Disease relevance of NS1

• Detection of parvovirus B19 NS1-specific antibodies by ELISA and western blotting employing recombinant NS1 protein as antigen [1].
• Nonstructural protein-2 and the replication of canine parvovirus [2].
• Moreover, expression of NS-1 in Sf9 cells caused a change in morphology of the cells and resulted in 10-times-lower titers of recombinant baculovirus during infection, suggesting a cytostatic or cytotoxic action of this protein [3].
• We have previously published a detailed transcription map of Aleutian mink disease parvovirus (ADV) and proposed a model for the translation of the two virion structural proteins (VP1 and VP2) and three nonstructural proteins (NS-1, NS-2, and NS-3) (S. Alexandersen, M. E. Bloom, and S. Perryman, J. Virol. 62:3684-3994, 1988) [3].
• A spliced transcript putatively encoding a truncated version of NS1, as seen with minute virus of mice and adeno-associated virus 2, was also observed [4].

Psychiatry related information on NS1

• A high viral DNA synthesis and maturation was observed in MVMi-infected myeloid cells, but it was undetectable in MVMp infections; moreover, the expression of the cytotoxic nonstructural NS-1 protein, a more reliable parameter of cell permissiveness to MVM infection, was only detected in MVMi-infected cells [5].

High impact information on NS1

• The increase in accumulated R1 relative to R2 in mutant infected or transfected murine cells is independent of RNA stability and transport and decreases, in a polar manner, with the distance of the inserted termination signal from the shared initiation codon for NS1 and NS2 at nucleotide 260 [6].
• We have used Gal4-NS-1 fusion protein constructs to identify and characterize an activating domain encoded within the C-terminal 88 amino acids of NS-1 which competes effectively with the acidic activator domain of the herpes simplex virus VP16 protein [7].
• METHODS: Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1 [8].
• We found that KRV peptide-specific T cells generated in DR-BB rats infected with recombinant vaccinia virus expressing KRV-specific structural and nonstructural proteins could not induce diabetes, indicating that molecular mimicry is not the mechanism by which KRV induces autoimmune diabetes [9].
• Hairpin-primed DNA replication is also observed in the presence of NS1 and the Klenow fragment of the Escherichia coli DNA polymerase I. Addition of ATPgammaS (adenosine 5'-O-(thiotriphosphate)) blocks the initiation of DNA replication but not the extension of pre-existing hairpin primers formed in the presence of NS1 only [10].

Chemical compound and disease context of NS1

• Mutation of lysine 405 to serine in the parvovirus H-1 NS1 abolishes its functions for viral DNA replication, late promoter trans activation, and cytotoxicity [11].
• Cellular components necessary to drive NS1-dependent rolling-circle replication (RCR) were freed from endogenous serine/threonine protein kinases by affinity chromatography, and the eukaryotic DNA polymerases were replaced by the bacteriophage T4 DNA polymerase [12].
• The potential for systemic use of these viruses in targeting metastases might be enhanced if NS1 expression and viral replication could be controlled by an innocuous drug such as tetracycline [13].
• The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3 [14].

Biological context of NS1

• MPV resembled MVM in genome size, replication intermediates, and NS proteins [15].
• The predicted amino acid sequence of the NS proteins of MPV and MVM(i) were nearly identical [15].
• The pathogenesis of infection with minute virus of mice depends on expression of the small nonstructural protein NS2 and on the genotype of the allotropic determinants VP1 and VP2 [16].
• We characterized the large and the small splices of CPV using reverse transcriptase-PCR, NS2 was identified using anti-peptide antibodies against the predicted C-terminal sequence and also by expressing the protein from a plasmid vector [2].
• The transcript for the NS-1 polypeptide was mapped to a block of open reading frame located in the major intron of the left-hand transcription unit in the MVM genome [17].

Anatomical context of NS1

• Synthesis of the NS1 nonstructural protein occurs in permissive and nonpermissive cells, such as megakaryocytes, whereas synthesis of the VP1 and VP2 capsid proteins seems to be restricted to burst-forming units and CFU of erythroid cells [18].
• In (nonpermissive) HeLa cells, the BP44 promoter is not activated by NS-1 [19].
• Cells resembling lymphocytes and macrophages contained both ADV capsid (VP2) and nonstructural (NS1 and NS2) proteins, and were present in a distribution suggestive of infected cells within germinal centres [20].
• For the recombinant line assay, five antigens of human parvovirus B19 that were recombinantly produced in Escherichia coli were applied directly on nitrocellulose membranes: VP2, the aminoterminal and the carboxyterminal domain of VP1 (VP-N and VP-C), VP-1S another fragment of VP-N and NS1 [21].
• Early after infection, NS proteins colocalized with viral DNA to form intranuclear inclusions, whereas VP proteins formed hollow intranuclear shells around the inclusions [22].

Associations of NS1 with chemical compounds

• The ability of the mutant proteins to complement a replication defective NS-1 mutant of the infectious MVM plasmid pMM984 and to activate transcription from the capsid gene promoter in chloramphenicol acetyl transferase expression assays was determined [23].
• NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition [14].
• The serine 405 NS1 protein was translocated normally to the nucleus [11].
• Mutation of the eGFP/NS1 vector to eliminate the nucleoside triphosphate-binding site of NS1 significantly decreased apoptosis, as did treatment of transfected cells with inhibitors of caspase 3 or 9 [24].
• To this end, we performed site-directed mutagenesis, substituting alanine residues for two consensus PKC-phosphorylation sites located within the NS1 C-terminal region, T585 and S588 [25].

Co-localisations of NS1

• The NS-1 protein made in vitro comigrates with VP-1 (MW approximately 83,000), while the NS-2 polypeptide has an apparent molecular weight of 24,000 [17].

Regulatory relationships of NS1

• The parvovirus early protein NS1 positively regulates the expression of the P38 promoter for the viral capsid protein gene [26].

Analytical, diagnostic and therapeutic context of NS1

• Including conformational epitopes in the ELISA increases the diagnostic sensitivity, although immunologically, a temporal (years) attenuation of NS1 antibodies appears to take place [1].
• Spliced messages of the NS1 gene transcripts were detected by RT-PCR [27].
• The large nonstructural protein, NS-1, showed predominantly nuclear localization in Sf9 cells when analyzed by immunofluorescence and had a molecular weight similar to that of wild-type ADV NS-1 [3].
• To search for additional parvovirus variants, we used the new NS1/7.5EC PCR assay whose primers were designed from a conserved region of the B19/V9 sequence and encompasses an MfeI restriction enzyme site that would allow differentiation between B19- and V9-like sequences [28].
• Vaccination studies were performed with partially purified recombinant AMDV VP1/2 capsids as well as with the major AMDV non-structural protein (NS1) [29].

References