Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6

Alison P. Smith, Clara Paolucci, Giulia Di Lullo, Samuele E. Burastero, Fabio Santoro, Paolo Lusso

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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 languageEnglish
Pages (from-to)2807-2813
Number of pages7
JournalJournal of Virology
Volume79
Issue number5
DOIs
Publication statusPublished - Mar 2005

Fingerprint

Human herpesvirus 6
Human Herpesvirus 6
interleukin-12
dendritic cells
Interleukin-12
virus replication
Dendritic Cells
immunosuppression
Human herpesvirus 7
Immunosuppression
Human Herpesvirus 7
secretion
Macrophage Inflammatory Proteins
immunosuppressive agents
Chemokine CCL5
CC Chemokines
thymocytes
Viral Genome
major histocompatibility complex
HLA-DR Antigens

ASJC Scopus subject areas

  • Immunology

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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 journalArticle

Smith, Alison P. ; Paolucci, Clara ; Di Lullo, Giulia ; Burastero, Samuele E. ; Santoro, Fabio ; Lusso, Paolo. / Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6. In: Journal of Virology. 2005 ; Vol. 79, No. 5. pp. 2807-2813.
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