Giuseppe
Emeritus
J Virol. 2009 Apr 8. [Epub ahead of print]
Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells.
Hsiang TY, Zhao C, Krug RM. - Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712 USA.
The ubiquitin-like ISG15 protein, as well as its conjugating enzymes, are induced by type I interferons (IFNs). Experiments using ISG15-knockout (ISG15-/-) mice established that ISG15 and/or its conjugation inhibits the replication of influenza A virus.
However, in contrast to the virus inhibition results in the mice, the rate of virus replication was similar in ISG15+/+ and ISG15-/- mouse embryo fibroblasts in tissue culture. Here we focus on human tissue culture cells and on the effect of ISG15 and/or its conjugation on influenza A virus gene expression and replication in such cells.
We demonstrate that IFN-induced antiviral activity against influenza A virus in human cells is significantly alleviated by inhibiting ISG15 conjugation using small interfering RNAs (siRNAs) directed against ISG15 conjugating enzymes. IFN-induced antiviral activity against influenza A virus protein synthesis was reduced 5-20 fold by suppressing ISG15 conjugation.
The amounts of the viral proteins that were restored by these siRNA treatments were approximately 40-50% of the amounts produced in cells that were not pretreated with IFN. Further, we show that ISG15 conjugation inhibits influenza A virus replication 10-20-fold at early times after infection in human cells.
These results show that ISG15 conjugation plays a substantial role in the antiviral state induced by IFN in human cells. In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression.
PMID: 19357168 [PubMed - as supplied by publisher]
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Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells.
Hsiang TY, Zhao C, Krug RM. - Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712 USA.
The ubiquitin-like ISG15 protein, as well as its conjugating enzymes, are induced by type I interferons (IFNs). Experiments using ISG15-knockout (ISG15-/-) mice established that ISG15 and/or its conjugation inhibits the replication of influenza A virus.
However, in contrast to the virus inhibition results in the mice, the rate of virus replication was similar in ISG15+/+ and ISG15-/- mouse embryo fibroblasts in tissue culture. Here we focus on human tissue culture cells and on the effect of ISG15 and/or its conjugation on influenza A virus gene expression and replication in such cells.
We demonstrate that IFN-induced antiviral activity against influenza A virus in human cells is significantly alleviated by inhibiting ISG15 conjugation using small interfering RNAs (siRNAs) directed against ISG15 conjugating enzymes. IFN-induced antiviral activity against influenza A virus protein synthesis was reduced 5-20 fold by suppressing ISG15 conjugation.
The amounts of the viral proteins that were restored by these siRNA treatments were approximately 40-50% of the amounts produced in cells that were not pretreated with IFN. Further, we show that ISG15 conjugation inhibits influenza A virus replication 10-20-fold at early times after infection in human cells.
These results show that ISG15 conjugation plays a substantial role in the antiviral state induced by IFN in human cells. In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression.
PMID: 19357168 [PubMed - as supplied by publisher]
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