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HCMV-UV and SeV-UV infection of IFNAR KO and wildtype human fibroblasts

ABSTRACT: Type 1 interferon (IFN) plays a critical role in early antiviral defense and priming of adaptive immunity by signalling upregulation of host antiviral interferon-stimulated genes (ISGs). Certain stimuli trigger strong activation of IFN regulatory factor 3 (IRF3) and direct upregulation of ISGs in addition to IFN. It remains unclear why some stimuli are stronger activators of IRF3 and how this leads to IFN-independent antiviral protection. We found that UV-inactivated human cytomegalovirus (HCMV) particles triggered an IFN-independent ISG signature that was absent in cells infected with UV-inactivated Sendai virus (SeV) particles. HCMV particles triggered mostly uniform activation of IRF3 and low-level IFN-? production within the population while SeV particles triggered a small fraction of cells producing abundant IFN-?. These findings suggest that population level activation of IRF3 and antiviral protection emerges from a diversity of responses occurring simultaneously in single cells. Moreover, this occurs in the absence of virus replication.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149705 | GEO | 2020/05/02

REPOSITORIES: GEO

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Exercise Activates Interferon Immune Response of the Liver via Gpld1 to Enhance Antiviral Innate Immunity

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Transcription profiling by array of primary human hepatocytes derived from hepatitis C patients treated with type III interferons (IFNs) for 6 or 24 hours

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2012-03-09 | E-GEOD-31193 | biostudies-arrayexpress

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2017-12-13 | GSE105038 | GEO

The Adenovirus E1A C Terminus Suppresses a Delayed Antiviral Response and Modulates RAS Signaling [IRF3_ChIP]

2017-12-13 | GSE105037 | GEO

Primary human hepatocytes treated with IL28B and the HCV JFH1 Genotype 2A clone.

Project description:Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. Samples were treated with JFHA, and IL28b respectively with three biological replication.

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