@article{mbs:/content/journal/jgv/10.1099/vir.0.80422-0, author = "Stasakova, Jana and Ferko, Boris and Kittel, Christian and Sereinig, Sabine and Romanova, Julia and Katinger, Hermann and Egorov, Andrej", title = "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 1β and 18", journal= "Journal of General Virology", year = "2005", volume = "86", number = "1", pages = "185-195", doi = "https://doi.org/10.1099/vir.0.80422-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.80422-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", 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-1α) 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 IL1β 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 IL1β 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-IL1β-, pro-IL18- and caspase-1-dependent apoptosis in infected primary human macrophages.", }