scholarly journals Imperative role of particulate matter in innate immunity during RNA virus infection

2020 ◽  
Author(s):  
Richa Mishra ◽  
K Pandikannan ◽  
S Gangamma ◽  
Ashwin Ashok Raut ◽  
Himanshu Kumar
Keyword(s):  
Immune Response ◽  
Air Pollution ◽  
Particulate Matter ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Rna Virus ◽  
Innate Immune ◽  
Virus Infectivity ◽  
Transcriptomic Profile ◽  
H5n1 Influenza

ABSTRACTSensing of pathogens by specialized receptors is the hallmark of the innate immune response. Innate immune response also mounts a defense response against various allergens and pollutants including particulate matter present in the atmosphere. Air pollution has been included as the top threat to global health declared by WHO which aims to cover more than three billion people against health emergencies from 2019-2023. Particulate matter (PM), one of the major components of air pollution, is a significant risk factor for many human diseases and its adverse effects include morbidity and premature deaths throughout the world. Several clinical and epidemiological studies have identified a key link between the PM composition and the prevalence of respiratory and inflammatory disorders. However, the underlying molecular mechanism is not well understood. Here, we investigated the influence of air pollutant, PM10 during RNA virus infections using highly pathogenic avian influenza (HPAI). We thus characterized the transcriptomic profile of lung epithelial cell line, A549 treated with PM10 prior to infection with (HPAI) H5N1 influenza virus, which is known to severely affect the lung and cause respiratory damage. We found that PM10 regulates virus infectivity and enhances overall pathogenic burden in the lung cells. Additionally, the transcriptomic profile highlights the connection of host factors related to various metabolic pathways and immune responses which were dysregulated during virus infection. Overall our findings suggest a strong link between the prevalence of respiratory illness and the air quality.

scholarly journals Mitochondrial Antiviral Signaling Protein Plays a Major Role in Induction of the Fish Innate Immune Response against RNA and DNA Viruses

2009 ◽  
Vol 83 (16) ◽  
pp. 7815-7827 ◽  
Author(s):  
Stéphane Biacchesi ◽  
Monique LeBerre ◽  
Annie Lamoureux ◽  
Yoann Louise ◽  
Emilie Lauret ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Teleost Fish ◽  
Rna Virus ◽  
Innate Immune ◽  
Antiviral Signaling ◽  
Mitochondrial Antiviral Signaling ◽  
Fish Cells ◽  
Mitochondrial Antiviral Signaling Protein

ABSTRACT Viral infection triggers host innate immune responses through cellular sensor molecules which activate multiple signaling cascades that induce the production of interferons (IFN) and other cytokines. The recent identification of mammalian cytoplasmic viral RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and their mitochondrial adaptor, the mitochondrial antiviral signaling protein (MAVS), also called IPS-1, VISA, and Cardif, highlights the significance of these molecules in the induction of IFN. Teleost fish also possess a strong IFN system, but nothing is known concerning the RLRs and their downstream adaptor. In this study, we cloned MAVS cDNAs from several fish species (including salmon and zebrafish) and showed that they were orthologs of mammalian MAVS. We demonstrated that overexpression of these mitochondrial proteins in fish cells led to a constitutive induction of IFN and IFN-stimulated genes (ISGs). MAVS-overexpressing cells were almost fully protected against RNA virus infection, with a strong inhibition of both DNA and RNA virus replication (1,000- and 10,000-fold decreases, respectively). Analyses of MAVS deletion mutants showed that both the N-terminal CARD-like and C-terminal transmembrane domains, but not the central proline-rich region, were indispensable for MAVS signaling function. In addition, we cloned the cDNAs encoding a RIG-I-like molecule from salmonid and cyprinid cell lines. Like the case with MAVS, overexpression of RIG-I CARDs in fish cells led to a strong induction of both IFN and ISGs, conferring on fish cells full protection against RNA virus infection. This report provides the first demonstration that teleost fish possess a functional RLR pathway in which MAVS may play a central role in the induction of the innate immune response.

scholarly journals Control of antiviral innate immune response by protein geranylgeranylation

2019 ◽  
Vol 5 (5) ◽  
pp. eaav7999 ◽  
Author(s):  
Shigao Yang ◽  
Alfred T. Harding ◽  
Catherine Sweeney ◽  
David Miao ◽  
Gregory Swan ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Influenza A ◽  
Rna Virus ◽  
Critical Role ◽  
Innate Immune ◽  
Junction Protein ◽  
Mitochondrial Antiviral Signaling ◽  
Destructive Inflammation

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS’ interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates the recruitment of caspase-8 and cFLIPL to the MAVS signalosome and the subsequent cleavage of Ripk1 that terminates MAVS signaling. Consistently, mice with myeloid deficiency of protein geranylgeranylation showed improved survival upon influenza A virus infection. Our work revealed a critical role of protein geranylgeranylation in regulating antiviral innate immune response.

scholarly journals Mammalian Orthoreovirus Factories Modulate Stress Granule Protein Localization by Interaction with G3BP1

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Promisree Choudhury ◽  
Luke D. Bussiere ◽  
Cathy L. Miller
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Nonstructural Protein ◽  
Innate Immune ◽  
Common Mechanism ◽  
Effector Protein ◽  
Associated Proteins ◽  
Mammalian Orthoreovirus ◽  
Late Stages

ABSTRACT Mammalian orthoreovirus (MRV) infection induces phosphorylation of translation initiation factor eIF2α, which promotes the formation of discrete cytoplasmic inclusions, termed stress granules (SGs). SGs are emerging as a component of the innate immune response to virus infection, and modulation of SG assembly is a common mechanism employed by viruses to counter this antiviral response. We previously showed that MRV infection induces SGs early and then interferes with SG formation as infection proceeds. In this work, we found that SG-associated proteins localized to the periphery of virus-encoded cytoplasmic structures, termed virus factories (VFs), where viral transcription, translation, and replication occur. The localization of SG proteins to VFs was dependent on polysome dissociation and occurred via association of the SG effector protein, Ras-GAP SH3-binding protein 1 (G3BP1), with the MRV nonstructural protein σNS, which localizes to VFs via association with VF nucleating protein, μNS. Deletion analysis of the σNS RNA binding domain and G3BP1 RNA (RRM) and ribosomal (RGG) binding domains showed that σNS association and VF localization phenotypes of G3BP1 do not occur solely through RNA or ribosomal binding but require both the RRM and RGG domains of G3BP1 for maximal viral-factory-like structure (VFL) localization and σNS association. Coexpression of σNS and μNS resulted in disruption of normal SG puncta, and in cells lacking G3BP1, MRV replication was enhanced in a manner correlating with strain-dependent induction of host translation shutoff. These results suggest that σNS association with G3BP1 and relocalization of G3BP1 to the VF periphery play roles in SG disruption to facilitate MRV replication in the host translational shutoff environment. IMPORTANCE SGs and SG effector proteins have emerged as important, yet poorly understood, players in the host's innate immune response to virus infection. MRV infection induces SGs early during infection that are dispersed and/or prevented from forming during late stages of infection despite continued activation of the eIF2α signaling pathway. Cellular and viral components involved in disruption of SGs during late stages of MRV infection remain to be elucidated. This work provides evidence that MRV disruption of SGs may be facilitated by association of the MRV nonstructural protein σNS with the major SG effector protein G3BP1 and subsequent localization of G3BP1 and other SG-associated proteins around the peripheries of virus-encoded factories, interrupting the normal formation of SGs. Our findings also reveal the importance of G3BP1 as an inhibitor of MRV replication during infection for the first time.

scholarly journals Innate immune response to encephalomyocarditis virus infection mediated by CD1d

Immunology ◽  
2003 ◽  
Vol 110 (4) ◽  
pp. 519-526 ◽  
Author(s):  
Mark A. Exley ◽  
Nancy J. Bigley ◽  
Olivia Cheng ◽  
Angela Shaulov ◽  
Syed Muhammad Ali Tahir ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Encephalomyocarditis Virus

scholarly journals Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

2016 ◽  
Vol 90 (23) ◽  
pp. 10823-10843 ◽  
Author(s):  
Nicole Arnold ◽  
Thomas Girke ◽  
Suhas Sureshchandra ◽  
Ilhem Messaoudi
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Sensory Ganglia ◽  
Simian Varicella Virus ◽  
Varicella Virus

ABSTRACTPrimary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression.IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection.

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