Faculty Opinions recommendation of Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?

2014 ◽  
Author(s):  
Ivan Gerling
Keyword(s):  
Viral Infection ◽  
Type I ◽  
Type I Ifn ◽  
The Difference

scholarly journals A2.6 Cell-Specific Type I IFN Signatures in Autoimmunity and Viral Infection: What Makes the Difference?

2013 ◽  
Vol 72 (Suppl 1) ◽  
pp. A6.1-A6
Author(s):  
Chieko Kyogoku ◽  
Biljana Smiljanovic ◽  
Joachim R Grün ◽  
Tobias Alexander ◽  
Robert Biesen ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I ◽  
Type I Ifn ◽  
The Difference

scholarly journals Cell-Specific Type I IFN Signatures in Autoimmunity and Viral Infection: What Makes the Difference?

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83776 ◽  
Author(s):  
Chieko Kyogoku ◽  
Biljana Smiljanovic ◽  
Joachim R. Grün ◽  
Robert Biesen ◽  
Ursula Schulte-Wrede ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I ◽  
Type I Ifn ◽  
The Difference

scholarly journals Innate triggering and antiviral effector functions of activin A

2021 ◽  
Author(s):  
Kinda Al-Hourani ◽  
Narayan Ramamurthy ◽  
Emanuele Marchi ◽  
Ruth M Eichinger ◽  
Lian N Lee ◽  
...  
Keyword(s):  
Viral Infection ◽  
Influenza A ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Activin A ◽  
Type I ◽  
Type I Ifn ◽  
Effector Functions

First-line defence against viral infection is contingent upon rapid detection of conserved viral structural and genomic motifs by germline-encoded pattern recognition receptors, followed by activation of the type I IFN system and establishment of an intracellular antiviral state. Novel antiviral functions of bone morphogenetic protein and related activin cytokines, acting in conjunction with, and independently of, type I IFN, have recently been described. Activin A mediates multiple innate and adaptive immune functions, including antiviral effects. However, how such effects are mediated and how activin might be triggered by viral infection have not been defined. Here we addressed this in vivo and in vitro, in humans and mice. Transcriptomic analyses delineated strikingly congruent patterns of gene regulation in hepatocytes stimulated with recombinant activin A and IFNα in vitro. Activin A mRNA, encoded by INHBA, is induced upon activation of RIG-I, MDA5 and TLR7/8 viral nucleic acid sensors in vitro, across multiple cell lines and in human peripheral blood mononuclear cells. In vivo, infection of mice with influenza A also upregulated Inhba mRNA in the lung; this local upregulation of Inhba is retained in MAVS knockout mice, indicating a role for non-RIG-I-like receptors in its induction. Activin induction and signalling were also detectable in patients with chronic viral hepatitis. Together, these data suggest Activin A is triggered in parallel with type I IFN responses and can trigger related antiviral effector functions. This model has implications for the development of targeted antiviral therapies, in addition to revealing novel facets of activin biology.

scholarly journals MHC Class I Molecules Exacerbate Viral Infection by Disrupting Type I Interferon Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Simo Xia ◽  
Yijie Tao ◽  
Likun Cui ◽  
Yizhi Yu ◽  
Sheng Xu
Keyword(s):  
Viral Infection ◽  
Mhc Class I ◽  
Class I ◽  
Type I ◽  
Type I Ifn ◽  
Mhc I ◽  
Cell Responses ◽  
Innate Antiviral Immunity ◽  
Mhc Class I Molecules

MHC class I molecules are key in the presentation of antigen and initiation of adaptive CD8+ T cell responses. In addition to its classical activity, MHC I may possess nonclassical functions. We have previously identified a regulatory role of MHC I in TLR signaling and antibacterial immunity. However, its role in innate antiviral immunity remains unknown. In this study, we found a reduced viral load in MHC I-deficient macrophages that was independent of type I IFN production. Mechanically, MHC I mediated viral suppression by inhibiting the type I IFN signaling pathway, which depends on SHP2. Cross-linking MHC I at the membrane increased SHP2 activation and further suppressed STAT1 phosphorylation. Therefore, our data revealed an inhibitory role of MHC I in type I IFN response to viral infection and expanded our understanding of MHC I and antigen presentation.

scholarly journals miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Jikai Zhang ◽  
Zhijie Li ◽  
Jiapei Huang ◽  
Hang Yin ◽  
Jin Tian ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Antiviral Response ◽  
Innate Immune ◽  
Host Cells ◽  
Type I ◽  
Type I Ifn ◽  
Feline Herpesvirus ◽  
Herpesvirus 1

In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.

scholarly journals Cutting Edge: Fetal/Placental Type I IFN Can Affect Maternal Survival and Fetal Viral Load during Viral Infection

2017 ◽  
Vol 198 (8) ◽  
pp. 3029-3032 ◽  
Author(s):  
Karen Racicot ◽  
Paulomi Aldo ◽  
Ayman El-Guindy ◽  
Ja-Young Kwon ◽  
Roberto Romero ◽  
...  
Keyword(s):  
Viral Load ◽  
Viral Infection ◽  
Cutting Edge ◽  
Type I ◽  
Type I Ifn ◽  
Maternal Survival

scholarly journals African Swine Fever Virus Multigene Family 360 and 530 Genes Affect Host Interferon Response

2004 ◽  
Vol 78 (4) ◽  
pp. 1858-1864 ◽  
Author(s):  
C. L. Afonso ◽  
M. E. Piccone ◽  
K. M. Zaffuto ◽  
J. Neilan ◽  
G. F. Kutish ◽  
...  
Keyword(s):  
Viral Infection ◽  
Multigene Family ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Cdna Clones ◽  
Type I ◽  
Mrna Levels ◽  
Type I Ifn ◽  
Transcriptional Responses

ABSTRACT African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4Δ35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4Δ35 at 3 and 6 h postinfection (hpi). While at 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P < 0.05) mRNA levels in Pr4Δ35-infected macrophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr4Δ35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetratricopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GTP-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression of IFN early-response genes in Pr4Δ35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-α mRNA and secreted IFN-α levels at 3, 8, and 24 hpi revealed undetectable IFN-α in mock- and Pr4-infected macrophages but significant IFN-α levels at 24 hpi in Pr4Δ35-infected macrophages. The absence of IFN-α in Pr4-infected macrophages suggests that MGF360/530 genes either directly or indirectly suppress a type I IFN response. An inability to suppress host type I IFN responses may account for the growth defect of Pr4Δ35 in macrophages and its attenuation in swine.

scholarly journals LncRNAMalat1inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity

2020 ◽  
Vol 117 (38) ◽  
pp. 23695-23706 ◽  
Author(s):  
Wei Liu ◽  
Ziqiao Wang ◽  
Lun Liu ◽  
Zongheng Yang ◽  
Shuo Liu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Negative Regulator ◽  
Type I ◽  
Type I Ifn ◽  
Peripheral Blood Mononuclear ◽  
Interactive Network ◽  
Antiviral Innate Immunity

Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNAMalat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production.Malat1directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degradingRbck1pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency ofMalat1enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reducedMALAT1, augmented IRF3, and increasedIFNAmRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation ofMALAT1in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclearMalat1suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis.

scholarly journals Type I IFN Signaling Is Dispensable during Secondary Viral Infection

2016 ◽  
Vol 12 (8) ◽  
pp. e1005861 ◽  
Author(s):  
Martin P. Hosking ◽  
Claudia T. Flynn ◽  
J. Lindsay Whitton
Keyword(s):  
Viral Infection ◽  
Type I ◽  
Type I Ifn
Sign in / Sign up

Export Citation Format

Share Document