{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:39:15Z","timestamp":1790915955176,"version":"4.1.0"},"reference-count":34,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,6,21]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1084\/jem.189.12.1953","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1953-1960","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy\/Liv Mice"],"prefix":"10.1084","volume":"189","author":[{"given":"Alberto","family":"Gobbi","sequence":"first","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl A.","family":"Stoddart","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro S.","family":"Malnati","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Locatelli","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Santoro","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy W.","family":"Abbey","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bare","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Linquist-Stepps","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Moreno","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Herndier","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Lusso","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"McCune","sequence":"additional","affiliation":[{"name":"From the *Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan 20132, Italy; the \u2021Gladstone Institute of Virology and Immunology, San Francisco, California 94110-9100; and the \u00a7Department of Pathology, University of California, San Francisco, California 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,6,21]]},"reference":[{"key":"2023072508232838500_B1","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.2876520","article-title":"Isolation of a new virus, HBLV, in patients with lymphoproliferative 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