HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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.

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-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
Topics
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: