Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3′ to 5′ exonuclease activity essential for immune suppression
Proceedings of the National Academy of Sciences of the United States of America, ISSN: 0027-8424, Vol: 108, Issue: 6, Page: 2396-2401
2011
- 224Citations
- 187Captures
- 2Mentions
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations224
- Citation Indexes223
- 223
- CrossRef196
- Patent Family Citations1
- Patent Families1
- Captures187
- Readers187
- 187
- Mentions2
- Blog Mentions2
- Blog2
Article Description
Lassa fever virus, a member of the family Arenaviridae, is a highly endemic category A pathogen that causes 300,000-500,000 infections per year in Western Africa. The arenaviral nucleoprotein NP has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. Here we present the crystal structure at 1.5 Å of the immunosuppressive C-terminal portion of Lassa virus NP and illustrate that, unexpectedly, its 3D fold closely mimics that of the DEDDh family of exonucleases. Accompanying biochemical experiments illustrate that NP indeed has a previously unknown, bona fide exonuclease activity, with strict specificity for double-stranded RNA substrates. We further demonstrate that this exonuclease activity is essential for the ability of NP to suppress translocation of IFN regulatory factor 3 and block activation of the innate immune system. Thus, the nucleoprotein is a viral exonuclease with anti-immune activity, and this work provides a unique opportunity to combat arenaviral infections.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79952303123&origin=inward; http://dx.doi.org/10.1073/pnas.1016404108; http://www.ncbi.nlm.nih.gov/pubmed/21262835; https://pnas.org/doi/full/10.1073/pnas.1016404108; https://dx.doi.org/10.1073/pnas.1016404108; https://www.pnas.org/content/108/6/2396
Proceedings of the National Academy of Sciences
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