Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells
| Autor: | Emanuel F. Petricoin, Serguei G. Popov, Jessica Kidd, Aarthi Narayanan, Kylene Kehn-Hall, Charles L. Bailey, Fatah Kashanchi, Virginia Espina, Michael J. Turell, Lance A. Liotta, Taissia G. Popova |
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| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
Proteomics Proteome Rift Valley Fever p38 mitogen-activated protein kinases Blotting Western Respiratory System HSP27 Heat-Shock Proteins lcsh:Medicine X-Linked Inhibitor of Apoptosis Protein Biology Infectious Diseases/Viral Infections Humans lcsh:Science Child Virology/Effects of Virus Infection on Host Gene Expression Protein kinase B Cells Cultured Multidisciplinary Kinase lcsh:R Epithelial Cells Phosphoproteins Rift Valley fever virus XIAP Cell biology Apoptosis Caspases Host-Pathogen Interactions Phosphorylation lcsh:Q Female Virology/Host Antiviral Responses Signal transduction Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 11, p e13805 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Rift valley fever virus (RVFV) infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK) and downstream transcriptional factors [STAT1 (Y701), ATF2 (T69/71), MSK1 (S360) and CREB (S133)]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46) correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473), along with phosphorylation of FOX 01/03 (T24/31) which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication. |
| Databáze: | OpenAIRE |
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