Phosphoproteome characterization reveals that Sendai virus infection activates mTOR signaling in human epithelial cells

Öhman, Tiina; Söderholm, Sandra; Paidikondala, Maruthibabu; Lietzén, Niina; Matikainen, Sampsa; Nyman, Tuula A.

doi:10.1002/pmic.201400586

Cited by 20 publications

(18 citation statements)

References 53 publications

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“…cDNA microarray analyses on SeV‐infected cells indicated that the NF‐κB signaling pathway, IRF3 signaling pathway and IFN signaling pathway were activated by SeV infection . A phosphoproteomic analysis of SeV‐infected A549 cells highlighted that the mTOR (mechanistic target of rapamycin) signaling pathway plays a role in SeV infection process . Recently, Zhou et al.…”

Section: Discussionmentioning

confidence: 99%

“…cDNA microarray analyses on SeV-infected cells indicated that the NF-B signaling pathway, IRF3 signaling pathway and IFN signaling pathway were activated by SeV infection [14,28,29]. A phosphoproteomic analysis of SeV-infected A549 cells highlighted that the mTOR (mechanistic target of rapamycin) signaling pathway plays a role in SeV infection process [30]. Recently, Zhou et al performed a subcellular quantitative proteomics analysis on peroxisome-associated proteins in SeV-infected Hep G2 cells, and found 311 host proteins that were differentially regulated, among which they identified LGALS3BP and CALU as potential negative regulators of virus-induced IFN-I production [31].…”

Section: Discussionmentioning

confidence: 99%

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Global quantitative proteomic analysis profiles host protein expression in response to Sendai virus infection

et al. 2017

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Sendai virus (SeV) is an enveloped nonsegmented negative-strand RNA virus that belongs to the genus Respirovirus of the Paramyxoviridae family. As a model pathogen, SeV has been extensively studied to define the basic biochemical and molecular biologic properties of the paramyxoviruses. In addition, SeV-infected host cells were widely employed to uncover the mechanism of innate immune response. To identify proteins involved in the SeV infection process or the SeV-induced innate immune response process, system-wide evaluations of SeV-host interactions have been performed. cDNA microarray, siRNA screening and phosphoproteomic analysis suggested that multiple signaling pathways are involved in SeV infection process. Here, to study SeV-host interaction, a global quantitative proteomic analysis was performed on SeV-infected HEK 293T cells. A total of 4699 host proteins were quantified, with 742 proteins being differentially regulated. Bioinformatics analysis indicated that regulated proteins were mainly involved in "interferon type I (IFN-I) signaling pathway" and "defense response to virus," suggesting that these processes play roles in SeV infection. Further RNAi-based functional studies indicated that the regulated proteins, tripartite motif (TRIM24) and TRIM27, affect SeV-induced IFN-I production. Our data provided a comprehensive view of host cell response to SeV and identified host proteins involved in the SeV infection process or the SeV-induced innate immune response process.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Global quantitative proteomic analysis profiles host protein expression in response to Sendai virus infection

et al. 2017

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“…In biomedicine, phosphoproteins are intriguing candidates for therapeutic interventions because the upstream kinases are relatively easy to target selectively with small molecule drugs (6). Previous MS-based phosphoproteome studies have shown major effects on host protein phosphorylation and reorganization of signal-transduction pathways in viral infections such as HIV-1 (7), lytic ␥ herpesvirus infection (8), porcine reproductive and respiratory syndrome virus (9), rift valley virus (10), Sendai virus (11), and human cytomegalovirus (12) infections.…”

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confidence: 99%

Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages

Söderholm

Kainov

Öhman

et al. 2016

Molecular & Cellular Proteomics

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Influenza A viruses cause infections in the human respiratory tract and give rise to annual seasonal outbreaks, as well as more rarely dreaded pandemics. Influenza A viruses become quickly resistant to the virus-directed antiviral treatments, which are the current main treatment options. A promising alternative approach is to target host cell factors that are exploited by influenza viruses. To this end, we characterized the phosphoproteome of influenza A virus infected primary human macrophages to elucidate the intracellular signaling pathways and critical host factors activated upon influenza infection. We identified 1675 phosphoproteins, 4004 phosphopeptides and 4146 nonredundant phosphosites. The phosphorylation of 1113 proteins (66%) was regulated upon infection, highlighting the importance of such global phosphoproteomic profiling in primary cells. Notably, 285 of the identified phosphorylation sites have not been previously described in publicly available phosphorylation databases, despite many published large-scale phosphoproteome studies using human and mouse cell lines. Systematic bioinformatics analysis of the phosphoproteome data indicated that the phosphorylation of proteins involved in the ubiquitin/proteasome pathway (such as TRIM22 and TRIM25) and antiviral responses (such as MAVS) changed in infected macrophages. Proteins known to play roles in small GTPase-, mitogen-activated protein kinase-, and cyclin-dependent kinase- signaling were also regulated by phosphorylation upon infection. In particular, the influenza infection had a major influence on the phosphorylation profiles of a large number of cyclin-dependent kinase substrates. Functional studies using cyclin-dependent kinase inhibitors showed that the cyclin-dependent kinase activity is required for efficient viral replication and for activation of the host antiviral responses. In addition, we show that cyclin-dependent kinase inhibitors protect IAV-infected mice from death. In conclusion, we provide the first comprehensive phosphoproteome characterization of influenza A virus infection in primary human macrophages, and provide evidence that cyclin-dependent kinases represent potential therapeutic targets for more effective treatment of influenza infections.

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“…GO function annotation and enrichment analysis of the target genes according to three categories of biological process, cellular component, and molecular function demonstrated that viral infection might lead to a wide range of regulatory events in host system. Subsequently, KEGG pathway analysis of these putative target genes indicated involvement of Wnt signaling pathway, MAPK signaling pathway, TGF-beta signaling pathway, and mTOR signaling pathway, which have been shown to be important during the infection processes of some other viruses [50–53]. The bioinformatic analysis described above provided a preliminary dataset for additional screening work to characterize the link between specific miRNAs and target genes during host responses to infection of HFMD-associated pathogens.…”

Section: Discussionmentioning

confidence: 99%

Systematic Identification and Bioinformatic Analysis of MicroRNAs in Response to Infections of Coxsackievirus A16 and Enterovirus 71

Zhu

Fan

et al. 2016

BioMed Research International

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Hand, foot, and mouth disease (HFMD), mainly caused by coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) infections, remains a serious public health issue with thousands of newly diagnostic cases each year since 2008 in China. The mechanisms underlying viral infection, however, are elusive to date. In the present study, we systematically investigated the host cellular microRNA (miRNA) expression patterns in response to CVA16 and EV71 infections. Through microarray examination, 27 miRNAs (15 upregulated and 12 downregulated) were found to be coassociated with the replication process of two viruses, while the expression levels of 15 and 5 miRNAs were significantly changed in CVA16- and EV71-infected cells, respectively. A great number of target genes of 27 common differentially expressed miRNAs were predicted by combined use of two computational target prediction algorithms, TargetScan and MiRanda. Comprehensive bioinformatic analysis of target genes in GO categories and KEGG pathways indicated the involvement of diverse biological functions and signaling pathways during viral infection. These results provide an overview of the roles of miRNAs in virus-host interaction, which will contribute to further understanding of HFMD pathological mechanisms.

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Phosphoproteome characterization reveals that Sendai virus infection activates mTOR signaling in human epithelial cells

Cited by 20 publications

References 53 publications

Global quantitative proteomic analysis profiles host protein expression in response to Sendai virus infection

Global quantitative proteomic analysis profiles host protein expression in response to Sendai virus infection

Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages

Systematic Identification and Bioinformatic Analysis of MicroRNAs in Response to Infections of Coxsackievirus A16 and Enterovirus 71

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