Parvovirus H-1-induced cell death: influence of intracellular NAD consumption on the regulation of necrosis and apoptosis.
The autonomous parvovirus H-1 exerts tumor-suppressive effects in living organisms and has been shown to specifically interfere with the survival of transformed cells in culture. The mechanism(s) by which H-1 virus induces death of transformed cells is not yet well understood. It has recently been reported that H-1 virus induces apoptotic cell death in the human monocytic U937 cell line, as assessed by biochemical and morphological changes of infected cells (Rayet, B., Lopez-Guerrero, J.-A., Rommelaere, J., Dinsart, C., 1998. Induction of programmed cell death by parvovirus H-1 in U937 cells: connection with the TNFalpha signalling pathway. J. Virol. 72, 8893-8903). Here we show that parvovirus H-1 infection induced early biochemical changes pointing to apoptotic events also in the transformed human keratinocyte cell line, HeLa, and the transformed rat fibroblast cell line, P1. Morphologic changes, however, and in particular the early breakdown of plasma membrane integrity, suggested that apoptosis did not go to completion, leading to necrotic cell death as the major result of parvovirus infection of HeLa and P1 cells. Parvovirus infection of these, and to a significantly lesser extent of U937 cells, was accompanied by rapid depletion of intracellular NAD stores. Inhibition of NAD-consuming enzymes interfered with parvovirus-induced NAD depletion and increased the proportion of H-1 virus-infected cells displaying apoptotic features of cell death. In contrast, a similar prevention of NAD depletion through stimulation of NAD production had little influence on the cell death pathway, suggesting that NAD-consuming enzymes may promote necrosis in a direct way rather than through inducing the overall drop of intracellular NAD.
Ran
Z
Z
Applied Tumor Virology Program, Abt. F0100 and Institut National de la Santé et de la Recherche Médicale U 375, Deutsches Krebsforschungszentrum, 69120, Heidelberg, Germany.
Rayet
B
B
Rommelaere
J
J
Faisst
S
S
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002460:Cell Line; D002472:Cell Transformation, Viral; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology / Q000821:virology; D009243:NAD / Q000378:metabolism* / Q000502:physiology*; D009336:Necrosis; D010322:Parvoviridae Infections / Q000378:metabolism / Q000473:pathology; D017992:Parvovirus / Q000235:genetics*; D051381:Rats; D020298:U937 Cells / Q000201:enzymology / Q000473:pathology / Q000821:virology
D009243:NAD