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Gene Review

ORF 1a/1b  -  replicase

Feline infectious peritonitis virus

 
 
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Disease relevance of TGEVgp1

  • A cysteine proteinase, papain-like proteinase (PL1pro), of the human coronavirus 229E (HCoV) regulates the expression of the replicase polyproteins, pp1a and ppa1ab, by cleavage between Gly111 and Asn112, far upstream of its own catalytic residue Cys1054 [1].
  • Viral replicase gene products suffice for coronavirus discontinuous transcription [2].
  • The replicase polyproteins, pp1a and pp1ab, of porcine Transmissible gastroenteritis virus (TGEV) have been predicted to be cleaved by viral proteases into 16 non-structural proteins (nsp) [3].
  • The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase [4].
 

High impact information on TGEVgp1

  • A point mutation within the replicase gene differentially affects coronavirus genome versus minigenome replication [5].
  • We have used vaccinia virus as a vector to clone a 22.5-kbp cDNA that represents the 5' and 3' ends of the human coronavirus 229E (HCoV 229E) genome, the HCoV 229E replicase gene, and a single reporter gene (coding for green fluorescent protein [GFP]) located downstream of a regulatory element for coronavirus mRNA transcription [2].
  • The availability of coronavirus infectious cDNAs heralds a new era in coronavirus genetics and genomic applications, especially within the replicase proteins whose functions in replication and pathogenesis are virtually unknown [6].
  • The data show that the differential cleavage kinetics of sites within pp1a/pp1ab are a conserved feature of coronavirus main proteases and lead us to predict similar processing kinetics for the replicase polyproteins of all coronaviruses [7].
  • The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames [8].

References

  1. A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold . Herold, J., Siddell, S.G., Gorbalenya, A.E. J. Biol. Chem. (1999) [Pubmed]
  2. Viral replicase gene products suffice for coronavirus discontinuous transcription. Thiel, V., Herold, J., Schelle, B., Siddell, S.G. J. Virol. (2001) [Pubmed]
  3. Identification of protease and ADP-ribose 1''-monophosphatase activities associated with transmissible gastroenteritis virus non-structural protein 3. Putics, A., Gorbalenya, A.E., Ziebuhr, J. J. Gen. Virol. (2006) [Pubmed]
  4. Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules. Enjuanes, L., Sola, I., Izeta, A., Sánchez-Morgado, J.M., González, J.M., Alonso, S., Escors, D., Sánchez, C.M. Adv. Exp. Med. Biol. (1999) [Pubmed]
  5. A point mutation within the replicase gene differentially affects coronavirus genome versus minigenome replication. Galán, C., Enjuanes, L., Almazán, F. J. Virol. (2005) [Pubmed]
  6. Development of mouse hepatitis virus and SARS-CoV infectious cDNA constructs. Baric, R.S., Sims, A.C. Curr. Top. Microbiol. Immunol. (2005) [Pubmed]
  7. Conservation of substrate specificities among coronavirus main proteases. Hegyi, A., Ziebuhr, J. J. Gen. Virol. (2002) [Pubmed]
  8. Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling. Yap, Y.L., Zhang, X.W., Danchin, A. BMC Bioinformatics (2003) [Pubmed]
 
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