1887

Abstract

Fifteen human herpesvirus 6 (HHV-6) strain variants were analysed by PCR amplifications, restriction enzyme site polymorphism and sequence analyses. Three DNA regions were chosen for study: a fragment of a variable glycoprotein gene (210 bp), the conserved glycoprotein H (gH) gene complete with intergenic sequences (2381 bp) and the 5′ intergenic region with the N-terminal coding sequence of gH up to a polymorphic HI site (427 bp). Infected cell DNA from five laboratory reference strains including GS, U1102, AJ, Z29 and KF were examined together with DNA from peripheral blood blymphocytes infected with HHV-6 reactivated from blood and/or marrow from five bone marrow transplant (BMT) patients. Separate blood and marrow isolates were obtained from four BMT patients. In addition, HHV-6 sequences were examined directly from one of six Hodgkin′s lymphomas and six B cell proliferations which contained HHV-6 DNA as detected by PCR amplification. The results show two groups of very closely related but heterogeneous strains which correlate with previous groupings by antigenic and restriction site differences. These are variant A strains (including laboratory strains GS, U1102 and AJ) and variant B strains (including laboratory strains Z29 and KF, the Hodgkin′s lymphoma strain, and the nine BMT patient isolates). Variations between the groups were 4 to 6% in nucleotide sequence and 5 to 8∙5% in amino acid sequence. Within each group maximum heterogeneity was observed in different genes. Variant A strains differed by 2∙0% in the variable glycoprotein gene sequence whereas variant B strains were identical in this region; conversely, variant B strains differed by 2 to 3% in the gH N-terminal and intergenic sequences whereas variant A strains differed there by less than 0∙2%. There was evidence for sequence drift independent of selection: relationships between the groups were shown by analyses of amino acid sequence, coding nucleotide sequence as well as intergenic sequence, and the B variant-specific HI site in the gH gene was due to a non-coding nucleotide substitution. There was little evidence for or variation: the gH nucleotide sequence from the uncultured lymphoma strain (first variant B gH gene identified) was almost identical to the gH sequence from four BMT isolates, and matched BMT isolates from blood and marrow were identical or with a single nucleotide substitution. The overall variation observed between the HHV-6 strain groups was similar or less than that seen between human cytomegalovirus strains such as AD169 or Towne, but clearly distinct from the much greater divergence between currently designated herpesvirus species.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-4-613
1993-04-01
2021-10-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/4/JV0740040613.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-4-613&mimeType=html&fmt=ahah

References

  1. Ablashi A. V., Balachandran N., Josephs S. F., Hung C. L., Krueger GR. F, Kramarsky B., Salahuddin S. Z., Gallo R. C. 1991; Genomic polymorphism, growth properties, and immunological variations in human herpesvirus-6 isolates. Virology 184:545–552
    [Google Scholar]
  2. Asano Y., Yoshikawa T., Suga S., Yazaki T., Kondo K., Yamanishi K. 1990; Fatal fulminant hepatitis in an infant with human herpesvirus-6 infection. Lancet 335:862–863
    [Google Scholar]
  3. Aubin J. T., Collandre H., Candotti D., Ingrand D., Rouzioux C., Burgard M., Richard S., Huraux J. M., Agut H. 1991; Several groups among human herpesvirus 6 strains can be distinguished by Southern blotting and polymerase chain reaction. Journal of Clinical Microbiology 29:367–372
    [Google Scholar]
  4. Aubin J. T., Agut H., Collandre H., Yamanishi K., Chandran B., Montagnier L., Huraux J.-M. 1993; Antigenic and genetic differentiation of the two putative types of human herpesvirus 6. Journal of Virological Methods (in press)
    [Google Scholar]
  5. Biggin M. D., Gibson T. J., Hong C. F. 1983; Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proceedings of the National Academy of Sciences, U.S.A. 80:3963–3965
    [Google Scholar]
  6. Briggs M., Fox J. D., Tedder R. S. 1988; Age prevalence of antibody to human herpesvirus 6. Lancet i:1058–1059
    [Google Scholar]
  7. Abouzid A. M., Hiebert E. 1991; Characterization of a Florida tomato geminivirus (FTGV). Phytopathology :81–1184
    [Google Scholar]
  8. Carrigan D. R., Knox K. K., Tapper M. A. 1990; Suppression of human immunodeficiency virus type 1 replication by human herpesvirus-6. Journal of Infectious Diseases 162:844–851
    [Google Scholar]
  9. Carrigan D. R., Drobyski W. R., Russler S. K., Tapper M. A., Knox K. K., Ash R. C. 1991; Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet 338:147–149
    [Google Scholar]
  10. Chandran B., Tirawatnapang S., Pfeiffer B., Ablashi D. V. 1992; Antigenic relationships among human herpesvirus-6 isolates. Journal of Medical Virology 37:247–254
    [Google Scholar]
  11. Chee M. S., Bankier T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchinson C. A., Ill, Kouzarides T., Martignetti J. A., Preddie E., Satchwell S. C., Tomlinson P., Weston K. M., Barrell B. G. 1990; Analysis of the protein coding content of the sequence of human cytomegalovirus strain AD169. Current Topics in Microbiology and Immunology 154:125–169
    [Google Scholar]
  12. Chou S. 1992; Molecular epidemiology of envelope glycoprotein H of HCMV. Journal of Infectious Diseases 166:604–607
    [Google Scholar]
  13. Chou S., Dennison K. M. 1991; Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. Journal of Infectious Diseases 163:1229–1234
    [Google Scholar]
  14. Chou S., Marousek G. I. 1992; Homology of the envelope glycoprotein B of human herpesvirus-6 and cytomegalovirus. Virology 191:523–528
    [Google Scholar]
  15. Davison A. J., Taylor P. 1987; Genetic relations between varicella-zoster virus and Epstein-Barr virus. Journal of General Virology 68:1067–1079
    [Google Scholar]
  16. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Research 12:387–395
    [Google Scholar]
  17. Dewhurst S., Chandran B., McIntyre K., Schnabel K., Hall C. B. 1992; Phenotypic and genetic polymorphisms among human herpesvirus-6 isolates from North American infants. Virology (in press)
    [Google Scholar]
  18. Downing R. G., Sewankambo N., Serwadda D., Honess R., Crawford D., Jarrett R., Griffin B. E. 1987; Isolation of human lymphotropic herpesviruses from Uganda. Lancet ii:390
    [Google Scholar]
  19. Drobyski W. R., Dunne W. M., Burd E. M., Knox K. K., Ash R. C., Horowitz M. M., Flemenberg N., Carrigan D. R. 1992; Human herpesvirus-6 (HHV-6) infection in allogenic bone marrow transplant recipients. I. Evidence of a marrow suppressive role for HHV-6 in vivo. Journal of Infectious Diseases (in press)
    [Google Scholar]
  20. Efstathiou S., Gompels U., Craxton M., Honess R. W., Ward K. 1988; DNA homology between a novel human herpesvirus (HHV-6) and human cytomegalovirus. Lancet i:63–64
    [Google Scholar]
  21. Ensoli B., Lusso P., Schachter F., Josephs S. F., Rappaport J., Negro F., Gallo R. C., Wong-Staal F. 1989; Human herpesvirus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer. EMBO Journal 8:3019–3027
    [Google Scholar]
  22. Feng D. F., Doolittle R. F. 1987; Progressive sequence alignment as a prerequisite to correct phylogenetic trees. Journal of Molecular Evolution 25:351–360
    [Google Scholar]
  23. Fox J. D., Briggs M., Ward P. A., Tedder R. S. 1990; Human herpesvirus-6 in salivary glands. Lancet 336:590–593
    [Google Scholar]
  24. Gompels U. A., Craxton M. A., Honess R. W. 1988; Conservation of glycoprotein H (gH) in herpesviruses: nucleotide sequence of the gH gene from herpesvirus saimiri. Journal of General Virology 69:2819–2829
    [Google Scholar]
  25. Gompels U. A., Carss A. L., Saxby C., Hancock D. C., Forrester A., Minson A. C. 1991; Characterization and sequence analyses of antibody-selected antigenic variants of herpes simplex virus show a conformationally complex epitope on glycoprotein H. Journal of Virology 65:2393–2401
    [Google Scholar]
  26. Gompels U. A., Carss A. L., Sun N., Arrand J. R. 1992; Infectivity determinants encoded in a conserved gene block of human herpesvirus-6. DNA Sequence: Journal of DNA Sequencing and Mapping 3:25–39
    [Google Scholar]
  27. Josephs S. F., Ablashi D. V., Salahuddin S. Z., Jagodzinski L. L., Wong-Staal F., Gallo C. 1991; Identification of the human herpesvirus-6 glycoprotein H and putative large tegument protein genes. Journal of Virology 65:5597–5604
    [Google Scholar]
  28. Knox K. K., Carrigan D. R. 1992; In vitro suppression of marrow progenitor cell differentiation by human herpesvirus six infection. Journal of Infectious Diseases 165:925–929
    [Google Scholar]
  29. Kondo K., Kondo T., Okuno T., Takahashi M., Yamanishi K. 1991; Latent human herpesvirus 6 infection in monocytes/macrophages. Journal of General Virology 72:1401–1408
    [Google Scholar]
  30. Lawrence G. L., Chee L. M., Craxton M. A., Gompels U. A., Honess R. W., Barrell B. G. 1990; Human herpesvirus 6 is closely related to human cytomegalovirus. Journal of Virology 64:287–299
    [Google Scholar]
  31. Lehner R., Stamminger T., Mach M. 1991; Comparative sequence analysis of human cytomegalovirus strains. Journal of Clinical Microbiology 29:2494–2502
    [Google Scholar]
  32. Levy J. A., Ferro F., Greenspan D., Lennette E. T. 1990a; Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population. Lancet 335:1047–1050
    [Google Scholar]
  33. Levy J. A., Ferro F., Lennette E. T., Oshiro L., Poulin L. 1990b; Characterization of a new strain of HHV-6 (HHV-6SF) recovered from saliva of an HIV infected individual. Virology 178:113–121
    [Google Scholar]
  34. Levy J. A., Landay A., Lennette E. T. 1990c; Human herpesvirus 6 inhibits human immunodeficiency virus type 1 replication in cell culture. Journal of Clinical Microbiology 28:2362–2364
    [Google Scholar]
  35. Lindquester G. J., Pellett P. E. 1991; Properties of the human herpesvirus 6 strain Z29 genome: G and C content, length and presence of variable-length directly repeated terminal sequence elements. Virology 182:102–110
    [Google Scholar]
  36. Lopez C., Pellett P., Stewart J., Goldsmith C., Sanderlin K., Black J., Warfield D., Feorino P. 1988; Characteristics of human herpesvirus-6. Journal of Infectious Diseases 157:1271–1273
    [Google Scholar]
  37. Lusso P., Markham P. D., Tschachler E., di Marzo Veronese F., Salahuddin S. Z., Ablashi D. V., Pahwa S., Krohn K., Gallo R. C. 1988; In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). Journal of Experimental Medicine 167:1659–1670
    [Google Scholar]
  38. Lusso P., Ensoli B., Markham P. D., Ablashi D. V., Salahuddin Z., Tschachler E., Wong-Staal F., Gallo R. C. 1989; Productive dual infection of human CD4+ T lymphocytes by HIV-1 and HHV-6. Nature, London 337:370–373
    [Google Scholar]
  39. Lusso P., De Maria A., Malnati M., DeRoco S. E., Baseler M., Gallo R. C. 1991; Induction of CD4 and susceptibility to HIV-1 infection in human CD8+ lymphocytes by human herpesvirus 6. Nature, London 349:533–535
    [Google Scholar]
  40. McGeoch D. J., Moss H. W., McNab D., Frame M. C. 1987; DNA sequence and genetic content of the HindlW l region in the short unique component of the herpes simplex virus type 2 genomeidentification of the gene encoding glycoprotein G, and evolutionary comparisons. Journal of General Virology 68:19–38
    [Google Scholar]
  41. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. 1988; The complete DNA sequences of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
    [Google Scholar]
  42. Martin ME. D, Thomson B. J., Honess R. W., Teo I., Jones M. D. 1991; The genome of human herpesvirus 6: maps of unit-length and concatemeric genomes for nine restriction endonucleases. Journal of General Virology 72:157–168
    [Google Scholar]
  43. Messing J. 1983; New M13 vectors for cloning. Methods in Enzymology 101:2–78
    [Google Scholar]
  44. Meyer H., Masuho Y., Mach M. 1990; The gpl 16 of the gp58/l 16 complex of human cytomegalovirus represents the aminoterminal part of the precursor molecule and contains a neutralizing epitope. Journal of General Virology 71:2443–2450
    [Google Scholar]
  45. Morris D. J., Little E., Arrand J. R., Jordan D., Mallick N. P., Johnson RW. G. 1989; Human herpesvirus 6 infection in renal transplant recipients. Lancet i:1560–1561
    [Google Scholar]
  46. Myers G. 1990 HIV Sequence Database Los Alamos: Los Alamos National Laboratory;
    [Google Scholar]
  47. Neipel F., Ellinger K., Fleckenstein B. 1991; The unique region of the human herpesvirus 6 genome is essentially collinear with the UL segment of human cytomegalovirus. Journal of General Virology 72:2293–2297
    [Google Scholar]
  48. Nicolson L., Cullinane A. A., Onions D. E. 1990; The nucleotide sequence of an equine herpesvirus 4 gene homologue of the herpes simplex virus 1 glycoprotein H gene. Journal of General Virology 71:1793–1800
    [Google Scholar]
  49. Okuno T., Takahashi K., Balachandra K., Shiraki K., Yama-nishi K., Takahashi M., Baba K. 1989; Seroepidemiology of human herpesvirus 6 infection in normal children and adults. Journal of Clinical Microbiology 27:651–653
    [Google Scholar]
  50. Okuno T., Higashi K., Shiraki K., Takahashi M., Yamanishi K. 1990; Human herpesvirus-6 (HHV-6) infection in renal transplantation. Transplantation 49:519–522
    [Google Scholar]
  51. Pachl C., Probert W. S., Hermsen K. M., Masiarz F. R., Rasmussen L., Merigan T. C., Spaete R. R. 1989; The human cytomegalovirus strain Towne glycoprotein H gene encodes glycoprotein p86. Virology 169:418–126
    [Google Scholar]
  52. Roizman B., Desrosiers R. C., Fleckenstein B., Fleckenstein B. 1991; Characterization of a Florida tomato geminivirus (FTGV). Phytopathology :81–1184
    [Google Scholar]
  53. Roizman B., Desrosiers R. C., Fleckenstein B., Lopez C., Minson A. C., Studdert M. J. 1992; The family herpesviridae: an update. Archives of Virology 123:425–149
    [Google Scholar]
  54. Russler S. K., Tapper M. A., Knox K. K., Liepins A., Carrigan D. R. 1991; Pneumonitis associated with coinfection by human herpesvirus 6 and legionella in an immunocompetent adult. American Journal of Pathology 138:1405–1411
    [Google Scholar]
  55. Sakaoka H., Saito H., Sekine K., Aomori T., Grillner L., Wadell G., Fujinaga K. 1987; Genomic comparison of herpes simplex virus type 1 isolates from Japan, Sweden and Kenya. Journal of General Virology 68:749–764
    [Google Scholar]
  56. Salahuddin S. Z., Ablashi D. V., Markham P. D., Josephs S. F., Sturzenegger S., Kaplan M., Halligan G., Biberfeld P., Wong-Staal F., Kramarsky B., Gallo R. C. 1986; Isolation of a new virus, HBLV, in patients with lymphoproliférative disorders. Science 234:596–601
    [Google Scholar]
  57. Sample J., Young L., Martin B., Chatman T., Kieff E. H., Kieff E. 1990; Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B and EBNA-3C genes. Journal of Virology 64:4084–4092
    [Google Scholar]
  58. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A. 74:5463–5467
    [Google Scholar]
  59. Schirmer E. C., Wyatt L. S., Yamanishi K., Rodriguez W. J., Frenkel N. 1991; Differentiation between two distinct classes of viruses now classified as human herpesvirus-6. Proceedings of the National Academy of Sciences, U.S.A. 88:5922–5926
    [Google Scholar]
  60. 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. Journal of Virology 63:3161–3163
    [Google Scholar]
  61. Tedder R. S., Briggs M., Cameron C. H., Honess R., Robertson D., Whittle H. 1987; A novel lymphotropic herpesvirus. Lancet ii:390–392
    [Google Scholar]
  62. Torrelli G., Marasca R., Luppi M., Selleri L., Ferrari S., Narni F., Mariano M. T., Federico M., Ceccherini-Nelli L., Bendinelli M., Montagnani G., Montorsi M., Artusi T. 1991; Human herpesvirus-6 in human lymphomas: identification of specific sequences in Hodgkin’s lymphoma by polymerase chain reaction. Blood 77:2251–2258
    [Google Scholar]
  63. Urban M., Britt W., Mach M. 1992; The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of human cytomegalovirus is strain specific. Journal of Virology 66:1303–1311
    [Google Scholar]
  64. Ward K. N., Gray J. J., Efstathiou S. 1989; Brief report: primary human herpesvirus-6 infection in a patient following liver transplantation from a seropositive donor. Journal of Medical Virology 28:69–72
    [Google Scholar]
  65. Wrzos H., Gibbons J., Abl P. L., Gifford RR. M, Yang H. C. 1990; Human herpesvirus 6 in monocytes of transplant patients. Lancet 335:486–487
    [Google Scholar]
  66. Wyatt L. S., Balachandran N., Frenkel N. 1990; Variations in the replication and antigenic properties of human herpesvirus 6 strains. Journal of Infectious Diseases 162:852–857
    [Google Scholar]
  67. Yamanishi K., Okuno T., Shiraki K., Takahashi M., Kondo T., Asano U., Kurata T. 1988; Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet i:1065–1067
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-4-613
Loading
/content/journal/jgv/10.1099/0022-1317-74-4-613
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error