Disease relevance of N1L

• Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors [1].
• Each of the putative polypeptides has sequence similarity to one or more previously identified poxvirus or cellular proteins, with homology to protein kinases, erythrocyte ankyrin and a vaccinia virus virulence-related protein (ORF N1L) [2].
• Bioinformatic analyses predict that the N1L protein is largely alpha-helical and show that it is conserved in many VV strains, in other orthopoxviruses and in members of other chordopoxvirus genera [3].
• The N1L gene was interrupted by replacing a segment of the ORF with the Escherichia coli beta-galactosidase gene [4].
• The genomic arrangement of MCVI N1L and L1L was equivalent to that of the vaccinia and variola virus homologues [5].

High impact information on N1L

• Compared with other poxvirus virulence factors, the poxvirus N1L protein strongly affects virulence in vivo; however, the precise target of N1L was previously unknown [1].
• These studies define a role for N1L as an immunomodulator of innate immunity by targeting components of NF-kappaB and IRF3 signaling pathways [1].
• The conservation of the N1L protein and the attenuated phenotype of the deletion mutant indicate an important role in the virus life-cycle [3].
• Within this block a secretory protein (ORF N1L) implicated in viral virulence and a functional complement 4b binding protein (ORF C3L) are encoded [6].
• When two-dimensional polyacrylamide gel electrophoretic patterns of [35S]methionine-labeled proteins secreted from cells infected with parental and recombinant viruses were compared, a spot missing from the latter corresponded in molecular weigh and isoelectric point with that predicted from the N1L ORF [4].

Biological context of N1L

• One of the major virokines encoded by the N1L open reading frame is the 13.8 kDa protein [7].
• Lack of N1L gene expression results in a significant decrease of vaccinia virus replication in mouse brain [7].

Analytical, diagnostic and therapeutic context of N1L

• A deletion mutant lacking the N1L gene replicated normally in cell culture, but was attenuated in intranasal and intradermal murine models compared to wild-type and revertant controls [3].

References