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 language | English |
|---|---|
| Pages (from-to) | 1953-1960 |
| Number of pages | 8 |
| Journal | Journal of Experimental Medicine |
| Volume | 189 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jun 21 1999 |
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Keywords
- Acquired immunodeficiency syndrome
- Polymerase chain reaction
- T lymphocyte subsets flow cytometry
- Thymus gland
ASJC Scopus subject areas
- Immunology
Cite this
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.
In: Journal of Experimental Medicine, Vol. 189, No. 12, 21.06.1999, p. 1953-1960.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID- hu Thy/Liv mice
AU - Gobbi, Alberto
AU - Stoddart, Cheryl A.
AU - Malnati, Mauro S.
AU - Locatelli, Giuseppe
AU - Santoro, Fabio
AU - Abbey, Nancy W.
AU - Bare, Christopher
AU - Linquist-Stepps, Valerie
AU - Moreno, Mary Beth
AU - Herndier, Brian G.
AU - Lusso, Paolo
AU - McCune, Joseph M.
PY - 1999/6/21
Y1 - 1999/6/21
N2 - 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.
AB - 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.
KW - Acquired immunodeficiency syndrome
KW - Polymerase chain reaction
KW - T lymphocyte subsets flow cytometry
KW - Thymus gland
UR - http://www.scopus.com/inward/record.url?scp=0033591684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033591684&partnerID=8YFLogxK
U2 - 10.1084/jem.189.12.1953
DO - 10.1084/jem.189.12.1953
M3 - Article
VL - 189
SP - 1953
EP - 1960
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 12
ER -