PI3K signalling during influenza A virus infections

Hale, Benjamin G.; Randall, Richard E.

doi:10.1042/bst0350186

Cited by 32 publications

(26 citation statements)

References 11 publications

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“…First, we infected different human and murine cells with LCMV and found no evidence for the induction of mitochondrial apoptosis, as assessed by activation of caspases 9 and 3/7, cytochrome c release, and PARP cleavage. Similar to other RNA viruses, including SeV (44,48), influenza virus (49), and JUNV (50), LCMV was found to activate the anti-apoptotic PI3K/Akt pathway early in infection. However, inhibition of PI3K did not accelerate apoptosis in LCMV-infected cells, arguing against a crucial antiapoptotic function of the virus-induced activation of PI3K/Akt.…”

Section: Discussionmentioning

confidence: 70%

Lymphocytic Choriomeningitis Virus Differentially Affects the Virus-Induced Type I Interferon Response and Mitochondrial Apoptosis Mediated by RIG-I/MAVS

Pythoud

Rothenberger

Martínez-Sobrido

et al. 2015

J Virol

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IMPORTANCEArenaviruses are important emerging human pathogens that are maintained in their rodent hosts by persistent infection. Persistent virus is able to subvert the cellular interferon response, a powerful branch of the innate antiviral defense. Here, we investigated the ability of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) to interfere with the induction of programmed cell death, or apoptosis, in response to superinfection with cytopathic RNA viruses. Upon viral challenge, persistent LCMV efficiently blocked induction of interferons, whereas virus-induced apoptosis remained fully active in LCMV-infected cells. Our studies reveal that the persistent virus is able to reshape innate apoptotic signaling in order to prevent interferon production while maintaining programmed cell death as a strategy for innate defense. The differential effect of persistent virus on the interferon response versus its effect on apoptosis appears as a subtle strategy to guarantee sufficiently high viral loads for efficient transmission while maintaining apoptosis as a mechanism of defense.T he arenaviruses are a large family of emerging viruses that includes several causative agents of severe viral hemorrhagic fevers with high mortality in humans (1, 2). Moreover, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) provides a powerful experimental system for the discovery of fundamental concepts of virus-host interaction and viral immunobiology applicable to other pathogens (3, 4). Arenaviruses are enveloped negative-strand RNA viruses whose nonlytic life cycle is restricted to the cytoplasm (1). The viral genome is comprised of two RNA segments that code for two proteins each, using an ambisense coding strategy. The small (S) RNA segment encodes the envelope glycoprotein precursor (GPC) and the nucleoprotein (NP), and the L segment encodes the matrix protein (Z) and the viral polymerase (L).In their natural reservoir hosts, arenaviruses are maintained by persistent infection via vertical transmission from infected mothers to offspring in utero (1). Infection with LCMV of most mouse strains within 24 h of birth, prior to negative selection of T cell and B cell repertoires, results in tolerance and the establishment of a largely asymptomatic carrier state (3). Despite extensive viral replication and high viral loads throughout organs and tissues (5), LCMV carrier mice show only a modest type I interferon (IFN-I) response (6), suggesting that arenaviruses evade or actively suppress, or both, innate immunity (7). Major pathogen recognition receptors (PRRs) implicated in innate detection of arenaviruses in many cell types are the cytosolic RNA helicases (RLHs) retinoic

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Section: Discussionmentioning

confidence: 70%

Lymphocytic Choriomeningitis Virus Differentially Affects the Virus-Induced Type I Interferon Response and Mitochondrial Apoptosis Mediated by RIG-I/MAVS

Pythoud

Rothenberger

Martínez-Sobrido

et al. 2015

J Virol

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“…Thus far, there is no evidence to suggest that Tyr-89 is phosphorylated during virus infection. Thus, it is not clear whether the SH2 binding motif on NS1 mediates the NS1-p85␤ interaction since mutation of Met-93 could potentially destabilize the NS1 dimer (12). Mutation of the p85␤ SH2 domain may help to resolve this question.…”

Section: Discussionmentioning

confidence: 99%

SH3 Binding Motif 1 in Influenza A Virus NS1 Protein Is Essential for PI3K/Akt Signaling Pathway Activation

Shin

Yang

Liu

et al. 2007

J Virol

118

145

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“…Lysates were normalized for protein concentration using a bicinchoninic acid assay (Pierce) and subjected to Western Blot analysis. PI3K activity was assessed through analysis of Akt phosphorylation as previously described (46,47). For these studies, lysates were generated in PhosphoSafe buffer (Chemicon) with an added protease inhibitor mixture (Sigma-Aldrich) and subjected to Western blot analysis.…”

Section: Monolayer Wounding Immunoblot Analysis and Densitometrymentioning

confidence: 99%

Formyl Peptide Receptor-1 Activation Enhances Intestinal Epithelial Cell Restitution through Phosphatidylinositol 3-Kinase-Dependent Activation of Rac1 and Cdc42

Babbin

Jesaitis

Ivanov

et al. 2007

The Journal of Immunology

103

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Inflammatory disorders of the gastrointestinal tract result in the breakdown of the intestinal epithelial barrier in the form of erosion and ulceration. To reestablish the epithelial barrier, the epithelium must efficiently migrate to reseal wounds. Numerous signaling cascades are involved in the induction and regulation of this complex process. N-formyl peptide receptors comprise a group of Gi-coupled receptors that regulate innate immune responses. Previously, we identified the expression of functional N-formyl peptide receptors in model SK-CO15 intestinal epithelial cells and observed a role for activation of these receptors in regulating cellular invasive behavior. In these studies, we performed formyl peptide receptor-1 (FPR) localization and evaluated its role in regulating intestinal epithelial cell wound closure. Immunolocalization studies using a recently developed specific monoclonal anti-FPR Ab demonstrated its localization along the lateral membrane of crypt epithelial cells in normal human colonic epithelium. In vitro studies using the classical FPR agonist fMLF showed that FPR activation significantly enhances model intestinal epithelial cell restitution and that FPR localized along actin filaments in lamellipodial and filopodial extrusions. The increase in cell migration was associated with activation of PI3K, Rac1, and Cdc42. Pharmacologic inhibition of PI3K activity abrogated the fMLF-induced increase in wound closure and activation of both Rac1 and Cdc42. Inhibition of Rac1 and Cdc42 using pharmacologic inhibitors and dominant negative mutants also inhibited the fMLF-induced increase in cell migration. Taken together, theses results support a novel role for FPR stimulation in enhancing intestinal epithelial cell restitution through PI3K-dependent activation of Rac1 and Cdc42.

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PI3K signalling during influenza A virus infections

Cited by 32 publications

References 11 publications

Lymphocytic Choriomeningitis Virus Differentially Affects the Virus-Induced Type I Interferon Response and Mitochondrial Apoptosis Mediated by RIG-I/MAVS

Lymphocytic Choriomeningitis Virus Differentially Affects the Virus-Induced Type I Interferon Response and Mitochondrial Apoptosis Mediated by RIG-I/MAVS

SH3 Binding Motif 1 in Influenza A Virus NS1 Protein Is Essential for PI3K/Akt Signaling Pathway Activation

Formyl Peptide Receptor-1 Activation Enhances Intestinal Epithelial Cell Restitution through Phosphatidylinositol 3-Kinase-Dependent Activation of Rac1 and Cdc42

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