Disease relevance of IVNS1ABP

• NS1-Binding protein (NS1-BP): a novel human protein that interacts with the influenza A virus nonstructural NS1 protein is relocalized in the nuclei of infected cells [1].
• We have obtained the complete sequence of cloned full-length DNA (NS DNA) derived from influenza virus gene 8, which codes for two unique polypeptides, NS1 and NS2, and the sequence of the NS2 mRNA [2].
• During this period, the substitution rate in the E2/NS1 region (especially in the hypervariable region located in the N-terminus) was significantly higher in patients with acute hepatitis than in patients with chronic hepatitis (P < 0.05) [3].
• The expressed amber and ochre Su+ tRNAs are functional as suppressors as demonstrated by readthrough of the amber codon which terminates the NS1 gene of an influenza virus or the ochre codon which terminates the hexon gene of adenovirus, respectively [4].
• The influenza virus NS2 mRNA is generated through processing by cellular enzymes of a transcript (the NS1 mRNA) of virion RNA segment 8 [5].

Psychiatry related information on IVNS1ABP

• A heteroplasmic mitochondrial DNA 3310 mutation in the ND1 gene in a patient with type 2 diabetes, hypertrophic cardiomyopathy, and mental retardation [6].
• The only significant correlation between RT parameters and BP amplitudes from Cz was negative correlation between dT (difference time between Choice Reaction Time and Simple Reaction Time), on one hand, and NS1 (P = 0.006) and N1 (P = 0.026), on the other [7].

High impact information on IVNS1ABP

• The approximately 340 nucleotide body region of the NS2 mRNA can be translated in the +1 reading frame, and the sequence indicates that NS1 and NS2 overlap by 70 amino acids that are translated from different reading frames [2].
• These effects required the presence of glutamic acid at position 92 of the NS1 molecule [8].
• The past year has been marked by the discovery that the influenza virus NS1 protein belongs to the group of viral proteins that regulate the nuclear export of mRNA [9].
• Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs [10].
• Immunodetection of 6 nuclear DNA-encoded (20, 23, 24, 30, 49, and 51 kDa) and 1 mitochondrial DNA-encoded (ND1) complex I subunits in fibroblast mitochondria revealed 2 distinct patterns [11].

Chemical compound and disease context of IVNS1ABP

• The significance of circulating antibody to hepatitis C virus (HCV) envelope glycoprotein 2 (E2)/nonstructural protein 1 (NS1) glycoprotein was studied in 83 patients with chronic HCV infection diagnosed by polymerase chain reaction (PCR) [12].
• This mutation replaces leucine with methionine in a conserved extramembrane loop of the ND1 gene and was absent in 514 normal controls and in 63 Leber's hereditary optic neuropathy lineages harboring the primary mutations [13].
• After 5-aza-2'-deoxycytidine treatment, increased expression of MDR1 mRNA transcript was found in prostate cancer cell lines (DU145, DuPro, and ND1) [14].
• It therefore appears likely that C1 is a nonstructural protein of influenza C virus similar to the NS1 protein of influenza A and B viruses [15].
• Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein [16].

Biological context of IVNS1ABP

• NS1-BP contains an N-terminal BTB/POZ domain and five kelch-like tandem repeat elements of approximately 50 amino acids [1].
• These observations suggest that rapid substitution of the amino acid sequence in the hypervariable region of the E2/NS1 region may be one of the mechanisms of persistent HCV infection [3].
• Nucleotide sequencing was used to analyze amino acid substitutions in the putative envelope 1 (E1) and envelope 2/nonstructural 1 (E2/NS1) regions of hepatitis C virus (HCV) to clarify a viral mechanism of persistent infection in three patients with acute hepatitis C who developed chronic hepatitis and two patients with chronic hepatitis [3].
• RNA segment 8 of the influenza virus genome is unique in coding for two polypeptides, NS1 (Mr, approximately 25,000) and NS2 (Mr, approximately 11,000) [17].
• We found that the double-stranded RNA-binding domain of NS1, implicated in innate immunity suppression, is both essential and sufficient for RSAR suppression [18].

Anatomical context of IVNS1ABP

• The addition of a truncated NS1-BP mutant protein to a HeLa cell nuclear extract efficiently inhibited pre-mRNA splicing but not spliceosome assembly [1].
• Here we examine the splicing of NS1 mRNA in vitro, using nuclear extracts from HeLa cells [19].
• In the cell nucleus the NS1 protein of influenza A virus inhibits both pre-mRNA splicing and the nuclear export of mRNAs [20].
• In an attempt to characterize the antigens attached to cells of a line established from a human squamous cell carcinoma of the tongue (CAL 27), BALB/c mice were immunized with whole CAL 27 cells; hybridomas were then produced using spleen cells of the animals and cells of an NS1 syngeneic myeloma [21].
• ND1 mRNA expression was strong in melanized substantia nigra neurons but undetectable in nigral glia [22].

Associations of IVNS1ABP with chemical compounds

• The genetic interaction was confirmed by the specific coprecipitation of the NS1 protein from solution by a glutathione S-transferase-NS1-BP fusion protein and glutathione-Sepharose [1].
• With the chimeric precursors that were not detectably spliced, as with NS1 mRNA itself, a low level of a lariat structure containing only intron and not 3' exon sequences was formed [19].
• Peptide mapping experiments indicated that polypeptides NS1 and NS2 do not share methionine- or leucine-containing tryptic peptides [17].
• Substitution of alanine residues for specific amino acids in the adjacent sequence abrogates its inhibitory activity, thereby unmasking the NES and causing the full-length NS1 protein to be localized to the cytoplasm [20].
• We show that in addition to its consensus 5' and 3' splice sites, NS1 mRNA has an intron branch-point adenosine residue that was functional in lariat formation [19].

Analytical, diagnostic and therapeutic context of IVNS1ABP

• To clarify the role of neuronal complex 1 activity in idiopathic Parkinson's disease (IPD), expression of mitochondrial mRNA encoding the ND1 subunit of mitochondrial complex I was examined by semiquantitative in situ hybridization histochemistry in melanized neurons of human substantia nigra in IPD cases and control subjects [22].
• Immunofluorescence analyses showed that the NS1 protein sequences downstream from position 81 are not required for nuclear transport [23].
• Vaccination of Pigs against Swine Influenza Viruses by Using an NS1-Truncated Modified Live-Virus Vaccine [24].
• Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products [25].
• Under a tentative cutoff value (0.122) statistically calculated from NS1 antibody levels of horses in an area where JEV is not endemic, a high level of qualitative agreement (85.3%) was obtained between the ELISA and immunostaining methods [26].

References