analysis. Proc Natl Acad Sci USA. 1992; 89(18): 8847-51.
• 5. Cristanziano VD, Bottcher S, Diedrich S, Timmen-Wego M, Knops E, Lubke N, et al. Detection and characterization of enteroviruses and parechoviruses in healthy people living in the South of Cote d'Ivoire. J Clin Virol. 2015; 71(1): 40-3.
• 6. Chuchaona W, Khamrin P, Yodmeeklin A, Saikruang W, Kongsricharoern T, Ukarapol N, et al. Detection and characterization of a novel human parechovirus genotype in Thailand. Infect Genet Evol. 2015; 31(1): 300-4.
• 7. Nateri AS, Hughes PJ, Stanway G. In vivo and in vitro identification of structural and sequence elements of the human parechovirus 5' untranslated region required for internal initiation. J Virol. 2000; 74(14): 6269-77.
• 8. Nateri AS, Hughes PJ, Stanway G. Terminal RNA replication elements in human parechovirus 1. J Virol. 2002; 76(24): 13116-22.
• 9. Stanway G, Kalkkinen N, Roivainen M, Ghazi F, Khan M, Smyth M, Meurman O, Hyypiä T. Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group. J Virol. 1994; 68(12): 8232-8.
• 10. Harvala H, Simmonds P. Human parechoviruses: biology, epidemiology and clinical significance. J Clin Virol. 2009; 45(1): 1-9.
• 11. Wildenbeest JG, Harvala H, Pajkrt D, Wolthers KC. The need for treatment against human parechoviruses: how, why and when? Expert Rev Anti Infect Ther. 2010; 8(12): 1417-29.
• 12. Schultheiss T, Emerson SU, Purcell RH, Gauss-Muller V. Polyprotein processing in echovirus 22: a first assessment. Biochem Biophys Res Commun. 1995. 26; 217(1): 1120–7.
• 13. Krogerus C, Samuilova O, Poyry T, Jokitalo E, Hyypia T. Intracellular localization and effects of individually expressed human parechovirus 1 non-structural proteins. J Gen Virol. 2007. 88(Pt 3): 831–41.
• 14. Simmonds P, Welch J. Frequency and dynamics of recombination within different species of human enteroviruses. J Virol. 2006; 80(1): 483–93.
• 15. Simmonds P. 2006. Recombination and selection in the evolution of picornaviruses and other Mammalian positive-stranded RNA viruses. J Virol. 80: 11124–40.
• 16. Benschop KS, Williams CH, Wolthers KC, Stanway G, Simmonds P. Widespread recombination within human parechoviruses: analysis of temporal dynamics and constraints. J Gen Virol. 2008; 89(Pt 4): 1030–5.
• 17. Benschop KS, de VM, Minnaar RP, Stanway G, van der Hoek L, Wolthers KC, Simmonds P. Comprehensive full-length sequence analyses of human parechoviruses: diversity and recombination. J Gen Virol. 2010(Pt 1); 91: 145–54.
• 18. Swiss Institute of Bioinformatics. 2011. ViralZone. Swiss Institute of Bioinformatics, Lausanne, Switzerland. http://www.expasy.org/viralzone.
• 19. Faria NR, de Vries M, van Hemert FJ, Benschop K, van der Hoek L. Rooting human parechovirus evolution in time. BMC Evol Biol. 2009; 15;9: 164.
• 20. Drake JW, Holland JJ. Mutation rates among RNA viruses. Proc Natl Acad Sci USA. 1999; 23; 96(24): 13910-3.
• 21. Sun GM, Wang Y, Tao G, Shen Q, Cao WP, Chang XL, et al. Complete Genome Sequence of a Novel Type of Human Parechovirus Strain Reveals Natural Recombination Events. J Virol. 2012. 86(16): 8892-3.
• 22. Baumgarte S, de Souza Luna LK, Grywna K, Panning M, Drexler JF, Karsten C, et al. Prevalence, types, and RNA concentrations of human parechoviruses, including a sixth parechovirus type, in stool samples from patients with acute enteritis. J Clin Microbiol 2008. 46(1): 242-8.
• 23. Zuckerman AJ, Banatvala JE, Pattison JR. Picornaviridae. In: Principles and Practice of Clinical Virology, 4th ed.,1999:23.
• 24. Oberste MS, Feeroz MM, Maher K, Nix WA, Engel GA, Begum S, et al. Naturally acquired picornavirus infections in primates at the Dhaka zoo. J Virol. 2013; 87(1): 572-80.
• 25. Oberste MS, Feeroz MM, Maher K, Nix WA, Engel GA, Hasan KM, et al. Characterizing the picornavirus landscape among synanthropic nonhuman primates in Bangladesh, 2007 to 2008. J Virol. 2013;87(1):558-71.
• 26. Ito M, Yamashita T, Tsuzuki H, Takeda N, Sakae K. Isolation and identification of a novel human parechovirus. J Gen Virol. 2004; 85(Pt 2): 391-8.
• 27. Boivin G, Abed Y, Boucher FD. Human parechovirus 3 and neonatal infections. Emerg Infect Dis 2005; 11(1):103-5.
• 28. Benschop KS, Schinkel J, Minnaar RP, Pajkrt D, Spanjerberg L, Kraakman HC, et al. Human parechovirus infections in Dutch children and the association between serotype and disease severity. Clin Infect Dis. 2006;42(2):204-10.
• 29. Schnurr D, Dondero M, Holland D, Connor J. Characterization of echovirus 22 variants. Arch Virol. 1996; 141(9): 1749-58.
• 30. Al-Sunaidi M, Williams CH, Hughes PJ, Schnurr DP, Stanway G. Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains. J Virol. 2007; 81(2): 1013-21.
• 31. Oberste MS, Maher K, Pallansch MA. Complete sequence of echovirus 23 and its relationship to echovirus 22 and other human enteroviruses. Virus Res. 1998; 56(2): 217-23.
• 32. Watanabe K, Oie M, Higuchi M, Nishikawa M, Fujii M. Isolation and characterization of novel human parechovirus from clinical samples. Emerg Infect Dis. 2007; 13(6): 889-95.
• 33. Li L, Victoria J, Kapoor A, Naeem A, Shaukat S, Sharif S, et al. Genomic characterization of novel human parechovirus type. Emerg Infect Dis. 2009; 15(2): 288-91.
• 34. Drexler JF, Grywna K, Stöcker A, Almeida PS, Medrado-Ribeiro TC, Eschbach-Bludau M, et al. Novel human parechovirus from Brazil. Emerg Infect Dis. 2009; 15(2): 310-3.
• 35. Pham NT, Chan-It W, Khamrin P, Nishimura S, Kikuta H, Sugita K, et al. Detection of human parechovirus in stool samples collected from children with acute gastroenteritis in Japan during 2007-2008. J Med Virol. 2011; 83(2): 331-6.
• 36. Benschop K, Thomas X, Serpenti C, Molenkamp R, Wolthers K. High prevalence of human Parechovirus (HPeV) genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. J Clin Microbiol. 2008; 46(12): 3965-70.
• 37. Calvert J, Chieochansin T, Benschop K, McWilliam Leitch EC, Drexler JF, Grywna K, The recombination Dynamics of human parechoviruses; investigation of type-specific differences in frequency and epidemiological correlates. J Gen Virol. 2010; 91(Pt 5): 1229-38.
• 38. Böttcher S, Obermeier PE, Diedrich S, Kaboré Y, D'Alfonso R, Pfister H, et al. Genome Sequence of Novel Human Parechovirus Type 17. Genome Announc. 2017; 23; 5(8).
• 39. Shan TL, Wang CM, Cui L, Delwart E, Yuan CL, Zhao W, et al. Human Parechovirus Infections in Monkeys with Diarrhea, China. Emerg Infect Dis. 2010. 16(7): 1168-9.
• 40. Wigand R, Sabın Ab. Properties of ECHO types 22, 23 and 24 viruses. Arch Gesamte Virusforsch. 1961; 11: 224-47.
• 41. Nix WA, Khetsuriani N, Peñaranda S, Maher K, Venczel L, Cselkó Z, et al. Diversity of picornaviruses in rural Bolivia. J Gen Virol. 2013;94(Pt 9):2017-28.
• 42. Kim Pham NT, Trinh QD, Takanashi S, Abeysekera C, Abeygunawardene A, Shimizu H, et al. Novel human parechovirus, Sri Lanka. Emerg Infect Dis. 2010; 16(1): 130-2.
• 43. Pham NT, Takanashi S, Tran DN, Trinh QD, Abeysekera C, Abeygunawardene A, et al. Human parechovirus infection in children hospitalized with acute gastroenteritis in Sri Lanka. J Clin Microbiol. 2011; 49(1): 364-6.
• 44. Benschop K, Thomas X, Serpenti C, Molenkamp R, Wolthers K. High prevalence of human Parechovirus (HPeV) genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. J Clin Microbiol. 2008; 46(12): 3965-70.
• 45. Joki-Korpela P, Hyypiä T. Parechoviruses, a novel group of human picornaviruses. Ann Med. 2001; 33(7): 466-71.
• 46. Harvala H, Wolthers KC, Simmonds P. Parechoviruses in children: understanding a new infection. Curr Opin Infect Dis. 2010; 23(3): 224-30.
• 47. Grist NR, Bell EJ, Assaad F. Enteroviruses in human disease. Progress in medical virology. Fortschritte der medizinischen Virusforschung Progres en virologie medicale. 1978; 24:114-57.
• 48. Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA; Centers for Disease Control and Prevention. Enterovirus surveillance--United States, 1970-2005. MMWR Surveill Summ. 2006; 55(8): 1-20.
• 49. Ehrnst A, Eriksson M. Echovirus type 23 observed as a nosocomial infection in infants. Scand J Infect Dis 1996; 28(2): 205-6.
• 50. Tauriainen S, Martiskainen M, Oikarinen S, Lönnrot M, Viskari H, Ilonen J. Human parechovirus 1 infections in young children--no association with type 1 diabetes. J Med Virol 2007; 79(4): 457-62.
• 51. Kolehmainen P, Oikarinen S, Koskiniemi M, Simell O, Ilonen J, Knip M, et al. Human parechoviruses are frequently detected in stool of healthy Finnish chil-dren. J Clin Virol. 2012; 54: 156–61.
• 52. Abed Y, Boivin G. Human parechovirus types 1, 2 and 3 infections in Canada. Emerg Infect Dis. 2006; 12(6): 969-75.
• 53. Verboon-Maciolek MA, Groenendaal F, Hahn CD, Hellmann J, van Loon AM, Boivin G, et al. 2008. Human parechovirus causes encephalitis with white matter injury in neonates. Ann Neurol. 64(3):266-273.
• 54. Piñeiro L, Vicente D, Montes M, Hernández-Dorronsoro U, Cilla G. Human parechoviruses in infants with systemic infection. J Med Virol. 2010; 82(10): 1790-6.
• 55. Shoji K, Komuro H, Miyata I, Miyairi I, Saitoh A. Dermatologic manifestations of human parechovirus type 3 infection in neonates and infants. Pediatr Infect Dis J. 2013; 32(3): 233-6.
• 56. Pajkrt D, Benschop KS, Westerhuis B, Molenkamp R, Spanjerberg L, Wolthers KC. Clinical characteristics of human parechoviruses 4-6 infections in young children. Pediatr Infect Dis J. 2009; 28(11): 1008-10.
• 57. Figueroa JP, Ashley D, King D, Hull B. An outbreak of acute flaccid paralysis in Jamaica associated with echovirus type 22. J Med Virol. 1989; 29(4): 315-9.
• 58. Koskiniemi M, Paetau R, Linnavuori K. Severe encephalitis associated with disseminated echovirus 22 infection. Scand J Infect Dis. 1989; 21(4): 463-6.
• 59. Legay V, Chomel JJ, Fernandez E, Lina B, Aymard M, Khalfan S. Encephalomyelitis due to human parechovirus type 1. J Clin Virol. 2002; 25(2): 193-5.
• 60. Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Bergevoet RM, Spijkerman IJ, et al. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis. 2008; 1;47(3): 358-63.
• 61. Benschop KS, Schinkel J, Minnaar RP, Pajkrt D, Spanjerberg L, Kraakman HC, et al. Human parechovirus infections in Dutch children and the association between serotype and disease severity. Clin Infect Dis. 2006. 42:204–10.
• 62. Boivin G, Abed Y, Boucher FD. Human parechovirus 3 and neonatal infections. Emerg Infect Dis. 2005; 11: 103–5.
• 63. Levorson RE, Jantausch BA, Wiedermann BL, Spiegel HM, Campos JM. Human Parechovirus -3 infection: emerging pathogen in neonatal sepsis 2. Pediatr Infect Dis J. 2009; 28(1): 545–47.
• 64. Eis-Hübinger A, Eckerle I, Helmer A, Reber U, Dresbach T, Buderus S. et al. Two cases of sepsis-like illness in infants caused by human parechovirus traced back to elder siblings with mild gastroenteritis and respiratory symptoms. J Clin Microbiol. 2013; 51:715–8.
• 65. Renna S, Bergamino L, Pirlo D, Rossi A, Furione M, Piralla A. et al. A case of neonatal human parechovirus encephalitis with a favourable outcome. Brain Dev. 2014; 36(1): 70-3.
• 66. Harvala H, McLeish N, Kondracka J, McIntyre CL, McWilliam Leitch EC, Templeton K. et al. Comparison of human parechovirus and enterovirus detection frequencies in cerebrospinal fluid samples collected over a 5-year period in edinburgh: HPeV type 3 identified as the most common picornavirus type. J Med Virol. 2011; 83(5): 889-96.
• 67. Ito M, Yamashita T, Tsuzuki H, Kabashima Y, Hasegawa A, Nagaya S, et al. Detection of human parechoviruses from clinical stool samples in Aichi, Japan. J Clin Microbiol 2010; 48(8): 2683-8.
• 68. Wolthers K, Benschop K, Schinkell J, Motenkamp R, Spijkerman I, Kraakman H, et al. Human parechoviruses (HPeV) as an important cause for sepsis/meningitis in infants. Acta Clin Belg. 2007. 62(6): 452-452.
• 69. Cumming G, Khatami A, McMullan BJ, Musto J, Leung K, Nguyen O, et al. Parechovirus genotype 3 outbreak among infants, New South Wales, Australia, 2013-2014. Emerg Infect Dis. 2015; 21: 1144-52.
• 70. Felsenstein S, Yang S, Eubanks N, Sobrera E, Grimm JP, Aldrovandi G. Human parechovirus central nervous system infections in southern California children. Pediatr Infect Dis J. 2014; 33(4): e87-91.
• 71. Renaud C, Kuypers J, Ficken E, Cent A, Corey L, Englund JA. Introduction of a novel parechovirus RT-PCR clinical test in a regional medical center. J Clin Virol. 2011; 51(1): 50-3.
• 72. Sharp J, Harrison CJ, Puckett K, Selvaraju SB, Penaranda S, Nix WA, et al. Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal fluid during sepsis evaluations. Pediatr Infect Dis J. 2013;32(3):213-6.
• 73. Ljubin-Sternak S, Juretić E, Šantak M, Pleša M, Forčić D, Vilibić-Čavlek T, et al. Clinical and molecular characterization of a parechovirus type 1 outbreak in neonates in Croatia. J Med Virol. 2011; 83(1):137-41.
• 74. Sedmak G, Nix WA, Jentzen J, Haupt TE, Davis JP, Bhattacharyya S, et al. Infant deaths associated with human parechovirus infection in Wisconsin. Clin Infect Dis. 2010; 50(3): 357- 61.
• 75. Fischer TK, Midgley S, Dalgaard C, Nielsen AY. Human Parechovirus Infection, Denmark. Emerg Infect Dis. 2014. 20(1): 83-7.
• 76. Schuffenecker I, Javouhey E, Gillet Y, Kugener B, Billaud G, Floret D, et al. Human parechovirus infections, Lyon, France, 2008-10: evidence for severe cases. J Clin Virol. 2012; 54(4): 337-41.
• 77. van Zwol AL, Lequin M, Aarts-Tesselaar C, van der Eijk AA, Driessen GA, de Hoog M, et al. Fatal neonatal parechovirus encephalitis. BMJ Case Rep.2009;2009.
• 78. Sharp J, Bell J, Harrison CJ, Nix WA, Oberste MS, Selvarangan R. Human parechovirus in respiratory specimens from children in Kansas City, Missouri. J Clin Microbiol. 2012; 50(12): 4111-3.
• 79. Esposito S, Rahamat-Langendoen J, Ascolese B, Senatore L, Castellazzi L, Niesters HG. Pediatric parechovirus infections. J Clin Virol. 2014; 60(2): 84-9.
• 80. http://www.picornastudygroup.com/(Erişimi tarihi:03.04.2018)
• 81. Pulli T, Koivunen E, Hyypiä T. Cell-surface interactions of echovirus 22. J Biol Chem. 1997; 272(34): 21176-80.
• 82. Triantafilou K, Triantafilou M, Takada Y, Fernandez N. Human parechovirus 1 utilizes integrins alphavbeta3 and alphavbeta1 as receptors. J Virol. 2000; 74(13): 5856-62.
• 83. Seitsonen J, Susi P, Heikkilä O, Sinkovits RS, Laurinmäki P, Hyypiä T, et al. Interaction of alphaVbeta3 and alphaVbeta6 integrins with human parechovirus 1. J Virol. 2010; 84(17): 8509-19.
• 84. Triantafilou K, Vakakis E, Orthopoulos G, Ahmed MA, Schumann C, Lepper PM, et al. TLR8 and TLR7 are involved in the host’s immune response to humanparechovirus 1. Eur J Immunol. 2005; 35(8): 2416–23.
• 85. Westerhuis BM, Koen G, Wildenbeest JG, Pajkrt D, de Jong MD, Benschop KS, et al.: Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and therapy development. J Gen Virol. 2012, 93: 2363-70.
• 86. Volpe JJ. Neonatal encephalitis and white matter injury: more than just inflam-mation. Ann Neurol 2008; 64: 232–6.
• 87. Nix WA, Maher K, Johansson ES, Niklasson B, Lindberg AM, Pallansch MA, et al. Detection of all known parechoviruses by real-time PCR. J Clin Microbiol. 2008;46(8):2519-2524.
• 88. Abzug MJ, Keyserling HL, Lee ML, Levin MJ, Rotbart HA. Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin. Clin Infect Dis. 1995; 20(5): 1201-6.
• 89. de Crom SC, Obihara CC, de Moor RA, Veldkamp EJ, van Furth AM, Rossen JW. Prospective comparison of the detection rates of human enterovirus and parechovirus RT-qPCR and viral culture in different pediatric specimens. J Clin Virol. 2013; 58(2): 449-54.
• 90. Khatami A, McMullan BJ, Webber M, Stewart P, Francis S, Timmers KJ, et al. Sepsis-like disease in infants due to human parechovirus type 3 during an outbreak in Australia. Clin Infect Dis. 2015; 60(2): 228-36.
• 91. Li C, Wang H, Shih SR, Chen TC, Li ML. The efficacy of viral capsid inhibitorsin human enterovirus infection and associated diseases. Curr Med Chem. 2007; 14(8): 847–56.
• 92. Aizawa Y, Watanabe K, Oishi T, Hirano H, Hasegawa I, Saitoh A. Role of maternal antibodies in infants with severe diseases related to human parechovirus type 3. Emerg Infect Dis. 2015; 21(1): 1966-72.
• 93. Izumita R, Aizawa Y, Watanabe K, Saitoh A. A role of intravenous immunoglobulin in human parechovirus type 3 infection in an in vitro model. Open Forum Infect Dis. 2016; 3(1): 152.