Loss of GSH, oxidative stress, and decrease of intracellular pH as sequential steps in viral infection

Maria Rosa Ciriolo, Anna Teresa Palamara, Sandra Incerpi, Emanuela Lafavia, Maria Cristina Buè, Paolo De Vito, Enrico Garaci, Giuseppe Rotilio

Research output: Contribution to journalArticlepeer-review

Abstract

Madin-Darby canine kidney cells infected with Sendai virus rapidly lose GSH without increase in the oxidized products. The reduced tripeptide was quantitatively recovered in the culture medium of the cells. Since the GSH loss in infected cells was not blocked by methionine, a known inhibitor of hepatocyte GSH transport, a nonspecific leakage through the plasma membrane is proposed. UV-irradiated Sendai virus gave the same results, confirming that the major loss of GSH was due to membrane perturbation upon virus fusion. Consequent to the loss of the tripeptide, an intracellular pH decrease occurred, which was due to a reversible impairment of the Na+/H+ antiporter, the main system responsible for maintaining unaltered pH(i) in those cells. At the end of the infection period, a rise in both pH(i) value and GSH content was observed, with a complete recovery in the activity of the antiporter. However, a secondary set up of oxidative stress was observed after 24 h from infection, which is the time necessary for virus budding from cells. In this case, the GSH decrease was partly due to preferential incorporation of the cysteine residue in the viral proteins and partly engaged in mixed disulfides with intracellular proteins. In conclusion, under our conditions of viral infection, oxidative stress is imposed by GSH depletion, occurring in two steps and following direct virus challenge of the cell membrane without the intervention of reactive oxygen species. These results provide a rationale for the reported, and often contradictory, mutual effects of GSH and viral infection.

Original languageEnglish
Pages (from-to)2700-2708
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number5
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Biochemistry

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