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Essential Role for the dsRNA-Dependent Protein Kinase PKR in Innate Immunity to Viral Infection
Open accessAbstract
The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intranasal infection by the usually innocuous vesicular stomatitis virus, and also display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of eIF2alpha, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prior to the onset of IFN counteraction and the acquired immune response.
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Citations
Cited by
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
Antiviral Actions of Interferons
Samuel, C. E. (2001) · Clinical Microbiology Reviews · doi:10.1128/cmr.14.4.778-809.2001 · Cited by 2,743
mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474
Interferon-inducible antiviral effectors
Sadler, A. J., & Williams, B. R. G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2314 · Cited by 2,160
Metadata
- Authors
- Balachandran, S., Roberts, P. C., Brown, L. E., Truong, H., Pattnaik, A. K., Archer, D. R., & Barber, G. N.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 13
- Issue
- 1
- Pages
- 129-141
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2042433752
- Cited by
- 525
- References
- 0
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Balachandran, S., Roberts, P. C., Brown, L. E., Truong, H., Pattnaik, A. K., Archer, D. R., & Barber, G. N. (2000). Essential Role for the dsRNA-Dependent Protein Kinase PKR in Innate Immunity to Viral Infection. Immunity. https://doi.org/10.1016/s1074-7613(00)00014-5
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.