Home LiteratureArticle Details
PMID: 2896757 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host.

The Journal of experimental medicine ·Vol. 167 ·No. 5 ·1988-05-01 ·Pages 1645-58

Mutter W, Reddehase MJ, Busch FW, Bühring HJ, Koszinowski UH

Abstract

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able to limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease.

MeSH Terms
Animals Bone Marrow Transplantation Cell Differentiation Cytomegalovirus/physiology Cytomegalovirus Infections/complications,pathology Female Hematopoiesis Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/pathology Immunization, Passive Immunologic Deficiency Syndromes/complications Mice Mice, Inbred BALB C Radiation Chimera T-Lymphocytes, Regulatory/immunology,transplantation Virus Replication
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mutter W
Federal Research Centre for Virus Diseases of Animals, Tübingen, Federal Republic of Germany.
Reddehase M J
Busch F W
Bühring H J
Koszinowski U H
References (36)
36 references, click to expand
  1. Delay in platelet recovery after bone marrow transplantation: impact of cytomegalovirus infection.
    Blood. 1985 Oct;66(4):921-5 PMID: 2994781
  2. Host immune response to cytomegalovirus: products of transfected viral immediate-early genes are recognized by cloned cytolytic T lymphocytes.
    J Virol. 1987 Jun;61(6):2054-8 PMID: 3033334
  3. Cloned long-term cytolytic T-lymphocyte line with specificity for an immediate-early membrane antigen of murine cytomegalovirus.
    J Virol. 1986 Jan;57(1):408-12 PMID: 3001363
  4. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.
    Radiat Res. 1961 Feb;14:213-22 PMID: 13776896
  5. Adoptive immunotherapy of murine cytomegalovirus adrenalitis in the immunocompromised host: CD4-helper-independent antiviral function of CD8-positive memory T lymphocytes derived from latently infected donors.
    J Virol. 1988 Mar;62(3):1061-5 PMID: 2828654
  6. CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity.
    J Virol. 1987 Oct;61(10):3102-8 PMID: 3041033
  7. Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus.
    J Exp Med. 1987 Sep 1;166(3):668-77 PMID: 3040884
  8. Characterization of the major immediate-early polypeptides encoded by murine cytomegalovirus.
    J Virol. 1985 May;54(2):422-8 PMID: 2985805
  9. The cytolytic T lymphocyte response to the murine cytomegalovirus. II. Detection of virus replication stage-specific antigens by separate populations of in vivo active cytolytic T lymphocyte precursors.
    Eur J Immunol. 1984 Jan;14(1):56-61 PMID: 6319154
  10. Megakaryocytopoiesis and granulopoiesis after murine cytomegalovirus infection.
    J Lab Clin Med. 1984 Sep;104(3):381-90 PMID: 6088656
  11. The 89,000-Mr murine cytomegalovirus immediate-early protein activates gene transcription.
    J Virol. 1986 Apr;58(1):59-66 PMID: 3005659
  12. Cytomegalovirus infection following marrow transplantation: risk, treatment, and prevention.
    Birth Defects Orig Artic Ser. 1984;20(1):101-17 PMID: 6329356
  13. Cytotoxic T lymphocyte response to murine cytomegalovirus infection.
    Nature. 1978 Jun 15;273(5663):541-3 PMID: 207997
  14. A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells.
    Cell. 1987 Mar 27;48(6):997-1007 PMID: 2435412
  15. Immediate-early genes of murine cytomegalovirus: location, transcripts, and translation products.
    J Virol. 1987 Feb;61(2):526-33 PMID: 3027381
  16. Transient nature of early haematopoietic spleen colonies.
    Nature. 1982 Feb 11;295(5849):527-9 PMID: 7057912
  17. Persistent production of colony-stimulating factor (CSF-1) by cloned bone marrow stromal cell line D2XRII after X-irradiation.
    J Cell Physiol. 1986 Mar;126(3):407-13 PMID: 3485107
  18. Studies on the morphogenesis of murine cytomegalovirus.
    Intervirology. 1986;26(4):192-201 PMID: 3038772
  19. Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony-stimulating factors.
    Blood. 1987 Feb;69(2):682-91 PMID: 3492227
  20. Sequence and structural organization of murine cytomegalovirus immediate-early gene 1.
    J Virol. 1987 Jun;61(6):1901-8 PMID: 3033321
  21. In vivo application of recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection.
    J Exp Med. 1987 Mar 1;165(3):650-6 PMID: 3029272
  22. Death in the AIDS patient: role of cytomegalovirus.
    N Engl J Med. 1983 Dec 8;309(23):1454 PMID: 6314141
  23. T cell recognition of Moloney leukemia virus proteins. III. T cell proliferative responses against gp70 are associated with the production of a lymphokine inducing 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes.
    J Immunol. 1981 Dec;127(6):2565-70 PMID: 6795277
  24. Hematopoietic factor production by a cell line (TC-1) derived from adherent murine marrow cells.
    Blood. 1985 Aug;66(2):273-81 PMID: 2410062
  25. Reactivation of murine cytomegalovirus by cyclophosphamide.
    Nature. 1977 Jun 23;267(5613):721-3 PMID: 195225
  26. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors.
    Blood. 1986 Feb;67(2):257-67 PMID: 3002522
  27. Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection.
    Nature. 1984 Nov 22-28;312(5992):369-71 PMID: 6095095
  28. A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes.
    J Exp Med. 1987 Jul 1;166(1):289-94 PMID: 2439637
  29. The essential cells of the hemopoietic microenvironment.
    Exp Hematol. 1984 Aug;12(7):517-21 PMID: 6745328
  30. Pathogenesis of pulmonary cytomegalovirus infection in immunosuppressed mice.
    J Infect Dis. 1974 Jun;129(6):677-89 PMID: 4365945
  31. Diversity of haematopoietic stem cell growth from a uniform population of cells.
    Nature. 1986 Jul 17-23;322(6076):289-90 PMID: 2874496
  32. Thrombocytopenia in murine cytomegalovirus infection.
    J Lab Clin Med. 1973 Jan;81(1):53-63 PMID: 4344925
  33. Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs.
    J Virol. 1985 Aug;55(2):264-73 PMID: 2991554
  34. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS.
    Proc Natl Acad Sci U S A. 1964 Jan;51:29-36 PMID: 14104600
  35. Human cytomegalovirus replicates in primary human bone marrow cells.
    J Gen Virol. 1986 Dec;67 ( Pt 12):2595-604 PMID: 3025341
  36. Cultured mouse marrow stromal cell lines. II. Distinct subtypes differing in morphology, collagen types, myelopoietic factors, and leukemic cell growth modulating activities.
    J Cell Physiol. 1985 Jan;122(1):81-90 PMID: 2981238
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1988-05-01
Pages
1645-58
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188951
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com