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. 1988 May 1;167(5):1659–1670. doi: 10.1084/jem.167.5.1659

In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6)

PMCID: PMC2188940  PMID: 3259254

Abstract

We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV- infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV- infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL- 2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.

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Selected References

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  1. Ablashi D. V., Salahuddin S. Z., Josephs S. F., Imam F., Lusso P., Gallo R. C., Hung C., Lemp J., Markham P. D. HBLV (or HHV-6) in human cell lines. Nature. 1987 Sep 17;329(6136):207–207. doi: 10.1038/329207a0. [DOI] [PubMed] [Google Scholar]
  2. Acuto O., Hussey R. E., Fitzgerald K. A., Protentis J. P., Meuer S. C., Schlossman S. F., Reinherz E. L. The human T cell receptor: appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors. Cell. 1983 Oct;34(3):717–726. doi: 10.1016/0092-8674(83)90528-7. [DOI] [PubMed] [Google Scholar]
  3. Biberfeld P., Kramarsky B., Salahuddin S. Z., Gallo R. C. Ultrastructural characterization of a new human B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease. J Natl Cancer Inst. 1987 Nov;79(5):933–941. [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Downing R. G., Sewankambo N., Serwadda D., Honess R., Crawford D., Jarrett R., Griffin B. E. Isolation of human lymphotropic herpesviruses from Uganda. Lancet. 1987 Aug 15;2(8555):390–390. doi: 10.1016/s0140-6736(87)92403-2. [DOI] [PubMed] [Google Scholar]
  6. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  7. Groopman J. E., Sullivan J. L., Mulder C., Ginsburg D., Orkin S. H., O'Hara C. J., Falchuk K., Wong-Staal F., Gallo R. C. Pathogenesis of B cell lymphoma in a patient with AIDS. Blood. 1986 Mar;67(3):612–615. [PubMed] [Google Scholar]
  8. Josephs S. F., Salahuddin S. Z., Ablashi D. V., Schachter F., Wong-Staal F., Gallo R. C. Genomic analysis of the human B-lymphotropic virus (HBLV). Science. 1986 Oct 31;234(4776):601–603. doi: 10.1126/science.3020691. [DOI] [PubMed] [Google Scholar]
  9. Komaroff A. L. The 'chronic mononucleosis' syndromes. Hosp Pract (Off Ed) 1987 May 30;22(5A):71–75. [PubMed] [Google Scholar]
  10. Larocca L. M., Piantelli M., Maggiano N., Musiani P. T cell surface markers expression by immature human thymocytes in in vitro culture: role of Ia+ accessory cells. J Immunol. 1987 Apr 15;138(8):2410–2416. [PubMed] [Google Scholar]
  11. Lea T., Vartdal F., Davies C., Ugelstad J. Magnetic monosized polymer particles for fast and specific fractionation of human mononuclear cells. Scand J Immunol. 1985 Aug;22(2):207–216. doi: 10.1111/j.1365-3083.1985.tb01873.x. [DOI] [PubMed] [Google Scholar]
  12. Lusso P., Salahuddin S. Z., Ablashi D. V., Gallo R. C., Di Marzo Veronese F., Markham P. D. Diverse tropism of HBLV (human herpesvirus 6) Lancet. 1987 Sep 26;2(8561):743–743. doi: 10.1016/s0140-6736(87)91103-2. [DOI] [PubMed] [Google Scholar]
  13. Mann D. L., DeSantis P., Mark G., Pfeifer A., Newman M., Gibbs N., Popovic M., Sarngadharan M. G., Gallo R. C., Clark J. HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis. Science. 1987 May 29;236(4805):1103–1106. doi: 10.1126/science.2883731. [DOI] [PubMed] [Google Scholar]
  14. Pelicci P. G., Knowles D. M., 2nd, Arlin Z. A., Wieczorek R., Luciw P., Dina D., Basilico C., Dalla-Favera R. Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. J Exp Med. 1986 Dec 1;164(6):2049–2060. doi: 10.1084/jem.164.6.2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  16. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986 Oct 31;234(4776):596–601. doi: 10.1126/science.2876520. [DOI] [PubMed] [Google Scholar]
  18. Spits H., Borst J., Tax W., Capel P. J., Terhorst C., de Vries J. E. Characteristics of a monoclonal antibody (WT-31) that recognizes a common epitope on the human T cell receptor for antigen. J Immunol. 1985 Sep;135(3):1922–1928. [PubMed] [Google Scholar]
  19. Tedder R. S., Briggs M., Cameron C. H., Honess R., Robertson D., Whittle H. A novel lymphotropic herpesvirus. Lancet. 1987 Aug 15;2(8555):390–392. doi: 10.1016/s0140-6736(87)92404-4. [DOI] [PubMed] [Google Scholar]
  20. Wieczorek R., Burke J. S., Knowles D. M., 2nd Leu-M1 antigen expression in T-cell neoplasia. Am J Pathol. 1985 Dec;121(3):374–380. [PMC free article] [PubMed] [Google Scholar]

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