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J. Exp. Med.,
Volume 189, Number 12, June 21, 1999 1953-1960
By
From the * Unit of Human Virology, Department of Biological and Technological Research
(DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the 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.
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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