nsp1

The “leader protein” nsp1 in the SARS-CoV seems to be a counterpart of the leader protein (nsp1; p28 ) of murine hepatitis virus (MHV). However, sequence identity is too low to permit confident sequence alignment between these two proteins, or assignment of putative function by homology with other proteins. In MHV, nsp1 interacts with p10 and p15 (counterparts of SARS nsp7 and nsp10, respectively;) and arrests the cell cycle of transfected cells in G0/G1 phase . Previous immunolocalization and interaction studies in MHV have also indicated that in vivo, nsp1 may act in concert with numerous other viral proteins – counterparts of SARS nsp2, 5, 8, 9, 12, 13 and sars9a.

SARS-CoV nsp1 has also been recently shown to be a potent inducer of CCL5, CXCL10 and CCL3 expression in human lung epithelial cells via the activation of NF-kappaB.

Residues 13-128 of nsp1 represents a novel alpha/beta-fold formed by a mixed parallel/antiparallel 6-stranded beta-barrel, an alpha-helix covering one opening of the barrel, and a 310-helix alongside the barrel. NMR data indicate that full-length nsp1 has the same globular fold as the truncated nsp1, but with additional flexibly disordered regions that correspond to the N-terminal region (residues 1–12) and the long C-terminal tail (residues 129–179). Interestingly, it has been determined that the C-terminal half of MHV nsp1 is dispensable for viral replication in culture but is important for efficient proteolytic cleavage at the nsp1-nsp2 peptide linkage by the papain-like protease and optimal viral replication. Likewise, the long disordered termini of SARS-CoV nsp1 are probably important for the efficient proteolytic processing of this protein from the nascent viral polyprotein chain.

Almeida MS, Johnson MA, Herrmann T, Geralt M, Wuthrich K. Novel {beta}-barrel Fold in the NMR Structure of the Replicase Nonstructural Protein 1 from the SARS Coronavirus. J Virol. 2007 Jan 3 epub.

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Brockway SM, Lu XT, Peters TR, Dermody TS, Denison MR. Intracellular localization and protein interactions of the gene 1 protein p28 during mouse hepatitis virus replication. J Virol. 2004 Nov;78(21):11551-62.

Denison MR, Yount B, Brockway SM, Graham RL, Sims AC, Lu X, Baric RS. Cleavage between replicase proteins p28 and p65 of mouse hepatitis virus is not required for virus replication. J Virol. 2004 Jun;78(11):5957-65.

Law AH, Lee DC, Cheung BK, Yim HC, Lau AS. Role for nonstructural protein 1 of severe acute respiratory syndrome coronavirus in chemokine dysregulation. J Virol. 2007 Jan;81(1):416-22. Epub 2006 Oct 11.