Cargando…
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,...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782147357787291648 |
---|---|
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. |
format | Text |
id | pubmed-2192958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gobbialberto humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT stoddartcheryla humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT malnatimauros humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT locatelligiuseppe humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT santorofabio humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT abbeynancyw humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT barechristopher humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT linquiststeppsvalerie humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT morenomarybeth humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT herndierbriang humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT lussopaolo humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice AT mccunejosephm humanherpesvirus6hhv6causesseverethymocytedepletioninscidhuthylivmice |