Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID- hu Thy/Liv mice

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1953-1960
Number of pages8
JournalJournal of Experimental Medicine
Volume189
Issue number12
DOIs
Publication statusPublished - Jun 21 1999

Keywords

  • Acquired immunodeficiency syndrome
  • Polymerase chain reaction
  • T lymphocyte subsets flow cytometry
  • Thymus gland

ASJC Scopus subject areas

  • Immunology

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