Journal article
Respiratory Syncytial Virus Limits α Subunit of Eukaryotic Translation Initiation Factor 2 (eIF2α) Phosphorylation to Maintain Translation and Viral Replication
The Journal of biological chemistry, Vol.285(31), pp.24023-24031
07/30/2010
DOI: 10.1074/jbc.M109.077321
PMCID: PMC2911276
PMID: 20519500
Abstract
The impact of respiratory syncytial virus (RSV) on morbidity and mortality is significant in that it causes bronchiolitis in infants, exacerbations in patients with obstructive lung disease, and pneumonia in immunocompromised hosts. RSV activates protein kinase R (PKR), a cellular kinase relevant to limiting viral replication (Groskreutz, D. J., Monick, M. M., Powers, L. S., Yarovinsky, T. O., Look, D. C., and Hunninghake, G. W. (2006) J. Immunol. 176, 1733–1740). It is activated by autophosphorylation, likely triggered by a double-stranded RNA intermediate during replication of the virus. In most instances, ph-PKR targets the α subunit of eukaryotic translation initiation factor 2 (eIF2α) protein via phosphorylation, leading to an inhibition of translation of cellular and viral protein. However, we found that although ph-PKR increases in RSV infection, significant eIF2α phosphorylation is not observed, and inhibition of protein translation does not occur. RSV infection attenuates eIF2α phosphorylation by favoring phosphatase rather than kinase activity. Although PKR is activated, RSV sequesters PKR away from eIF2α by binding of the kinase to the RSV N protein. This occurs in conjunction with an increase in the association of the phosphatase, PP2A, with eIF2α following PKR activation. The result is limited phosphorylation of eIF2α and continued translation of cellular and viral proteins.
Details
- Title: Subtitle
- Respiratory Syncytial Virus Limits α Subunit of Eukaryotic Translation Initiation Factor 2 (eIF2α) Phosphorylation to Maintain Translation and Viral Replication
- Creators
- Dayna J Groskreutz - Division of Pulmonary, Critical Care, and Occupational Medicine, Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242Ellen C Babor - Division of Pulmonary, Critical Care, and Occupational Medicine, Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242Martha M Monick - Division of Pulmonary, Critical Care, and Occupational Medicine, Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242Steven M Varga - Department of Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Roy J. and Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242Gary W Hunninghake - Division of Pulmonary, Critical Care, and Occupational Medicine, Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(31), pp.24023-24031
- DOI
- 10.1074/jbc.M109.077321
- PMID
- 20519500
- PMCID
- PMC2911276
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 07/30/2010
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Internal Medicine
- Record Identifier
- 9984083886302771
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