Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4 + T cells

Paola Secchiero, Prisco Mirandola, Davide Zella, Claudio Celeghini, Arianna Gonelli, Marco Vitale, Silvano Capitani, Giorgio Zauli

Research output: Contribution to journalArticle

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Abstract

Human herpesvirus 7 (HHV-7) is endemic in the adult human population. Although HHV-7 preferentially infects activated CD4 + T lymphocytes, the consequence of T-cell infection for viral pathogenesis and immunity are still largely unknown. HHV-7 infection induces apoptosis mostly in uninfected bystander cells but not in productively infected CD4 + T cells. To dissect the underlying molecular events, the role of death-inducing ligands belonging to the tumor necrosis factor (TNF) cytokine superfamily was investigated. HHV-7 selectively up-regulated the expression of TNF-related apoptosis-inducing ligand (TRAIL), but not that of CD95 ligand or TNF-α in lymphoblastoid (SupT1) or primary activated CD4 + T cells. Moreover, in a cell-to-cell-contact assay, HHV-7-infected CD4 + T lymphocytes were cytotoxic for bystander uninfected CD4 + T cells through the TRAIL pathway. By contrast, HHV-7 infection caused a marked decrease of surface TRAIL-R1, but not of TRAIL-R2, CD95, TNF-R1, or TNF-R2. Of note, the down-regulation of TRAIL-R1 selectively occurred in cells coexpressing HHV-7 antigens that became resistant to TRAIL-mediated cytotoxicity. These findings suggest that the TRAIL-mediated induction of T-cell death may represent an important immune evasion mechanism of HHV-7, helping the virus to persist in the host organism throughout its lifetime.

Original languageEnglish
Pages (from-to)2474-2481
Number of pages8
JournalBlood
Volume98
Issue number8
DOIs
Publication statusPublished - Oct 15 2001

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Human Herpesvirus 7
TNF-Related Apoptosis-Inducing Ligand
T-cells
Cell death
Up-Regulation
Tumor Necrosis Factor-alpha
Ligands
Modulation
Apoptosis
T-Lymphocytes
Herpesviridae Infections
Fas Ligand Protein
Immune Evasion
Cytotoxicity
Viruses
Cytotoxic T-Lymphocytes
Virus Diseases
Assays
Immunity
Cell Death

ASJC Scopus subject areas

  • Hematology

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Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4 + T cells. / Secchiero, Paola; Mirandola, Prisco; Zella, Davide; Celeghini, Claudio; Gonelli, Arianna; Vitale, Marco; Capitani, Silvano; Zauli, Giorgio.

In: Blood, Vol. 98, No. 8, 15.10.2001, p. 2474-2481.

Research output: Contribution to journalArticle

Secchiero, Paola ; Mirandola, Prisco ; Zella, Davide ; Celeghini, Claudio ; Gonelli, Arianna ; Vitale, Marco ; Capitani, Silvano ; Zauli, Giorgio. / Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4 + T cells. In: Blood. 2001 ; Vol. 98, No. 8. pp. 2474-2481.
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