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.

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-alpha 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.
AuthorsP Secchiero, P Mirandola, D Zella, C Celeghini, A Gonelli, M Vitale, S Capitani, G Zauli
JournalBlood (Blood) Vol. 98 Issue 8 Pg. 2474-81 (Oct 15 2001) ISSN: 0006-4971 [Print] United States
PMID11588045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD4
  • Antigens, CD95
  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Antigens, CD4 (genetics)
  • Antigens, CD95 (immunology)
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Blotting, Western
  • CD4-Positive T-Lymphocytes (immunology, virology)
  • Cell Line
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation
  • Herpesvirus 7, Human (immunology)
  • Humans
  • Membrane Glycoproteins (genetics, physiology)
  • Recombinant Proteins (metabolism)
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha (genetics, physiology)

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