NSP1 (rotavirus)

NSP1, the product of rotavirus gene 5, is an 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. ↑ Hua J, Mansell EA, Patton JT (September 1993). "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. doi:10.1006/viro.1993.1492. PMID 8395125.
  2. ↑ Hua J, Patton JT (February 1994). "The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not required for virus replication". Virology. 198 (2): 567–76. doi:10.1006/viro.1994.1068. PMID 8291239.
  3. ↑ Dunn SJ, Cross TL, Greenberg HB (August 1994). "Comparison of the rotavirus nonstructural protein NSP1 (NS53) from different species by sequence analysis and northern blot hybridization". Virology. 203 (1): 178–83. doi:10.1006/viro.1994.1471. PMID 8030275.
  4. ↑ Okada J, Kobayashi N, Taniguchi K, Urasawa S (1999). "Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif". Archives of Virology. 144 (2): 345–53. doi:10.1007/s007050050508. PMID 10470258.
  5. ↑ Barro M, Patton JT (March 2005). "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. doi:10.1073/pnas.0408376102. PMC 554789Freely accessible. PMID 15741273.
  6. ↑ Graff JW, Ewen J, Ettayebi K, Hardy ME (February 2007). "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. doi:10.1099/vir.0.82255-0. PMID 17251580.
  7. ↑ Barro M, Patton JT (May 2007). "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. doi:10.1128/JVI.02498-06. PMC 1900170Freely accessible. PMID 17301153.
  8. ↑ Graff JW, Ettayebi K, Hardy ME (January 2009). Sherry B, ed. "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. PMC 2627925Freely accessible. PMID 19180189.
  9. ↑ Bagchi P, Dutta D, Chattopadhyay S (July 2010). "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. doi:10.1128/JVI.00225-10. PMC 2903281Freely accessible. PMID 20392855.
  10. ↑ Bagchi P, Nandi S, Nayak MK (February 2013). "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. doi:10.1128/JVI.02479-12. PMID 23221569.
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