Human herpesvirus 7 induces CD4+T-cell death by two distinct mechanisms

Necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells

Paola Secchiero, Louis Flamand, Davide Gibellini, Elisabetta Falcieri, Iole Robuffo, Silvano Capitani, Robert C. Gallo, Giorgio Zauli

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

We have investigated the cytopathic effects induced by the T- lymphotropic human herpesvirus 7 (HHV-7) on the CD4+T-lymphoblastoid SupT1 cell line and primary CD4+T lymphocytes. Acute in vitro HHV-7 infection induced (1) the formation of giant multinucleated syncytia, which eventually underwent necrotic lysis, and (2) single-cell apoptosis. Both cytopathic effects increased with the progression of infection and were blocked by phosphonoformic acid, a specific inhibitor of herpetic DNA polymerase. Using electron microscopy analysis of various samples, we found that all syncytia contained large amounts of virions and that most of them exhibited clear evidence of necrosis, whereas apoptosis was predominantly observed in single cells. Although empty vital capsids could be identified in the cytoplasm of approximately 25% of single cells exhibiting an apoptotic morphology, mature virions were hardly observed in these cells. In both coculture and cell-free HHV-7 infection experiments, a significant correlation was observed between the degree of single-cell apoptosis, evaluated by quantitative flow cytometry after propidium iodide staining, and the decrease in the total number of viable cells. Moreover, in cell-free infection experiments, apoptosis showed a positive correlation also with the viral load, monitored by quantitative HHV-7 DNA polymerase chain reaction. Thus, it appears that apoptosis occurred predominantly in uninfected bystander cells but not in productively HHV-7- infected cells.

Original languageEnglish
Pages (from-to)4502-4512
Number of pages11
JournalBlood
Volume90
Issue number11
Publication statusPublished - Dec 1 1997

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Human Herpesvirus 7
T-cells
Cell death
Cell Death
Apoptosis
T-Lymphocytes
Herpesviridae Infections
Foscarnet
Nucleic Acid Synthesis Inhibitors
Giant Cells
Flow cytometry
Propidium
Polymerase chain reaction
DNA-Directed DNA Polymerase
Virion
Electron microscopy
Experiments
Cells
Capsid
Coculture Techniques

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Secchiero, P., Flamand, L., Gibellini, D., Falcieri, E., Robuffo, I., Capitani, S., ... Zauli, G. (1997). Human herpesvirus 7 induces CD4+T-cell death by two distinct mechanisms: Necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells. Blood, 90(11), 4502-4512.

Human herpesvirus 7 induces CD4+T-cell death by two distinct mechanisms : Necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells. / Secchiero, Paola; Flamand, Louis; Gibellini, Davide; Falcieri, Elisabetta; Robuffo, Iole; Capitani, Silvano; Gallo, Robert C.; Zauli, Giorgio.

In: Blood, Vol. 90, No. 11, 01.12.1997, p. 4502-4512.

Research output: Contribution to journalArticle

Secchiero, P, Flamand, L, Gibellini, D, Falcieri, E, Robuffo, I, Capitani, S, Gallo, RC & Zauli, G 1997, 'Human herpesvirus 7 induces CD4+T-cell death by two distinct mechanisms: Necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells', Blood, vol. 90, no. 11, pp. 4502-4512.
Secchiero, Paola ; Flamand, Louis ; Gibellini, Davide ; Falcieri, Elisabetta ; Robuffo, Iole ; Capitani, Silvano ; Gallo, Robert C. ; Zauli, Giorgio. / Human herpesvirus 7 induces CD4+T-cell death by two distinct mechanisms : Necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells. In: Blood. 1997 ; Vol. 90, No. 11. pp. 4502-4512.
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abstract = "We have investigated the cytopathic effects induced by the T- lymphotropic human herpesvirus 7 (HHV-7) on the CD4+T-lymphoblastoid SupT1 cell line and primary CD4+T lymphocytes. Acute in vitro HHV-7 infection induced (1) the formation of giant multinucleated syncytia, which eventually underwent necrotic lysis, and (2) single-cell apoptosis. Both cytopathic effects increased with the progression of infection and were blocked by phosphonoformic acid, a specific inhibitor of herpetic DNA polymerase. Using electron microscopy analysis of various samples, we found that all syncytia contained large amounts of virions and that most of them exhibited clear evidence of necrosis, whereas apoptosis was predominantly observed in single cells. Although empty vital capsids could be identified in the cytoplasm of approximately 25{\%} of single cells exhibiting an apoptotic morphology, mature virions were hardly observed in these cells. In both coculture and cell-free HHV-7 infection experiments, a significant correlation was observed between the degree of single-cell apoptosis, evaluated by quantitative flow cytometry after propidium iodide staining, and the decrease in the total number of viable cells. Moreover, in cell-free infection experiments, apoptosis showed a positive correlation also with the viral load, monitored by quantitative HHV-7 DNA polymerase chain reaction. Thus, it appears that apoptosis occurred predominantly in uninfected bystander cells but not in productively HHV-7- infected cells.",
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