Abstract
Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive CD4 +-T-lymphotropic betaherpesvirus that causes severe human thymocyte depletion in heterochimeric SCID-hu thy/liv mice and has been implicated as a potential cofactor in the progression of AIDS. However, the mechanisms of HHV-6-mediated immunosuppression have not yet been fully elucidated. We investigated the phenotypic and functional alterations induced by HHV-6 on peripheral blood-derived human dendritic cells (DC). The infection of DC with HHV-6 A or B was nonproductive, as revealed by calibrated real-time PCR measuring the accumulation of viral genome equivalents over time. Nevertheless, preexposure to HHV-6 markedly impaired the maturation of DC driven by gamma interferon and lipopolysaccharide, as shown by the reduced surface expression of major histocompatibility complex class 1 molecules, HLA-DR, CD40, and CD80. Moreover, HHV-6, but not the closely related betaherpesvirus HHV-7, dramatically suppressed the secretion of interleukin-12 (IL-12) p70 by DC, while the production of other cytokines that influence DC maturation, i.e., IL-10 and tumor necrosis factor alpha, was not significantly modified. Likewise, the secretion of the CC chemokines macrophage inflammatory protein 1β and RANTES was unaltered. Functionally, a pretreatment with HHV-6 impaired the ability of DC to stimulate allogeneic T-cell proliferation. Altogether, these data identify interference with the functional maturation of DC as a potential mechanism of HHV-6-mediated immunosuppression.
| Original language | English |
|---|---|
| Pages (from-to) | 2807-2813 |
| Number of pages | 7 |
| Journal | Journal of Virology |
| Volume | 79 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 2005 |
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ASJC Scopus subject areas
- Immunology
Cite this
Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6. / Smith, Alison P.; Paolucci, Clara; Di Lullo, Giulia; Burastero, Samuele E.; Santoro, Fabio; Lusso, Paolo.
In: Journal of Virology, Vol. 79, No. 5, 03.2005, p. 2807-2813.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6
AU - Smith, Alison P.
AU - Paolucci, Clara
AU - Di Lullo, Giulia
AU - Burastero, Samuele E.
AU - Santoro, Fabio
AU - Lusso, Paolo
PY - 2005/3
Y1 - 2005/3
N2 - Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive CD4 +-T-lymphotropic betaherpesvirus that causes severe human thymocyte depletion in heterochimeric SCID-hu thy/liv mice and has been implicated as a potential cofactor in the progression of AIDS. However, the mechanisms of HHV-6-mediated immunosuppression have not yet been fully elucidated. We investigated the phenotypic and functional alterations induced by HHV-6 on peripheral blood-derived human dendritic cells (DC). The infection of DC with HHV-6 A or B was nonproductive, as revealed by calibrated real-time PCR measuring the accumulation of viral genome equivalents over time. Nevertheless, preexposure to HHV-6 markedly impaired the maturation of DC driven by gamma interferon and lipopolysaccharide, as shown by the reduced surface expression of major histocompatibility complex class 1 molecules, HLA-DR, CD40, and CD80. Moreover, HHV-6, but not the closely related betaherpesvirus HHV-7, dramatically suppressed the secretion of interleukin-12 (IL-12) p70 by DC, while the production of other cytokines that influence DC maturation, i.e., IL-10 and tumor necrosis factor alpha, was not significantly modified. Likewise, the secretion of the CC chemokines macrophage inflammatory protein 1β and RANTES was unaltered. Functionally, a pretreatment with HHV-6 impaired the ability of DC to stimulate allogeneic T-cell proliferation. Altogether, these data identify interference with the functional maturation of DC as a potential mechanism of HHV-6-mediated immunosuppression.
AB - Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive CD4 +-T-lymphotropic betaherpesvirus that causes severe human thymocyte depletion in heterochimeric SCID-hu thy/liv mice and has been implicated as a potential cofactor in the progression of AIDS. However, the mechanisms of HHV-6-mediated immunosuppression have not yet been fully elucidated. We investigated the phenotypic and functional alterations induced by HHV-6 on peripheral blood-derived human dendritic cells (DC). The infection of DC with HHV-6 A or B was nonproductive, as revealed by calibrated real-time PCR measuring the accumulation of viral genome equivalents over time. Nevertheless, preexposure to HHV-6 markedly impaired the maturation of DC driven by gamma interferon and lipopolysaccharide, as shown by the reduced surface expression of major histocompatibility complex class 1 molecules, HLA-DR, CD40, and CD80. Moreover, HHV-6, but not the closely related betaherpesvirus HHV-7, dramatically suppressed the secretion of interleukin-12 (IL-12) p70 by DC, while the production of other cytokines that influence DC maturation, i.e., IL-10 and tumor necrosis factor alpha, was not significantly modified. Likewise, the secretion of the CC chemokines macrophage inflammatory protein 1β and RANTES was unaltered. Functionally, a pretreatment with HHV-6 impaired the ability of DC to stimulate allogeneic T-cell proliferation. Altogether, these data identify interference with the functional maturation of DC as a potential mechanism of HHV-6-mediated immunosuppression.
UR - http://www.scopus.com/inward/record.url?scp=13944254323&partnerID=8YFLogxK
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U2 - 10.1128/JVI.79.5.2807-2813.2005
DO - 10.1128/JVI.79.5.2807-2813.2005
M3 - Article
C2 - 15708999
AN - SCOPUS:13944254323
VL - 79
SP - 2807
EP - 2813
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 5
ER -