Biology:NSP1

From HandWiki
Short description: Viral nonstructural protein
NSP1
Identifiers
SymbolRota_NS53
PfamPF00981
InterProIPR002148

NSP1, 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]

References

  1. "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. doi:10.1006/viro.1993.1492. PMID 8395125. 
  2. "The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not required for virus replication". Virology 198 (2): 567–76. February 1994. doi:10.1006/viro.1994.1068. PMID 8291239. 
  3. "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. doi:10.1006/viro.1994.1471. PMID 8030275. 
  4. "Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif". Archives of Virology 144 (2): 345–53. 1999. doi:10.1007/s007050050508. PMID 10470258. 
  5. "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. doi:10.1073/pnas.0408376102. PMID 15741273. 
  6. "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. doi:10.1099/vir.0.82255-0. PMID 17251580. 
  7. "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. doi:10.1128/JVI.02498-06. PMID 17301153. 
  8. Sherry, Barbara, ed (January 2009). "Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism". PLoS Pathogens 5 (1): e1000280. doi:10.1371/journal.ppat.1000280. PMID 19180189. 
  9. "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. doi:10.1128/JVI.00225-10. PMID 20392855. 
  10. "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. doi:10.1128/JVI.02479-12. PMID 23221569.