Granzyme B independently of perforin mediates noncytolytic intracellular inactivation of vesicular stomatitis virus

Grace A. Hommel-Berrey, Markian R. Bochan, Angela H. Montel, W. Scott Goebel, Christopher J. Froelich, Zacharie Brahmi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Cytotoxic cells provide a crucial defense against DNA and RNA vital infections. Here we describe an in vitro model to study the fate of vesicular stomatitis virus (VSV) RNA in cells undergoing apoptosis. Using the [3H]uridine release assay, we show that human LAK cells induce the degradation of RNA in infected U937 cells in addition to inhibiting the production of infectious virions. LAK cell-mediated RNA degradation was blocked by the serine protease inhibitor, 3,4-dichloroisocoumarin. Purified human granzyme B but not inactivated granzyme B, granzyme A, or perforin rapidly induced degradation of RNA in VSV-infected U937 cells in a dose- and time-dependent manner without lysing the cells and suppressed vital production. Northern analysis of RNA extracted from infected cells with a VSV full-length cDNA probe confirmed that levels of vital transcripts were reduced by treatment with granzyme B. Nevertheless, the amount of host β- actin mRNA was also reduced in infected cells, suggesting that treatment with granzyme B induced apoptosis. Consistent with this notion, infected cells exposed to granzyme B rapidly developed DNA strand breakage. Taken together, the data suggest that granzyme B in the absence of perforin reduced VSV production by activating a mechanism that degraded viral transcripts in infected U937 cells.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCellular Immunology
Volume180
Issue number1
DOIs
StatePublished - Aug 25 1997

ASJC Scopus subject areas

  • Immunology

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