NSP1 (rotavirus) explained

NSP1 (NS53), the product of rotavirus gene 5, is a nonstructural RNA-binding protein that contains a cysteine-rich region and is a component of early replication intermediates. RNA-folding predictions suggest that this region of the NSP1 mRNA can interact with itself, producing a stem-loop structure similar to that found near the 5'-terminus of the NSP1 mRNA.[1]

The carboxyl-half of the rotavirus nonstructural protein NSP1 is not required for virus replication.[2]

NSP1 could play a role in host range restriction.[3]

The cysteine-rich region of NSP1 is not considered essential for genome segment reassortment with heterologous virus.[4]

NSP1 interacts with IRF3 in the infected cell. NSP1 is an antagonist of the IFN-signaling pathway.[5]

Interferon regulatory factor 3 (IRF3) is a key transcription factor involved in the induction of interferon (IFN) in response to viral infection. NSP1 binds to and targets IRF3 for proteasome degradation early post-infection. IRF3 degradation is dependent on the presence of NSP1 and the integrity of the N-terminal zinc-binding domain, coupled with the regulated stability of IRF3 and NSP1 by the proteasome, collectively support the hypothesis that NSP1 is an E3 ubiquitin ligase.[6]

NSP1 could mediates the degradation of IRF3, IRF5, and IRF7 by recognizing a common element of IRF proteins, thereby allowing NSP1 to act as a broad-spectrum antagonist of IRF function.[7]

NSP1 also inhibits activation of NFkappaB[8]

NSP1 inhibits cellular apoptosis by directly interacting p85 subunit of PI3K and thus activating PI3K/Akt survival pathway during early stages of rotavirus infection.[9] [10]

Notes and References

  1. Hua J, Mansell EA, Patton JT . Comparative analysis of the rotavirus NS53 gene: conservation of basic and cysteine-rich regions in the protein and possible stem-loop structures in the RNA . Virology . 196 . 1 . 372–8 . September 1993 . 8395125 . 10.1006/viro.1993.1492. free .
  2. Hua J, Patton JT . The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not required for virus replication . Virology . 198 . 2 . 567–76 . February 1994 . 8291239 . 10.1006/viro.1994.1068. free .
  3. Dunn SJ, Cross TL, Greenberg HB . Comparison of the rotavirus nonstructural protein NSP1 (NS53) from different species by sequence analysis and northern blot hybridization . Virology . 203 . 1 . 178–83 . August 1994 . 8030275 . 10.1006/viro.1994.1471. free .
  4. Okada J, Kobayashi N, Taniguchi K, Urasawa S . Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif . Archives of Virology . 144 . 2 . 345–53 . 1999 . 10470258 . 10.1007/s007050050508. 13288814 .
  5. Barro M, Patton JT . Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3 . Proceedings of the National Academy of Sciences of the United States of America . 102 . 11 . 4114–9 . March 2005 . 15741273 . 554789 . 10.1073/pnas.0408376102. 2005PNAS..102.4114B . free .
  6. Graff JW, Ewen J, Ettayebi K, Hardy ME . Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability . The Journal of General Virology . 88 . Pt 2 . 613–20 . February 2007 . 17251580 . 10.1099/vir.0.82255-0. free .
  7. Barro M, Patton JT . Rotavirus NSP1 Inhibits Expression of Type I Interferon by Antagonizing the Function of Interferon Regulatory Factors IRF3, IRF5, and IRF7 . Journal of Virology . 81 . 9 . 4473–81 . May 2007 . 17301153 . 1900170 . 10.1128/JVI.02498-06.
  8. Graff JW, Ettayebi K, Hardy ME . Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism . PLOS Pathogens . 5 . 1 . e1000280 . January 2009 . 19180189 . 2627925 . 10.1371/journal.ppat.1000280 . Sherry . Barbara . free .
  9. Bagchi P, Dutta D, Chattopadhyay S. Rotavirus Nonstructural Protein 1 Suppresses Virus-Induced Cellular Apoptosis To Facilitate Viral Growth by Activating the Cell Survival Pathways during Early Stages of Infection. Journal of Virology. 84. 13. 6834–6845. July 2010. 20392855. 2903281 . 10.1128/JVI.00225-10 .
  10. Bagchi P, Nandi S, Nayak MK. Molecular Mechanism behind Rotavirus NSP1-Mediated PI3 Kinase Activation: Interaction between NSP1 and the p85 Subunit of PI3 Kinase. Journal of Virology. 87. 4. 2358–2362. February 2013. 23221569. 10.1128/JVI.02479-12. 3571490.

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