Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.
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21 June 1999
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June 21 1999
Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
Alberto Gobbi,
Alberto Gobbi
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Cheryl A. Stoddart,
Cheryl A. Stoddart
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Mauro S. Malnati,
Mauro S. Malnati
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Giuseppe Locatelli,
Giuseppe Locatelli
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Fabio Santoro,
Fabio Santoro
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Nancy W. Abbey,
Nancy W. Abbey
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Christopher Bare,
Christopher Bare
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Valerie Linquist-Stepps,
Valerie Linquist-Stepps
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Mary Beth Moreno,
Mary Beth Moreno
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Brian G. Herndier,
Brian G. Herndier
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Paolo Lusso,
Paolo Lusso
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Joseph M. McCune
Joseph M. McCune
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
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Alberto Gobbi
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Cheryl A. Stoddart
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Mauro S. Malnati
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Giuseppe Locatelli
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Fabio Santoro
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Nancy W. Abbey
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Christopher Bare
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Valerie Linquist-Stepps
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Mary Beth Moreno
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Brian G. Herndier
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Paolo Lusso
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Joseph M. McCune
From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the ‡Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the §Department of Pathology, University of California, San Francisco, California 94110
Address correspondence to Joseph M. McCune, Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94110-9100. Phone: 415-695-3828; Fax: 415-826-8449; E-mail: mmccune @gladstone.ucsf.edu
Some of the results in this manuscript were presented at the Annual Meeting of the Institute of Human Virology, Baltimore, MD, August 1998.
Received:
March 05 1999
Revision Received:
April 20 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (12): 1953–1960.
Article history
Received:
March 05 1999
Revision Received:
April 20 1999
Citation
Alberto Gobbi, Cheryl A. Stoddart, Mauro S. Malnati, Giuseppe Locatelli, Fabio Santoro, Nancy W. Abbey, Christopher Bare, Valerie Linquist-Stepps, Mary Beth Moreno, Brian G. Herndier, Paolo Lusso, Joseph M. McCune; Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice . J Exp Med 21 June 1999; 189 (12): 1953–1960. doi: https://doi.org/10.1084/jem.189.12.1953
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