The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

nsP3  - 

Salmon pancreas disease virus

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of nsP3

  • Notable differences between the two viruses include a 24-nucleotide insertion in the C terminus of nsP3 protein of SPDV and amino acid sequence variation at the C termini of the capsid and E1 proteins [1].
  • Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA [2].
  • Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus [3].
  • We found that Ross River virus possesses an in-phase opal termination codon between nsP3 and nsP4, whereas in O'Nyong-nyong virus this termination codon is replaced by an arginine codon [4].
  • The organization of both EEE and WEE virus genomes was like that of other alphaviruses and included a termination codon between the nsP3 and nsP4 genes [5].

High impact information on nsP3

  • Immunoelectron microscopy showed that a portion of Sindbis nsP3 is localized at the nuclear envelope, suggesting a possible site of G3BP recruitment to nsP3-containing complexes [6].
  • These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito [7].
  • Taken together, the results suggest the complex nature of interactions between nsP2, nsP3, the 5' UTR, and host-specific protein factors binding to the 51-nt CSE and involved in RdRp formation [8].
  • Macrodomain mutant ts138 was intermediate, making at 40 degrees C partially phosphorylated P23/nsP3 and reduced amounts of minus strands [3].
  • The most striking phenotype was exhibited by ts4 (Ala268 to Val), which after shift to 40 degrees C made significantly underphosphorylated P23/nsP3 and lost selectively the ability to make minus strands [3].

Chemical compound and disease context of nsP3


Biological context of nsP3

  • The causal mutation was identified as a change of a C to a U residue at nucleotide 4903 in the nsP3 open reading frame that predicted a change of Ala-268 to Val [2].
  • Because neither ts4 nor ts7 complemented 10A complementation group mutants, the genes for nsP2 and nsP3 function initially as a single cistron [2].
  • For some mutants, dramatic differences in nsP3 phosphorylation were noted, both in the level of phosphorylation and in the pattern of electrophoretically distinct forms [10].
  • Thus, although nonessential, the nsP3 nonconserved region may be important for optimal virus replication in diverse host cells [10].
  • In comparison to the consensus sequence of the prototype Egyptian Sindbis strain AR339, S.A.AR86 differed at 5.57% of the nucleotides, including a 54-nucleotide deletion, two insertions of 6 nucleotides each, and a 3-nucleotide insertion in the 3' terminal one-third of the S.A.AR86 nsP3 gene [11].

Associations of nsP3 with chemical compounds

  • We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon [7].
  • Only the C-terminal domain of nsP3 and the E2 glycoprotein showed a higher degree of amino acid substitution than the overall average [12].
  • In two enzootic strains, C-terminal nsP3 domain sequences degenerate into little more than repetitive serine-rich blocks [13].
  • To provide structural proteins for pseudovirion formation, a nonviable mutant construct, pSAG2.3L, which contains a Gly-to-Leu substitution at the - 2 position of the nsP3/4 cleavage site, was used as a helper [14].

Physical interactions of nsP3

  • However, the nsP3 of both ts4 and ts7 allowed reactivation of negative-strand synthesis by stable replication complexes containing nsP4 from ts24 [2].

Other interactions of nsP3

  • Antibodies specific for nsP3, and to a lesser extent antibodies to nsP1, precipitated native replication complexes that retained prelabeled RIs and were active in vitro in viral RNA synthesis [15].

Analytical, diagnostic and therapeutic context of nsP3

  • Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal [7].


  1. Comparison of two aquatic alphaviruses, salmon pancreas disease virus and sleeping disease virus, by using genome sequence analysis, monoclonal reactivity, and cross-infection. Weston, J., Villoing, S., Brémont, M., Castric, J., Pfeffer, M., Jewhurst, V., McLoughlin, M., Rødseth, O., Christie, K.E., Koumans, J., Todd, D. J. Virol. (2002) [Pubmed]
  2. Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA. Wang, Y.F., Sawicki, S.G., Sawicki, D.L. J. Virol. (1994) [Pubmed]
  3. Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus. Dé, I., Fata-Hartley, C., Sawicki, S.G., Sawicki, D.L. J. Virol. (2003) [Pubmed]
  4. Nonstructural proteins nsP3 and nsP4 of Ross River and O'Nyong-nyong viruses: sequence and comparison with those of other alphaviruses. Strauss, E.G., Levinson, R., Rice, C.M., Dalrymple, J., Strauss, J.H. Virology (1988) [Pubmed]
  5. A comparison of the nucleotide sequences of eastern and western equine encephalomyelitis viruses with those of other alphaviruses and related RNA viruses. Weaver, S.C., Hagenbaugh, A., Bellew, L.A., Netesov, S.V., Volchkov, V.E., Chang, G.J., Clarke, D.K., Gousset, L., Scott, T.W., Trent, D.W. Virology (1993) [Pubmed]
  6. Tracking and elucidating alphavirus-host protein interactions. Cristea, I.M., Carroll, J.W., Rout, M.P., Rice, C.M., Chait, B.T., Macdonald, M.R. J. Biol. Chem. (2006) [Pubmed]
  7. Effects of an Opal Termination Codon Preceding the nsP4 Gene Sequence in the O'Nyong-Nyong Virus Genome on Anopheles gambiae Infectivity. Myles, K.M., Kelly, C.L., Ledermann, J.P., Powers, A.M. J. Virol. (2006) [Pubmed]
  8. Changes of the secondary structure of the 5' end of the Sindbis virus genome inhibit virus growth in mosquito cells and lead to accumulation of adaptive mutations. Fayzulin, R., Frolov, I. J. Virol. (2004) [Pubmed]
  9. Sequence of the genome RNA of rubella virus: evidence for genetic rearrangement during togavirus evolution. Dominguez, G., Wang, C.Y., Frey, T.K. Virology (1990) [Pubmed]
  10. Deletion and duplication mutations in the C-terminal nonconserved region of Sindbis virus nsP3: effects on phosphorylation and on virus replication in vertebrate and invertebrate cells. Lastarza, M.W., Grakoui, A., Rice, C.M. Virology (1994) [Pubmed]
  11. Complete nucleotide sequence and full-length cDNA clone of S.A.AR86 a South African alphavirus related to Sindbis. Simpson, D.A., Davis, N.L., Lin, S.C., Russell, D., Johnston, R.E. Virology (1996) [Pubmed]
  12. Structure of the Ockelbo virus genome and its relationship to other Sindbis viruses. Shirako, Y., Niklasson, B., Dalrymple, J.M., Strauss, E.G., Strauss, J.H. Virology (1991) [Pubmed]
  13. Sequencing of prototype viruses in the Venezuelan equine encephalitis antigenic complex. Meissner, J.D., Huang, C.Y., Pfeffer, M., Kinney, R.M. Virus Res. (1999) [Pubmed]
  14. Engineering of a Sagiyama alphavirus RNA-based transient expression vector. Yamaguchi, Y., Shirako, Y. Microbiol. Immunol. (2002) [Pubmed]
  15. Solubilization and immunoprecipitation of alphavirus replication complexes. Barton, D.J., Sawicki, S.G., Sawicki, D.L. J. Virol. (1991) [Pubmed]
WikiGenes - Universities