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NSP1  -  nonstructural protein 1

Rotavirus C

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Disease relevance of NSP1

  • The human group C rotavirus NSP1 protein sequence is one amino acid longer than the porcine group C equivalent [1].
  • The presence of SSB-like nonstructural proteins in two members of the family Reoviridae suggests a common mechanism of unwinding viral mRNA prior to packaging and subsequent minus-strand RNA synthesis [2].
  • The nonstructural protein, NS2, of bluetongue virus is a nonspecific single- stranded RNA-binding protein that forms large homomultimers and accumulates in viral inclusion bodies of infected cells [3].
  • By using a vaccinia virus expression system in mammalian cells, we found that the yield of NSP1 was 8- and 13-fold lower than the viral proteins VP2 or NSP3, respectively; while in the presence of proteasome inhibitors such difference could be reduced to 2- to 2.5-fold, respectively [4].
  • We have sequenced the genes encoding the inner capsid protein VP6 and the nonstructural proteins NSP1 and NSP4 of the Indian neonatal serotype P8[11]G9 human/bovine reassortant candidate vaccine rotavirus strain 116E [5].

High impact information on NSP1


Chemical compound and disease context of NSP1

  • Deletion mapping of the rotavirus metalloprotein NS53 (NSP1): the conserved cysteine-rich region is essential for virus-specific RNA binding [10].
  • Mutational analysis of cysteine and histidine residues within the conserved N-terminal zinc-binding domain in NSP1 of bovine rotavirus strain B641 abolished IRF3 degradation in transfected cells [11].
  • The susceptibility of NSP1 to proteasome degradation was fully reversed in a dose-dependent manner by transfection with the full complement of 11 molecules of translation-competent rotavirus mRNAs, but this effect was abrogated by the protein synthesis inhibitor cycloheximide [4].
  • The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production [9].
  • Serine protein kinase activity associated with rotavirus phosphoprotein NSP5 [12].

Biological context of NSP1


Anatomical context of NSP1

  • The nonstructural protein NSP2 is a component of rotavirus replication intermediates and accumulates in cytoplasmic inclusions (viroplasms), sites of genome RNA replication and the assembly of subviral particles [16].
  • Above all, NSP1, the product of gene 5, has several interesting features, such as extreme sequence diversity, a highly conserved cysteine-rich region, RNA-binding activity, accumulation on the cytoskeleton, and non-random segregation in reassortment [17].
  • Reduced binding of single-shelled particles to membranes was seen with membranes treated with (i) a monoclonal antibody previously shown to interact with the C terminus of NS28, (ii) proteases known to cleave the C terminus of NS28, and (iii) the Enzymobead reagent [18].
  • When NSP5 was expressed in COS-7 cells in the absence of other viral proteins, it was uniformly distributed in the cytoplasm [19].
  • Direct evidence showing the interaction of NS28 and its nonglycosylated 20,000-Mr precursor expressed in rabbit reticulocyte lysates and single-shelled particles was obtained by cosedimentation of preformed receptor-ligand complexes through sucrose gradients [18].

Associations of NSP1 with chemical compounds

  • Superfusing cells with U-73122, an inhibitor of phospholipase C, ablated the NSP4 response [9].
  • After metabolic labeling of NSP5 with 32Pi, only serine residues were phosphorylated [12].
  • If these asparagine residues are the sites for carbohydrate attachment, this implies that cleavage of the putative signal peptide does not occur during the maturation of this nonstructural glycoprotein [20].
  • Recently, significant in-roads have been made into our understanding of this disease: both viral infection and virally manufactured nonstructural protein (NSP)4 evoke intracellular Ca(2+) ([Ca(2+)]i) mobilization in native and transformed gastrointestinal epithelial cells [21].
  • We used, as antigens in an enzyme-linked immunosorbent assay (ELISA), affinity-purified recombinant NSP4 (residues 85 to 175) from strains SA11, Wa, and RRV (genotypes A, B, and C, respectively) fused to glutathione S-transferase [22].

Physical interactions of NSP1

  • In this study, we show that NSP5 interacts with VP2 in infected cells [23].

Other interactions of NSP1

  • Published data and the interaction demonstrated here suggest a possible role for NSP5 as an adapter between NSP2 and the replication complex VP2-VP1-VP3 in core assembly and RNA encapsidation, modulating the role of NSP2 as a molecular motor involved in the packaging of viral mRNA [23].
  • The data presented showed evidence, for the first time, of an interaction between VP2 and a nonstructural rotavirus protein [23].
  • The main IgG response was directed toward the structural viral proteins VP2, VP4, and VP6 and toward the nonstructural protein NSP2 [24].
  • We measured the levels of gene 5 and gene 6 mRNA and showed that they were not significantly different, and protein analysis indicated no difference in stability of NSP1 compared with VP6 [25].
  • The amino acid sequence homology between PO-13 and mammalian rotaviruses ranged from 76-77% (VP1) to 16-18% (NSP1) [26].

Analytical, diagnostic and therapeutic context of NSP1

  • Co-immunoprecipitation of proteins from rotavirus-infected cells, using hyperimmune sera monospecific for the NS proteins, showed the same interactions for NSP1 as those observed in yeast [27].
  • The critical role of NSP1 in promoting cell-to-cell spread of rotavirus was demonstrated by using gene 5-specific short interfering RNAs in plaque assays [28].
  • Thus, although nonessential, NSP1 probably plays an active role in rotavirus replication in cell culture [14].
  • Gene 5 (NSP1 gene) of T152, which did not hybridize with those of any other strains examined, was characterized by sequence determination [29].
  • Both B641 NSP1 and OSU NSP1 were stabilized in cells or cell-free extracts in the presence of the proteasome inhibitor MG132 and when the zinc-binding domain was disrupted by site-directed mutagenesis [11].


  1. Molecular characterization of human group C rotavirus genes 6, 7 and 9. James, V.L., Lambden, P.R., Deng, Y., Caul, E.O., Clarke, I.N. J. Gen. Virol. (1999) [Pubmed]
  2. Identification and characterization of the helix-destabilizing activity of rotavirus nonstructural protein NSP2. Taraporewala, Z.F., Patton, J.T. J. Virol. (2001) [Pubmed]
  3. Multimers of the bluetongue virus nonstructural protein, NS2, possess nucleotidyl phosphatase activity: similarities between NS2 and rotavirus NSP2. Taraporewala, Z.F., Chen, D., Patton, J.T. Virology (2001) [Pubmed]
  4. Post-translational regulation of rotavirus protein NSP1 expression in mammalian cells. Piña-Vázquez, C., De Nova-Ocampo, M., Guzmán-León, S., Padilla-Noriega, L. Arch. Virol. (2007) [Pubmed]
  5. Sequence analysis demonstrates that VP6, NSP1 and NSP4 genes of Indian neonatal rotavirus strain 116E are of human origin. Cunliffe, N.A., Das, B.K., Ramachandran, M., Bhan, M.K., Glass, R.I., Gentsch, J.R. Virus Genes (1997) [Pubmed]
  6. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Ball, J.M., Tian, P., Zeng, C.Q., Morris, A.P., Estes, M.K. Science (1996) [Pubmed]
  7. Cell-line-induced mutation of the rotavirus genome alters expression of an IRF3-interacting protein. Kearney, K., Chen, D., Taraporewala, Z.F., Vende, P., Hoshino, Y., Tortorici, M.A., Barro, M., Patton, J.T. EMBO J. (2004) [Pubmed]
  8. Processing of the rough endoplasmic reticulum membrane glycoproteins of rotavirus SA11. Kabcenell, A.K., Atkinson, P.H. J. Cell Biol. (1985) [Pubmed]
  9. The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production. Dong, Y., Zeng, C.Q., Ball, J.M., Estes, M.K., Morris, A.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  10. Deletion mapping of the rotavirus metalloprotein NS53 (NSP1): the conserved cysteine-rich region is essential for virus-specific RNA binding. Hua, J., Chen, X., Patton, J.T. J. Virol. (1994) [Pubmed]
  11. Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability. Graff, J.W., Ewen, J., Ettayebi, K., Hardy, M.E. J. Gen. Virol. (2007) [Pubmed]
  12. Serine protein kinase activity associated with rotavirus phosphoprotein NSP5. Blackhall, J., Fuentes, A., Hansen, K., Magnusson, G. J. Virol. (1997) [Pubmed]
  13. Rotavirus replication: plus-sense templates for double-stranded RNA synthesis are made in viroplasms. Silvestri, L.S., Taraporewala, Z.F., Patton, J.T. J. Virol. (2004) [Pubmed]
  14. Effect of intragenic rearrangement and changes in the 3' consensus sequence on NSP1 expression and rotavirus replication. Patton, J.T., Taraporewala, Z., Chen, D., Chizhikov, V., Jones, M., Elhelu, A., Collins, M., Kearney, K., Wagner, M., Hoshino, Y., Gouvea, V. J. Virol. (2001) [Pubmed]
  15. Nondefective rotavirus mutants with an NSP1 gene which has a deletion of 500 nucleotides, including a cysteine-rich zinc finger motif-encoding region (nucleotides 156 to 248), or which has a nonsense codon at nucleotides 153-155. Taniguchi, K., Kojima, K., Urasawa, S. J. Virol. (1996) [Pubmed]
  16. Multimers formed by the rotavirus nonstructural protein NSP2 bind to RNA and have nucleoside triphosphatase activity. Taraporewala, Z., Chen, D., Patton, J.T. J. Virol. (1999) [Pubmed]
  17. Structure and function of rotavirus NSP1. Taniguchi, K., Kojima, K., Kobayashi, N., Urasawa, T., Urasawa, S. Arch. Virol. Suppl. (1996) [Pubmed]
  18. Receptor activity of rotavirus nonstructural glycoprotein NS28. Au, K.S., Chan, W.K., Burns, J.W., Estes, M.K. J. Virol. (1989) [Pubmed]
  19. Analysis of rotavirus nonstructural protein NSP5 phosphorylation. Blackhall, J., Muñoz, M., Fuentes, A., Magnusson, G. J. Virol. (1998) [Pubmed]
  20. Coding assignment and nucleotide sequence of simian rotavirus SA11 gene segment 10: location of glycosylation sites suggests that the signal peptide is not cleaved. Both, G.W., Siegman, L.J., Bellamy, A.R., Atkinson, P.H. J. Virol. (1983) [Pubmed]
  21. Microbes and microbial toxins: paradigms for microbial-mucosal interactions. VIII. Pathological consequences of rotavirus infection and its enterotoxin. Morris, A.P., Estes, M.K. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  22. Evaluation of serum antibody responses against the rotavirus nonstructural protein NSP4 in children after rhesus rotavirus tetravalent vaccination or natural infection. Vizzi, E., Calviño, E., González, R., Pérez-Schael, I., Ciarlet, M., Kang, G., Estes, M.K., Liprandi, F., Ludert, J.E. Clin. Diagn. Lab. Immunol. (2005) [Pubmed]
  23. Rotavirus nonstructural protein NSP5 interacts with major core protein VP2. Berois, M., Sapin, C., Erk, I., Poncet, D., Cohen, J. J. Virol. (2003) [Pubmed]
  24. Viral proteins VP2, VP6, and NSP2 are strongly precipitated by serum and fecal antibodies from children with rotavirus symptomatic infection. Colomina, J., Gil, M.T., Codoñer, P., Buesa, J. J. Med. Virol. (1998) [Pubmed]
  25. Translational regulation of rotavirus gene expression. Mitzel, D.N., Weisend, C.M., White, M.W., Hardy, M.E. J. Gen. Virol. (2003) [Pubmed]
  26. Complete nucleotide sequence of a group A avian rotavirus genome and a comparison with its counterparts of mammalian rotaviruses. Ito, H., Sugiyama, M., Masubuchi, K., Mori, Y., Minamoto, N. Virus Res. (2001) [Pubmed]
  27. In vivo interactions among rotavirus nonstructural proteins. González, R.A., Torres-Vega, M.A., López, S., Arias, C.F. Arch. Virol. (1998) [Pubmed]
  28. Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3. Barro, M., Patton, J.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Serologic and genomic characterization of a G12 human rotavirus in Thailand. Wakuda, M., Nagashima, S., Kobayashi, N., Pongsuwanna, Y., Taniguchi, K. J. Clin. Microbiol. (2003) [Pubmed]
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