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Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice

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,...

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Autores principales: Gobbi, Alberto, Stoddart, Cheryl A., Malnati, Mauro S., Locatelli, Giuseppe, Santoro, Fabio, Abbey, Nancy W., Bare, Christopher, Linquist-Stepps, Valerie, Moreno, Mary Beth, Herndier, Brian G., Lusso, Paolo, McCune, Joseph M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192958/
https://www.ncbi.nlm.nih.gov/pubmed/10377191
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author Gobbi, Alberto
Stoddart, Cheryl A.
Malnati, Mauro S.
Locatelli, Giuseppe
Santoro, Fabio
Abbey, Nancy W.
Bare, Christopher
Linquist-Stepps, Valerie
Moreno, Mary Beth
Herndier, Brian G.
Lusso, Paolo
McCune, Joseph M.
author_facet Gobbi, Alberto
Stoddart, Cheryl A.
Malnati, Mauro S.
Locatelli, Giuseppe
Santoro, Fabio
Abbey, Nancy W.
Bare, Christopher
Linquist-Stepps, Valerie
Moreno, Mary Beth
Herndier, Brian G.
Lusso, Paolo
McCune, Joseph M.
author_sort Gobbi, Alberto
collection PubMed
description 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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spelling pubmed-21929582008-04-16 Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice Gobbi, Alberto Stoddart, Cheryl A. Malnati, Mauro S. Locatelli, Giuseppe Santoro, Fabio Abbey, Nancy W. Bare, Christopher Linquist-Stepps, Valerie Moreno, Mary Beth Herndier, Brian G. Lusso, Paolo McCune, Joseph M. J Exp Med Articles 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. The Rockefeller University Press 1999-06-21 /pmc/articles/PMC2192958/ /pubmed/10377191 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Gobbi, Alberto
Stoddart, Cheryl A.
Malnati, Mauro S.
Locatelli, Giuseppe
Santoro, Fabio
Abbey, Nancy W.
Bare, Christopher
Linquist-Stepps, Valerie
Moreno, Mary Beth
Herndier, Brian G.
Lusso, Paolo
McCune, Joseph M.
Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title_full Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title_fullStr Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title_full_unstemmed Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title_short Human Herpesvirus 6 (HHV-6) Causes Severe Thymocyte Depletion in SCID-hu Thy/Liv Mice
title_sort human herpesvirus 6 (hhv-6) causes severe thymocyte depletion in scid-hu thy/liv mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192958/
https://www.ncbi.nlm.nih.gov/pubmed/10377191
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