Skip to main content

Advertisement

SpringerLink
Log in

Analysis of human cytomegalovirus glycoprotein N genotypes in Chinese hematopoietic stem cell transplant recipients

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Human cytomegalovirus (HCMV) genomic polymorphisms have been used to investigate correlations between virus variants and clinical characteristics. We explored the distribution of HCMV glycoprotein N (gN) genotypes and their roles relative to clinical features in a population of Chinese hematopoietic stem cell transplant (HSCT) recipients. This prospective analysis involved HCMV clinical isolates obtained from 102 HSCT patients. Real-time quantitative PCR and PCR-based restriction fragment length polymorphism analysis were applied for the determination of viral loads and gN genotypes. The distribution of HCMV gN genotypes was as follows: gN1, 6/102 (5.9%); gN2, 10/102 (9.8%); gN3a, 17/102 (16.7%); gN3b, 5/102 (4.9%); gN4a, 12/102 (11.7%); gN4b, 9/102 (8.8%); gN4d, 2/102 (2.0%); and mixtures, 41/102 (40.2%). No particular HCMV gN genotype was significantly associated with specific clinical characteristics. The HCMV gN3a genotype was the most prevalent among Chinese HSCT recipients, but HCMV gN genotypes may have no correlation with clinical features in HSCT patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Eckle T, Prix L, Jahn G, Klingebiel T, Handgretinger R, Selle B, Hamprecht K (2000) Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood 96(9):3286–3289

    CAS  PubMed  Google Scholar 

  2. Hamprecht K, Eckle T, Prix L, Faul C, Einsele H, Jahn G (2003) Ganciclovir-resistant cytomegalovirus disease after allogeneic stem cell transplantation: Pitfalls of phenotypic diagnosis by in vitro selection of an ul97 mutant strain. J Infect Dis 187(1):139–143. doi:10.1086/346240

    Article  CAS  PubMed  Google Scholar 

  3. Eckle T, Lang P, Prix L, Jahn G, Klingebiel T, Handgretinger R, Selle B, Niethammer D, Hamprecht K (2002) Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant 30(7):433–439. doi:10.1038/sj.bmt.1703666

    Article  CAS  PubMed  Google Scholar 

  4. Marfori JE, Exner MM, Marousek GI, Chou S, Drew WL (2007) Development of new cytomegalovirus ul97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients. J Clin Virol 38(2):120–125. doi:10.1016/j.jcv.2006.11.005

    Article  CAS  PubMed  Google Scholar 

  5. Chou S, Dennison K (1991) Analysis of interstrain variation in cytomegalovirus glycoprotein b sequences encoding neutralization-related epitopes. J Infect Dis 163(6):1229–1234

    CAS  PubMed  Google Scholar 

  6. Pignatelli S, Dal Monte P, Landini M (2001) Gpul73 (gn) genomic variants of human cytomegalovirus isolates are clustered into four distinct genotypes. J Gen Virol 82(Pt 11):2777–2784

    CAS  PubMed  Google Scholar 

  7. Pignatelli S, Dal Monte P, Rossini G, Chou S, Gojobori T, Hanada K, Guo J, Rawlinson W, Britt W, Mach M, Landini M (2003) Human cytomegalovirus glycoprotein n (gpul73-gn) genomic variants: Identification of a novel subgroup, geographical distribution and evidence of positive selective pressure. J Gen Virol 84(Pt 3):647–655

    Article  CAS  PubMed  Google Scholar 

  8. Paterson D, Dyer A, Milne R, Sevilla-Reyes E, Gompels U (2002) A role for human cytomegalovirus glycoprotein o (go) in cell fusion and a new hypervariable locus. Virology 293(2):281–294. doi:10.1006/viro.2001.1274

    Article  CAS  PubMed  Google Scholar 

  9. Chou S (1992) Molecular epidemiology of envelope glycoprotein h of human cytomegalovirus. J Infect Dis 166(3):604–607

    CAS  PubMed  Google Scholar 

  10. Rasmussen L, Geissler A, Cowan C, Chase A, Winters M (2002) The genes encoding the gcIII complex of human cytomegalovirus exist in highly diverse combinations in clinical isolates. J Virol 76(21):10841–10848

    Article  CAS  PubMed  Google Scholar 

  11. Isaacson M, Compton T (2009) Human cytomegalovirus glycoprotein b is required for virus entry and cell-to-cell spread but not for virion attachment, assembly, or egress. J Virol 83(8):3891–3903. doi:10.1128/JVI.01251-08

    Article  CAS  PubMed  Google Scholar 

  12. Britt W, Vugler L, Stephens E (1988) Induction of complement-dependent and -independent neutralizing antibodies by recombinant-derived human cytomegalovirus gp55–116 (gb). J Virol 62(9):3309–3318

    CAS  PubMed  Google Scholar 

  13. Navarro D, Paz P, Tugizov S, Topp K, La Vail J, Pereira L (1993) Glycoprotein b of human cytomegalovirus promotes virion penetration into cells, transmission of infection from cell to cell, and fusion of infected cells. Virology 197(1):143–158. doi:10.1006/viro.1993.1575

    Article  CAS  PubMed  Google Scholar 

  14. Shepp D, Match M, Lipson S, Pergolizzi R (1998) A fifth human cytomegalovirus glycoprotein b genotype. Res Virol 149(2):109–114. doi:S0923251698800861

    Article  CAS  PubMed  Google Scholar 

  15. Trincado D, Scott G, White P, Hunt C, Rasmussen L, Rawlinson W (2000) Human cytomegalovirus strains associated with congenital and perinatal infections. J Med Virol 61(4):481–487. doi:10.1002/1096-9071

    Article  CAS  PubMed  Google Scholar 

  16. Kari B, Gehrz R (1993) Structure, composition and heparin binding properties of a human cytomegalovirus glycoprotein complex designated gc-II. J Gen Virol 74(Pt 2):255–264

    Article  CAS  PubMed  Google Scholar 

  17. Mach M, Kropff B, Dal Monte P, Britt W (2000) Complex formation by human cytomegalovirus glycoproteins m (gpul100) and n (gpul73). J Virol 74(24):11881–11892

    Article  CAS  PubMed  Google Scholar 

  18. Dal Monte P, Pignatelli S, Mach M, Landini MP (2001) The product of human cytomegalovirus UL73 is a new polymorphic structural glycoprotein (gpUL73). J Hum Virol 4(1):26–34

    CAS  PubMed  Google Scholar 

  19. Bates M, Monze M, Bima H, Kapambwe M, Kasolo FC, Gompels UA (2008) High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa. Virology 382(1):28–36. doi:10.1016/j.virol.2008.09.001

    Article  CAS  PubMed  Google Scholar 

  20. Manuel O, Pang XL, Humar A, Kumar D, Doucette K, Preiksaitis JK (2009) An assessment of donor-to-recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants. J Infect Dis 199(11):1621–1628. doi:10.1086/598952

    Article  CAS  PubMed  Google Scholar 

  21. Urban M, Britt W, Mach M (1992) The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of human cytomegalovirus is strain specific. J Virol 66(3):1303–1311

    CAS  PubMed  Google Scholar 

  22. 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. doi:10.1016/j.virol.2003.09.036

    Article  CAS  PubMed  Google Scholar 

  23. Yan H, Koyano S, Inami Y, Yamamoto Y, Suzutani T, Mizuguchi M, Ushijima H, Kurane I, Inoue N (2008) Genetic linkage among human cytomegalovirus glycoprotein N (gN) and go genes, with evidence for recombination from congenitally and post-natally infected Japanese infants. J Gen Virol 89(Pt 9):2275–2279. doi:10.1099/vir.0.83685-0

    Article  CAS  PubMed  Google Scholar 

  24. Woo P, Lo C, Lo S, Siau H, Peiris J, Wong S, Luk W, Chan T, Lim W, Yuen K (1997) Distinct genotypic distributions of cytomegalovirus (CMV) envelope glycoprotein in bone marrow and renal transplant recipients with CMV disease. Clin Diagn Lab Immunol 4(5):515–518

    CAS  PubMed  Google Scholar 

  25. 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

    CAS  PubMed  Google Scholar 

  26. Wu X, Wang Y, Xu Y, Wu D, Sun A, Zhu Z, Han Y, Qiu H, Tang X, Fu Z, He G, Li C, Ma X, Liu Y (2010) Cytomegalovirus glycoprotein b genotype in hematopoietic stem cell transplant patients from china. Biol Blood Marrow Transplant 16(5):647–652. doi:10.1016/j.bbmt.2009.12.001

    Article  CAS  PubMed  Google Scholar 

  27. Pignatelli S, Dal Monte P, Rossini G, Camozzi D, Toscano V, Conte R, Landini M (2006) Latency-associated human cytomegalovirus glycoprotein N genotypes in monocytes from healthy blood donors. Transfusion 46(10):1754–1762. doi:10.1111/j.1537-2995.2006.00963.x

    Article  CAS  PubMed  Google Scholar 

  28. Pignatelli S, Dal Monte P, Rossini G, Lazzarotto T, Gatto M, Landini M (2003) Intrauterine cytomegalovirus infection and glycoprotein N (gN) genotypes. J Clin Virol 28(1):38–43. doi:S1386653202002366

    Article  CAS  PubMed  Google Scholar 

  29. Novak Z, Ross SA, Patro RK, Pati SK, Kumbla RA, Brice S, Boppana SB (2008) Cytomegalovirus strain diversity in seropositive women. J Clin Microbiol 46(3):882–886. doi:10.1128/JCM.01079-07

    Article  CAS  PubMed  Google Scholar 

  30. Chen HP, Lin JC, Yang SP, Lan YC, Weng WS, Tsai CH, Ho DM, Liu CY, Cho WL, Chan YJ (2008) The type-2 variant of human cytomegalovirus glycoprotein N (gN-2) is not the rarest in the chinese population of taiwan: Influence of primer design. J Virol Methods 151(1):161–164. doi:10.1016/j.jviromet.2008.03.018

    Article  CAS  PubMed  Google Scholar 

  31. Pignatelli S, Dal Monte P (2009) Epidemiology of human cytomegalovirus strains through comparison of methodological approaches to explore gN variants. New Microbiol 32(1):1–10

    CAS  PubMed  Google Scholar 

  32. Pignatelli S, Lazzarotto T, Gatto MR, Dal Monte P, Landini MP, Faldella G, Lanari M (2010) Cytomegalovirus gN genotypes distribution among congenitally infected newborns and their relationship with symptoms at birth and sequelae. Clin Infect Dis 51(1):33–41. doi:10.1086/653423

    Article  CAS  PubMed  Google Scholar 

  33. 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. doi:10.1097/01.tp.0000194858.50812

    Article  PubMed  Google Scholar 

  34. Rossini G, Pignatelli S, Dal Monte P, Camozzi D, Lazzarotto T, Gabrielli L, Gatto MR, Landini MP (2005) Monitoring for human cytomegalovirus infection in solid organ transplant recipients through antigenemia and glycoprotein N (gN) variants: evidence of correlation and potential prognostic value of gN genotypes. Microbes Infect 7(5–6):890–896. doi:10.1016/j.micinf.2005.01.016

    Article  CAS  PubMed  Google Scholar 

  35. Pignatelli S, Rossini G, Dal Monte P, Gatto MR, Landini MP (2003) Human cytomegalovirus glycoprotein n genotypes in aids patients. AIDS 17(5):761–763. doi:10.1097/01.aids

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Xiao-tao Zhao, Yan-rong Zhang and Yuan-yuan Sun for helping us to collect plasma samples.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Peking University People’s Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Chang-sheng Xia & Zheng Zhang

Authors
  1. Chang-sheng Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zheng Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xia, Cs., Zhang, Z. Analysis of human cytomegalovirus glycoprotein N genotypes in Chinese hematopoietic stem cell transplant recipients. Arch Virol 156, 17–23 (2011). https://doi.org/10.1007/s00705-010-0811-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-010-0811-0

Keywords

Search

Navigation