Article: Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1beta and 18.
The Journal of general virology
2005 Volume 86, Issue Pt 1, Page(s) 185–195
Abstract: ... IL18- and caspase-1-dependent apoptosis in infected primary human macrophages. ... Several NS1 mutant viruses of human influenza A/PR/8/34 (H1N1) virus were tested for their ability ... with the enhanced activity of caspase-1. These results indicated that the NS1 protein, through the function of its N ...
| Abstract | Several NS1 mutant viruses of human influenza A/PR/8/34 (H1N1) virus were tested for their ability to induce pro-inflammatory cytokines in primary human macrophages. The findings revealed a pronounced difference in the virus-induced cytokine pattern, depending on the functionality of the NS1 protein-encoded domains. The PR8/NS1-125 mutant virus, which encodes the first 125 aa of the NS1 protein, thus lacking the C-terminal domains, induced significantly higher amounts of beta interferon, interleukin (IL) 6, tumour necrosis factor alpha and CCL3 (MIP-1alpha) when compared with the A/PR/8/34 wild-type virus. However, this mutant virus was as efficient as wild-type virus in the inhibition of IL1beta and IL18 release from infected macrophages. Another group of viral mutants either lacking or possessing non-functional RNA-binding and dimerization domains induced 10-50 times more biologically active IL1beta and five times more biologically active IL18 than the wild-type or PR8/NS1-125 viruses. The hallmark of infection with this group of mutant viruses was the induction of rapid apoptosis in infected macrophages, which correlated with the enhanced activity of caspase-1. These results indicated that the NS1 protein, through the function of its N-terminal domains, might control caspase-1 activation, thus repressing the maturation of pro-IL1beta-, pro-IL18- and caspase-1-dependent apoptosis in infected primary human macrophages. |
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| MeSH term(s) | Apoptosis/physiology ; Caspase 1/metabolism ; Cytokines/biosynthesis ; Gene Deletion ; Humans ; Influenza A virus/genetics ; Influenza A virus/physiology ; Interleukin-1/biosynthesis ; Interleukin-18/biosynthesis ; Macrophages/enzymology ; Macrophages/immunology ; Macrophages/virology ; Up-Regulation ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/physiology | |||||
| Chemical Substances | Cytokines ; INS1 protein, influenza virus ; Interleukin-1 ; Interleukin-18 ; Viral Nonstructural Proteins ; Caspase 1 (EC 3.4.22.36) | |||||
| Language | English | |||||
| Publishing date | 2005-01 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 219316-4 | |||||
| ISSN | 1465-2099 ; 0022-1317 | |||||
| ISSN (online) | 1465-2099 | |||||
| ISSN | 0022-1317 | |||||
| DOI | 10.1099/vir.0.80422-0 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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