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iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG.

Yang Y, Liu W, Yan G, Luo Y, Zhao J, Yang X, Mei M, Wu X, Guo X - Front Microbiol (2015)

Bottom Line: Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling.Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner.These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.

ABSTRACT
The rabies virus (RABV) glycoprotein (G) is the principal contributor to the pathogenicity and protective immunity of RABV. In a previous work, we reported that recombinant rabies virus Hep-dG, which was generated by reverse genetics to carry two copies of the G-gene, showed lower virulence than the parental virus rHep-Flury in suckling mice with a better immune protection effect. To better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify and quantify distinct proteins. 10 and 111 differentially expressed proteins were obtained in rHep-Flury and Hep-dG infection groups, respectively. Selected data were validated by western blot and qRT-PCR. Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling. Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner. These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection.

No MeSH data available.


Related in: MedlinePlus

Upstream analyses of differentially expressed proteins in rabies virus Hep-dG infection group. Red, significantly up-regulated proteins; Green, significantly down-regulated proteins; Orange, predicted activation; Blue, predicted inhibition. Lines connecting the molecules indicate molecular relationships. Orange line, lead to activation; Blue line, lead to inhibition; Yellow line, findings inconsistent with state of downstream molecule; Gray line, effect not predicted. More information is available in Table S4 in the Supporting Information.
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Figure 6: Upstream analyses of differentially expressed proteins in rabies virus Hep-dG infection group. Red, significantly up-regulated proteins; Green, significantly down-regulated proteins; Orange, predicted activation; Blue, predicted inhibition. Lines connecting the molecules indicate molecular relationships. Orange line, lead to activation; Blue line, lead to inhibition; Yellow line, findings inconsistent with state of downstream molecule; Gray line, effect not predicted. More information is available in Table S4 in the Supporting Information.

Mentions: To further assess protein alterations detected by iTRAQ, the potential upstream regulators were analyzed. Upstream regulator analysis can predict upstream molecules, which may cause changes in the observed protein expression. The identified upstream regulators were predicted to be activated or inhibited based on activation z-score. Interestingly, based on expression change of multiple interferon-stimulated proteins, 11 upstream regulators were predicted to be activated in Hep-dG infected cells, including IFN Beta, IFNA2, IFNB1, IFNG, IFNL1, IRF3, IRF7, Ifn, Ifnar, Interferon alpha, STAT1, while 2 upstream regulators were predicted to be inhibited, including TRIM24 and ACKR2 (Figure 6, Supporting Information Table S4). In addition, two MHC class I molecules (H2-K and H2-D), which cannot be annotated by IPA software, were significantly up-regulated only in the Hep-dG-infected cells. These results suggested that interferon signaling pathways may be strongly activated in the Hep-dG infection group, but not in rHep-Flury-infected cells.


iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG.

Yang Y, Liu W, Yan G, Luo Y, Zhao J, Yang X, Mei M, Wu X, Guo X - Front Microbiol (2015)

Upstream analyses of differentially expressed proteins in rabies virus Hep-dG infection group. Red, significantly up-regulated proteins; Green, significantly down-regulated proteins; Orange, predicted activation; Blue, predicted inhibition. Lines connecting the molecules indicate molecular relationships. Orange line, lead to activation; Blue line, lead to inhibition; Yellow line, findings inconsistent with state of downstream molecule; Gray line, effect not predicted. More information is available in Table S4 in the Supporting Information.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493837&req=5

Figure 6: Upstream analyses of differentially expressed proteins in rabies virus Hep-dG infection group. Red, significantly up-regulated proteins; Green, significantly down-regulated proteins; Orange, predicted activation; Blue, predicted inhibition. Lines connecting the molecules indicate molecular relationships. Orange line, lead to activation; Blue line, lead to inhibition; Yellow line, findings inconsistent with state of downstream molecule; Gray line, effect not predicted. More information is available in Table S4 in the Supporting Information.
Mentions: To further assess protein alterations detected by iTRAQ, the potential upstream regulators were analyzed. Upstream regulator analysis can predict upstream molecules, which may cause changes in the observed protein expression. The identified upstream regulators were predicted to be activated or inhibited based on activation z-score. Interestingly, based on expression change of multiple interferon-stimulated proteins, 11 upstream regulators were predicted to be activated in Hep-dG infected cells, including IFN Beta, IFNA2, IFNB1, IFNG, IFNL1, IRF3, IRF7, Ifn, Ifnar, Interferon alpha, STAT1, while 2 upstream regulators were predicted to be inhibited, including TRIM24 and ACKR2 (Figure 6, Supporting Information Table S4). In addition, two MHC class I molecules (H2-K and H2-D), which cannot be annotated by IPA software, were significantly up-regulated only in the Hep-dG-infected cells. These results suggested that interferon signaling pathways may be strongly activated in the Hep-dG infection group, but not in rHep-Flury-infected cells.

Bottom Line: Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling.Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner.These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.

ABSTRACT
The rabies virus (RABV) glycoprotein (G) is the principal contributor to the pathogenicity and protective immunity of RABV. In a previous work, we reported that recombinant rabies virus Hep-dG, which was generated by reverse genetics to carry two copies of the G-gene, showed lower virulence than the parental virus rHep-Flury in suckling mice with a better immune protection effect. To better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify and quantify distinct proteins. 10 and 111 differentially expressed proteins were obtained in rHep-Flury and Hep-dG infection groups, respectively. Selected data were validated by western blot and qRT-PCR. Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling. Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner. These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection.

No MeSH data available.


Related in: MedlinePlus