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Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children

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Abstract

Human cytomegalovirus (CMV) is the leading cause of intrauterine viral infection. The association of genetic polymorphisms in some particular genes with the incidence and severity of congenital infection has been controversial. To address this issue, we analyzed the genotypes of the glycoprotein B (gB), UL144 and UL149 genes of CMV clinical strains obtained from 33 congenitally and 31 postnatally infected Japanese children. Our results demonstrated that (1) CMV strains with any combination of genotypes could be vertically transmitted from mother to fetus, potentially causing neurological abnormalities, (2) the gB3 genotype was more prevalent in the congenital cases than in postnatally infected children (P < 0.05), particularly in congenital cases with sensorineural hearing loss (P = 0.009), (3) there was no relationship between gB genotype and viral load in the urine and dried umbilical cord specimens in the congenital cases, and (4) the UL144 and UL149 genotype distributions had no bias for congenial infection. In future studies, it would be interesting to see whether the gB genotypes serve as a prognostic indicator of CMV-associated diseases.

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Abbreviations

CMV:

Cytomegalovirus

PCR:

Polymerase chain reaction

SNHL:

Sensorineural hearing loss

References

  1. Aquino VH, Figueiredo LT (2000) High prevalence of renal transplant recipients infected with more than one cytomegalovirus glycoprotein B genotype. J Med Virol 61(1):138–142

    Article  PubMed  CAS  Google Scholar 

  2. Arav-Boger R, Battaglia CA, Lazzarotto T, Gabrielli L, Zong JC, Hayward GS, Diener-West M, Landini MP (2006) Cytomegalovirus (CMV)-encoded UL144 (truncated tumor necrosis factor receptor) and outcome of congenital CMV infection. J Infect Dis 194(4):464–473

    Article  PubMed  Google Scholar 

  3. Arav-Boger R, Foster CB, Zong JC, Pass RF (2006) Human cytomegalovirus-encoded alpha -chemokines exhibit high sequence variability in congenitally infected newborns. J Infect Dis 193(6):788–791

    Article  PubMed  CAS  Google Scholar 

  4. Arav-Boger R, Willoughby RE, Pass RF, Zong JC, Jang WJ, Alcendor D, Hayward GS (2002) Polymorphisms of the cytomegalovirus (CMV)-encoded tumor necrosis factor-alpha and beta-chemokine receptors in congenital CMV disease. J Infect Dis 186(8):1057–1064

    Article  PubMed  CAS  Google Scholar 

  5. Bale JF Jr, Murph JR, Demmler GJ, Dawson J, Miller JE, Petheram SJ (2000) Intrauterine cytomegalovirus infection and glycoprotein B genotypes. J Infect Dis 182(3):933–936

    Article  PubMed  CAS  Google Scholar 

  6. Bale JF Jr, Petheram SJ, Robertson M, Murph JR, Demmler G (2001) Human cytomegalovirus a sequence and UL144 variability in strains from infected children. J Med Virol 65(1):90–96

    Article  PubMed  CAS  Google Scholar 

  7. Barbi M, Binda S, Caroppo S, Primache V, Dido P, Guidotti P, Corbetta C, Melotti D (2001) CMV gB genotypes and outcome of vertical transmission: study on dried blood spots of congenitally infected babies. J Clin Virol 21(1):75–79

    Article  PubMed  CAS  Google Scholar 

  8. Bongarts A, Von Laer D, Vogelberg C, Ebert K, Van Lunzen J, Garweg J, Vaith P, Hufert FT, Haller O, Meyer-Konig U (1996) Glycoprotein B genotype of human cytomegalovirus: distribution in HIV-infected patients. Scand J Infect Dis 28(5):447–449

    Article  PubMed  CAS  Google Scholar 

  9. Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, Britt WJ (2005) Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 146(6):817–823

    Article  PubMed  Google Scholar 

  10. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ (2001) Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med 344(18):1366–1371

    Article  PubMed  CAS  Google Scholar 

  11. Chou SW (1992) Comparative analysis of sequence variation in gp116 and gp55 components of glycoprotein B of human cytomegalovirus. Virology 188(1):388–390

    Article  PubMed  CAS  Google Scholar 

  12. Chou SW, Dennison KM (1991) Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. J Infect Dis 163(6):1229–1234

    PubMed  CAS  Google Scholar 

  13. Coaquette A, Bourgeois A, Dirand C, Varin A, Chen W, Herbein G (2004) Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin Infect Dis 39(2):155–161

    Article  PubMed  Google Scholar 

  14. Dolan A, Cunningham C, Hector RD, Hassan-Walker AF, Lee L, Addison C, Dargan DJ, McGeoch DJ, Gatherer D, Emery VC, Griffiths PD, Sinzger C, McSharry BP, Wilkinson GW, Davison AJ (2004) Genetic content of wild-type human cytomegalovirus. J Gen Virol 85(Pt 5):1301–1312

    Article  PubMed  CAS  Google Scholar 

  15. Fries BC, Chou S, Boeckh M, Torok-Storb B (1994) Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone marrow transplant recipients. J Infect Dis 169(4):769–774

    PubMed  CAS  Google Scholar 

  16. Gaytant MA, Steegers EA, Semmekrot BA, Merkus HM, Galama JM (2002) Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv 57(4):245–256

    Article  PubMed  Google Scholar 

  17. Hahn G, Revello MG, Patrone M, Percivalle E, Campanini G, Sarasini A, Wagner M, Gallina A, Milanesi G, Koszinowski U, Baldanti F, Gerna G (2004) Human cytomegalovirus UL131–128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78(18):10023–10033

    Article  PubMed  CAS  Google Scholar 

  18. Humar A, Kumar D, Gilbert C, Boivin G (2003) Cytomegalovirus (CMV) glycoprotein B genotypes and response to antiviral therapy, in solid-organ-transplant recipients with CMV disease. J Infect Dis 188(4):581–584

    Article  PubMed  CAS  Google Scholar 

  19. Inoue N, Koyano S (2008) Evaluation of screening tests for congenital cytomegalovirus infection. Ped Infec Dis J 27(2):182–184

    Google Scholar 

  20. Ishibashi K, Tokumoto T, Tanabe K, Shirakawa H, Hashimoto K, Kushida N, Yanagida T, Inoue N, Yamaguchi O, Toma H, Suzutani T (2007) Association of the outcome of renal transplantation with antibody response to cytomegalovirus strain-specific glycoprotein H epitopes. Clin Infect Dis 45(1):60–67

    Article  PubMed  CAS  Google Scholar 

  21. Ji YH, Ruan Q, Sun ZR, Ma YP, He R, Qi Y, Huang YJ (2006) Structure and variability of the UL149 open reading frame from low-passage clinical isolates of human cytomegalovirus. J Virol Methods 131(1):72–77

    Article  PubMed  CAS  Google Scholar 

  22. Jin H, Wang X, Li S (2007) Human cytomegalovirus glycoprotein B genotype correlates with different symptoms of infected infants. Intervirology 50(3):219–223

    Article  PubMed  Google Scholar 

  23. Koyano S, Araki A, Hirano Y, Fujieda K, Suzutani T, Yagyu K, Murono K, Inoue N (2004) Retrospective diagnosis of congenital cytomegalovirus infection using dried umbilical cords. Pediatr Infect Dis J 23(5):481–482

    Article  PubMed  Google Scholar 

  24. Kumar S, Tamura K, Nei M (2004) MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5(2):150–163

    Article  PubMed  CAS  Google Scholar 

  25. Lurain NS, Kapell KS, Huang DD, Short JA, Paintsil J, Winkfield E, Benedict CA, Ware CF, Bremer JW (1999) Human cytomegalovirus UL144 open reading frame: sequence hypervariability in low-passage clinical isolates. J Virol 73(12):10040–10050

    PubMed  CAS  Google Scholar 

  26. Mao ZQ, He R, Sun M, Qi Y, Huang YJ, Ruan Q (2007) The relationship between polymorphisms of HCMV UL144 ORF and clinical manifestations in 73 strains with congenital and/or perinatal HCMV infection. Arch Virol 152(1):115–124

    Article  PubMed  CAS  Google Scholar 

  27. Mattick C, Dewin D, Polley S, Sevilla-Reyes E, Pignatelli S, Rawlinson W, Wilkinson G, Dal Monte P, Gompels UA (2004) Linkage of human cytomegalovirus glycoprotein gO variant groups identified from worldwide clinical isolates with gN genotypes, implications for disease associations and evidence for N-terminal sites of positive selection. Virology 318(2):582–597

    Article  PubMed  CAS  Google Scholar 

  28. Meyer-König U, Vogelberg C, Bongarts A, Kampa D, Delbruck R, Wolff-Vorbeck G, Kirste G, Haberland M, Hufert FT, von Laer D (1998) Glycoprotein B genotype correlates with cell tropism in vivo of human cytomegalovirus infection. J Med Virol 55(1):75–81

    Article  PubMed  Google Scholar 

  29. Murayama T, Takegoshi M, Tanuma J, Eizuru Y (2005) Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan. Intervirology 48(2–3):201–206

    Article  PubMed  CAS  Google Scholar 

  30. Ogawa H, Baba Y, Suzutani T, Inoue N, Fukushima E, Omori K (2006) Congenital cytomegalovirus infection diagnosed by polymerase chain reaction with the use of preserved umbilical cord in sensorineural hearing loss children. Laryngoscope 116(11):1991–1994

    Article  PubMed  Google Scholar 

  31. Ogawa H, Suzutani T, Baba Y, Koyano S, Nozawa N, Ishibashi K, Fujieda K, Inoue N, Omori K (2007) Etiology of severe sensorineural hearing loss in children: independent impact of congenital cytomegalovirus infection and GJB2 mutations. J Infect Dis 195(6):782–788

    Article  PubMed  CAS  Google Scholar 

  32. Pass RF (2001) Cytomegalovirus. In: Knipe DM, Howley PM (eds) Fields virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2675–2705

    Google Scholar 

  33. Peek R, Verbraak F, Bruinenberg M, Van der LA, Van den HG, Kijlstra A (1998) Cytomegalovirus glycoprotein B genotyping in ocular fluids and blood of AIDS patients with cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 39(7):1183–1187

    PubMed  CAS  Google Scholar 

  34. Picone O, Costa JM, Chaix ML, Ville Y, Rouzioux C, Leruez-Ville M (2005) Human cytomegalovirus UL144 gene polymorphisms in congenital infections. J Clin Microbiol 43(1):25–29

    Article  PubMed  CAS  Google Scholar 

  35. Picone O, Costa JM, Leruez-Ville M, Ernault P, Olivi M, Ville Y (2004) Cytomegalovirus (CMV) glycoprotein B genotype and CMV DNA load in the amniotic fluid of infected fetuses. Prenat Diagn 24(12):1001–1006

    Article  PubMed  CAS  Google Scholar 

  36. Pignatelli S, Dal Monte P, Rossini G, Lazzarotto T, Gatto MR, Landini MP (2003) Intrauterine cytomegalovirus infection and glycoprotein N (gN) genotypes. J Clin Virol 28(1):38–43

    Article  PubMed  CAS  Google Scholar 

  37. Pignatelli S, Dal Monte P, Rossini G, Landini MP (2004) Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol 14(6):383–410

    Article  PubMed  CAS  Google Scholar 

  38. Prichard MN, Penfold ME, Duke GM, Spaete RR, Kemble GW (2001) A review of genetic differences between limited and extensively passaged human cytomegalovirus strains. Rev Med Virol 11(3):191–200

    Article  PubMed  CAS  Google Scholar 

  39. Puchhammer-Stockl E, Gorzer I (2006) Cytomegalovirus and Epstein-Barr virus subtypes—the search for clinical significance. J Clin Virol 36(4):239–248

    Article  PubMed  CAS  Google Scholar 

  40. Puchhammer-Stockl E, Gorzer I, Zoufaly A, Jaksch P, Bauer CC, Klepetko W, Popow-Kraupp T (2006) Emergence of multiple cytomegalovirus strains in blood and lung of lung transplant recipients. Transplantation 81(2):187–194

    Article  PubMed  Google Scholar 

  41. Rasmussen L (1999) Molecular pathogenesis of human cytomegalovirus infection. Transpl Infect Dis 1(2):127–134

    Article  PubMed  CAS  Google Scholar 

  42. Rasmussen L, Geissler A, Winters M (2003) Inter- and intragenic variations complicate the molecular epidemiology of human cytomegalovirus. J Infect Dis 187(5):809–819

    Article  PubMed  Google Scholar 

  43. Sarcinella L, Mazzulli T, Willey B, Humar A (2002) Cytomegalovirus glycoprotein B genotype does not correlate with outcomes in liver transplant patients. J Clin Virol 24(1–2):99–105

    Article  PubMed  CAS  Google Scholar 

  44. Shepp DH, Match ME, Lipson SM, Pergolizzi RG (1998) A fifth human cytomegalovirus glycoprotein B genotype. Res Virol 149(2):109–114

    Article  PubMed  CAS  Google Scholar 

  45. Stanton R, Westmoreland D, Fox JD, Davison AJ, Wilkinson GW (2005) Stability of human cytomegalovirus genotypes in persistently infected renal transplant recipients. J Med Virol 75(1):42–46

    Article  PubMed  CAS  Google Scholar 

  46. Tanaka K, Numazaki K, Tsutsumi H (2005) Human cytomegalovirus genetic variability in strains isolated from Japanese children during 1983–2003. J Med Virol 76(3):356–360

    Article  PubMed  CAS  Google Scholar 

  47. Torok-Storb B, Boeckh M, Hoy C, Leisenring W, Myerson D, Gooley T (1997) Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation. Blood 90(5):2097–2102

    PubMed  CAS  Google Scholar 

  48. Trincado DE, Scott GM, White PA, Hunt C, Rasmussen L, Rawlinson WD (2000) Human cytomegalovirus strains associated with congenital and perinatal infections. J Med Virol 61(4):481–487

    Article  PubMed  CAS  Google Scholar 

  49. Vilas Boas LS, de Souza VA, Penalva de Oliveira AC, Rodriguez Viso AT, Nascimento Filho AM, Nascimento MC, Pannuti CS (2003) Cytomegalovirus glycoprotein B genotypes and central nervous system disease in AIDS patients. J Med Virol 71(3):404–407

    Article  PubMed  CAS  Google Scholar 

  50. Yu ZS, Zou CC, Zheng JY, Zhao ZY (2006) Cytomegalovirus gB genotype and clinical features in Chinese infants with congenital infections. Intervirology 49(5):281–285

    Article  PubMed  Google Scholar 

  51. Zipeto D, Hong C, Gerna G, Zavattoni M, Katzenstein D, Merigan TC, Rasmussen L (1998) Geographic and demographic differences in the frequency of human cytomegalovirus gB genotypes 1–4 in immunocompromised patients. AIDS Res Hum Retroviruses 14(6):533–536

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Phillip E. Pellett, Naoki Nozawa, and Kenji Fujieda for their intellectual input, and Risa Taniguchi and Hitomi Komura for their technical assistance. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, a Grant for Child Health and Development from the Ministry of Health and Welfare, Japan (NI), and a fellowship from the Atsumi Foundation (HY).

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Correspondence to Naoki Inoue.

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Yan, H., Koyano, S., Inami, Y. et al. Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children. Arch Virol 153, 667–674 (2008). https://doi.org/10.1007/s00705-008-0044-7

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  • DOI: https://doi.org/10.1007/s00705-008-0044-7

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