IL-32: a host proinflammatory factor against influenza viral replication is upregulated by aberrant epigenetic modifications during influenza A virus infection.
نویسندگان
چکیده
Our previous studies with clinical data analysis have shown that the proinflammatory factor IL-32 is activated in response to influenza virus infection. However, little is known about how influenza virus induces IL-32 production, and the role of IL-32 in the host immune responses during viral infection remains unclear. In this study, we show that IL-32 production is stimulated by influenza A virus or dsRNA in human PBMCs from healthy volunteers. We demonstrate that the NF-κB and CREB pathways play key roles in the activation of IL-32 production in response to influenza virus infection in A549 human lung epithelial cells. We then show that aberrant epigenetic modifications in the IL32 promoter are important in the transcriptional regulation of IL-32 expression. Interestingly, one CpG demethylation within the CREB binding site increases the binding of CREB to the promoter, which is followed by IL32 transcriptional activation in influenza A virus-infected cells. Overexpression assays combined with RNA interference show that DNA methyltransferases DNMT1 and DNMT3b are critical for IL32 promoter methylation and gene silencing before viral infection. We have demonstrated the anti-influenza virus function of IL-32. Assays for each of the six IL-32 isoforms (α, β, γ, δ, ε, and ζ) during influenza virus infection indicated that all the isoforms have antiviral activity, with different inhibitory rates, and that the effect of IL-32γ is strongest. Our results indicate that the elevated IL-32 levels triggered by influenza virus infection in turn hamper viral replication.
منابع مشابه
Upregulated by Aberrant Epigenetic against Influenza Viral Replication Is IL-32: A Host Proinflammatory Factor
متن کامل
The Potential Effect of Glycyrrhiza Glabra on Early Step of Influenza Virus Replication
Background and Aims: The emergence of drug-resistant influenza viruses has become a serious threat for human and animal populations. Glycyrrhiza glabra (Gg) is a traditional medicine clinically used for the treatment of viral respiratory infection symptoms in most countries. We evaluated the effects of the herb on influenza virus replication in human lung cultured cells (A549) following the det...
متن کاملالقاء مرگ برنامه‌ریزی شده در سلول‌های اپی‌تلیوم تنفسی انسان آلوده شده با ویروس آنفلوانزا
Introduction: Avian influenza viruses are considered as a serious threat to human and animal health. An increase in expression of proinflammatory cytokines and type I IFN genes, as well as host cell death responses contribute to the pathogenesis of influenza infection. Hence, this study aimed to evaluate the growth dynamics of subacute avian influenza virus in human respiratory alveolar epithel...
متن کاملتغییرات ژنتیکی ویروس و فرار از سامانه ایمنی، چالش‌های پیش‌رو علیه آنفلوآنزا: مقاله مروری
The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share mole...
متن کاملNew Anti-Influenza Agents: Targeting the Virus Entry and Genome Transcription
Introduction: The emergence and spread of the pandemic H1N1 influenza virus in 2009 indicates a limitation in the strategy to control the infection, despite a long-established vaccination programme and approved antivirals. Production the proper vaccine against influenza is difficult due to the genetic recombination of virus in the event of pandemic and co-circulation of drug-resistance variants...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 185 9 شماره
صفحات -
تاریخ انتشار 2010