Log in

Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product

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

Abstract

The betaherpesvirus human herpesvirus 6 (HHV-6) has two variants. The U83 gene product of strain HST is a chemoattractant for monocytes. Here, we describe U83 gene variations that accumulated in variants A and B. A gene-variation hot spot was examined in 36 different strains and one donor DNA sample. U83 gene variations accumulated in variant A and in reactivated variant B after transplantation. None of the variant-A viruses encoded the signal peptide found in the B variant. U83 gene sequencing suggested that the variant A and B groups were separate, and that the variant B viruses could be further divided into the HST-Z29 type and another type with a shorter signal peptide. In a eukaryotic expression system, the HST-Z29 type of U83 gene product was secreted into the medium, a frame-shifted HST-Z29 type was partially secreted, and the variant-A type and a first-methionine knockout of the HST-Z29 type were not secreted.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Salahuddin SZ, Ablashi DV, Markham P, Josephs SF, Sturzegger S, Kaplan M, Halligan G, Biberfeld P, Wong-Staal F, Kramarsky B, Gallo RC (1986) Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234:596–601

    Article  PubMed  CAS  Google Scholar 

  2. Lusso P, Markham PD, Tschachler E, di Marzo Veronese F, Salahuddin SZ, Ablashi DV, Pahwa S, Krohn K, Gallo RC (1988) In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). J Exp Med 167:1659–1670

    Article  PubMed  CAS  Google Scholar 

  3. Takahashi K, Sonoda S, Higashi K, Kondo T, Takahashi H, Takahashi M, Yamanishi K (1989) Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus. J Virol 63:3161–3163

    PubMed  CAS  Google Scholar 

  4. Kondo K, Kondo T, Okuno T, Takahashi M, Yamanishi K (1991) Latent human herpesvirus 6 infection of human monocytes/macrophages. J Gen Virol 72:1401–1408

    Article  PubMed  CAS  Google Scholar 

  5. Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T (1988) Identification of human herpesvirus-6 as a causal agent for exanthema subitum. Lancet 1:1065–1067

    Article  PubMed  CAS  Google Scholar 

  6. Ablashi DV, Balachandran N, Josephs SF, Hung CL, Krueger GR, Kramarsky B, Salahuddin SZ, Gallo RC (1991) Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates. Virology 184:545–552

    Article  PubMed  CAS  Google Scholar 

  7. Akhyani N, Berti R, Brennan MB, Soldan SS, Eaton JM, McFarland HF, Jacobson S (2000) Tissue distribution and variant characterization of human herpesvirus (HHV)-6: increased prevalence of HHV-6A in patients with multiple sclerosis. J Infect Dis 182:1321–1325

    Article  PubMed  CAS  Google Scholar 

  8. Aubin JT, Collandre H, Candotti D, Ingrand D, Rouzioux C, Burgard M, Richard S, Huraux JM, Agut H (1991) Several groups among human herpesvirus 6 strains can be distinguished by Southern blotting and polymerase chain reaction. J Clin Microbiol 29:367–372

    PubMed  CAS  Google Scholar 

  9. Chandran B, Tirawatnapong S, Pfeiffer B, Ablashi DV (1992) Antigenic relationships among human herpesvirus-6 isolations. J Med Virol 37:247–254

    Article  PubMed  CAS  Google Scholar 

  10. Gompels UA, Carrigan DR, Carss AL, Arno J (1993) Two groups of human herpesvirus 6 identified by sequence analyses of laboratory strains and variants from Hodgkin’s lymphoma and bone marrow transplant patients. J Gen Virol 74:613–622

    Article  PubMed  CAS  Google Scholar 

  11. Schirmer EC, Wyatt LS, Yamanishi K, Rodriguez WJ, Frenkel N (1991) Differentiation between two distinct classes of viruses now classified as human herpesvirus 6. Proc Natl Acad Sci USA 88:5922–5926

    Article  PubMed  CAS  Google Scholar 

  12. Wyatt LS, Balachandran N, Frenkel N (1990) Variations in the replication and antigenic properties of human herpesvirus 6 strains. J Infect Dis 162:852–857

    PubMed  CAS  Google Scholar 

  13. Yamamoto T, Mukai T, Kondo K, Yamanishi K (1994) Variation of DNA sequence in immediate-early gene of human herpesvirus 6 and variant identification by PCR. J Clin Microbiol 32:473–476

    PubMed  CAS  Google Scholar 

  14. Aubin JT, Agut H, Collandre H, Yamanishi K, Chandran B, Montagnier L, Huraux JM (1993) Antigenic and genetic differentiation of the two putative types of human herpes virus 6. J Virol Methods 41:223–234

    Article  PubMed  CAS  Google Scholar 

  15. Isegawa Y, Mukai T, Nakano K, Kagawa M, Chen J, Mori Y, Sunagawa T, Kawanishi K, Sashihara J, Hata A, Zou P, Kosuge H, Yamanishi K (1999) Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B. J Virol 73:8053–8063

    PubMed  CAS  Google Scholar 

  16. Zou P, Isegawa Y, Nakano K, Haque M, Horiguchi Y, Yamanishi K (1999) Human herpesvirus 6 open reading frame U83 encodes a functional chemokine. J Virol 73:5926–5933

    PubMed  CAS  Google Scholar 

  17. Lopez C, Pellett P, Stewart J, Goldsmith C, Sanderlin K, Black J, Warfield D, Feorino P (1988) Characteristics of human herpesvirus-6. J Infect Dis 157:1271–1273

    PubMed  CAS  Google Scholar 

  18. Downing RG, Sewankambo N, Serwadda D, Honess R, Crawford D, Jarrett R, Griffin BE (1987) Isolation of human lymphotropic herpesvirus from Uganda. Lancet ii:390

  19. Enders G, Biber M, Meyer G, Helftenbein E (1990) Prevalence of antibodies to human herpesvirus 6 in different age groups, in children with exanthema subitum, other acute exanthematous childhood diseases, Kawasaki syndrome, and acute infections with other herpesvirus and HIV. Infection 18:12–15

    Article  PubMed  CAS  Google Scholar 

  20. Krueger GRF, Sander C, Hoffmann A, Barth A, Koch B, Braun M (1991) Isolation of human herpesvirus-6 (HHV-6) from patients with collagen vascular diseases. In Vivo 5:217–226

    PubMed  CAS  Google Scholar 

  21. Isegawa Y, Hara J, Amo K, Osugi Y, Takemoto M, Yamanishi K, Fukunaga R, Shibata M, Ohshima A, Horiguchi Y, Sugimoto N (2009) Human herpesvirus 6 ganciclovir-resistant strain with amino acid substitutions associated with the death of an allogeneic stem cell transplant recipient. J Clin Virol 44:15–19

    Google Scholar 

  22. Isegawa Y, Miyamoto Y, Yasuda Y, Semi K, Tsujimura K, Fukunaga R, Ohshima A, Horiguchi Y, Yoneda Y, Sugimoto N (2008) Characterization of the human herpesvirus 6 U69 gene product and identification of its nuclear localization signal. J Virol 82:710–718

    Article  PubMed  CAS  Google Scholar 

  23. Gompels UA, Nicholas J, Lawrence G, Jones M, Thomson BJ, Martin ME, Efstathiou S, Craxton M, Macaulay HA (1995) The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology 209:29–51

    Article  PubMed  CAS  Google Scholar 

  24. Dominguez G, Dambaugh TR, Stamey FR, Dewhurst S, Inoue N, Pellett PE (1999) Human herpesvirus 6B genome sequence: Coding content and comparison with human herpesvirus 6A. J Virol 73:8040–8052

    PubMed  CAS  Google Scholar 

  25. Isegawa Y, Takemoto M, Yamanishi K, Ohshima A, Sugimoto N (2007) Real-time PCR determination of human herpesvirus 6 antiviral drug susceptibility. J Virol Methods 140:25–31

    Article  PubMed  CAS  Google Scholar 

  26. Dewin DR, Catusse J, Gompels UA (2006) Identification and characterization of U83A viral chemokine, a broad and potent β-chemokine agonist for human CCRs with unique selectivity and inhibition by spliced isoform. J Immun 176:544–556

    PubMed  CAS  Google Scholar 

  27. Catusse J, Parry CM, Dewin DR, Gompels UA (2007) Inhibition of HIV-1 infection by viral chemokine U83A via high-affinity CCR5 interactions that block human chemokine-induced leukocyte chemotaxis and receptor internalization. Blood 109:3633–3639

    Article  PubMed  CAS  Google Scholar 

  28. French C, Menegazz P, Nicholson L, Macaulay H, DiLuca D, Gompels UA (1999) Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6. Virology 262:139–151

    Article  PubMed  CAS  Google Scholar 

  29. Mori Y, Seya T, Huang HL, Akkapaiboon P, Dhepakson P, Yamanishi K (2002) Human herpesvirus 6 variant A but not variant B induces fusion from without in a variety of human cells through a human herpesvirus 6 entry receptor, CD46. J Virol 76:6750–6761

    Article  PubMed  CAS  Google Scholar 

  30. Meeuwsen S, Persoon-Deen C, Bsibsi M, Bajramovic JJ, Ravid R, De Bolle L, van Noort JM (2005) Modulation of the cytokine network in human adult astrocytes by human herpesvirus-6A. J Neuroimmunol 164:37–47

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the clinical staff, especially Dr. K. Tanaka-Taya and Dr. Y. Yamagishi, of the Department of Pediatrics, Graduate School of Medicine, Osaka University, for their help in collecting the ES virus samples and the DNA sample of Japanese HHV-6A.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuji Isegawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sjahril, R., Isegawa, Y., Tanaka, T. et al. Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product. Arch Virol 154, 273–283 (2009). https://doi.org/10.1007/s00705-008-0307-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-008-0307-3

Keywords

Navigation