Disease relevance of Oas1b

• Expression of the resistant allele of Oas1b in susceptible embryo fibroblasts resulted in partial inhibition of the replication of a flavivirus but not of an alpha togavirus [1].
• A large body of evidence suggests a critical role for the 1b isoform of the mouse Oas gene (Oas1b) in resistance to West Nile virus (WNV) infection in vivo [2].
• This study has revealed a clear segregation between flavivirus resistance conferred by the Flv locus and sensitivity to dopamine-controlled hypothermia conferred by a novel locus, Diht [3].
• Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas [4].
• In Western blot analysis of L1 proteins from different HPV types, antisera to the L1 peptide reacted only with HPV 16, thus identifying an HPV 16 type-specific linear epitope [5].

Psychiatry related information on Oas1b

• Mutations in L1CAM, the gene encoding the transmembrane multifunctional neuronal adhesion molecule L1, are associated with neurodevelopmental disorders including X-linked hydrocephalus and mental retardation [6].

High impact information on Oas1b

• The LINE-1 (L1) retrotransposon, the most important human mobile element, shapes the genome in many ways [7].
• RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut [8].
• A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease [8].
• L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized [8].
• We show here that L1-EGFP can undergo retrotransposition in vivo and produce fluorescence in mouse testis [9].

Chemical compound and disease context of Oas1b

• We have generated a diploid yeast strain that coexpresses the L1 and L2 capsid proteins of both HPV-6b and HPV-16, and we have purified fully assembled VLPs banding in a cesium chloride gradient at the expected density of 1.29-1.3 mg/ml [10].
• The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine [11].
• Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes [12].
• In this work, we used a lactose-inducible system based on the Lactobacillus casei lactose operon promoter (plac) for expression of the HPV-16 L1 protein in L. casei [13].
• HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S-transferase [14].

Biological context of Oas1b

• The antiviral action of Oas1b was essentially restricted to the early stages in virus life cycle [2].
• Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome 5 [15].
• The phenotype of resistance/susceptibility is determined by a major locus, Wnv, mapping to chromosome 5 within the 0.4-cM-wide interval defined by markers D5Mit408 and D5Mit242 [16].
• The observation that WN virus sensitivity of susceptible mice was completely correlated with the occurrence of a point mutation in 2'-5'-OAS L1 suggests that this isoform may play a critical role in WN pathogenesis [16].
• L1 contains an open reading frame coding for a protein that shows 70% conservation at the amino acid level when compared to the protein predicted to be encoded by L3 [17].

Anatomical context of Oas1b

• To investigate the molecular basis for the sensitivity of WNV to the Oas1b antiviral pathway, we established a stable mouse fibroblastic cell clone that up-regulates Oas1b protein expression under the control of the Tet-Off expression system [2].
• We have generated Ba/F3 cell lines expressing a tamoxifen-inducible active FKHR-L1 mutant [FKHR-L1(A3):ER*] [18].
• It is the founder of a neural group of related cell surface receptors that share with L1 a highly conserved cytoplasmic domain that associates with the cytoskeleton [19].
• PCR analysis of human/rodent hybrid cell line DNA samples showed that the polymorphic L1 elements were located on several different chromosomes [20].
• Nasal immunization of mice with human papillomavirus type 16 (HPV-16) virus-like particles or with the HPV-16 L1 gene elicits specific cytotoxic T lymphocytes in vaginal draining lymph nodes [21].

Associations of Oas1b with chemical compounds

• Linkage analysis of mouse strain-dependent coinheritance between flavivirus resistance and greater sensitivity to the hypothermic effect of dopamine was performed using two genetically unrelated flavivirus-susceptible and two highly congenic flavivirus-resistant mouse strains in parallel with C3H.PRI-Flv(r)-and C3H/HeJARC reference strains [3].
• Actinomycin D chase experiments using BPV-1 L1 expression vectors indicated that the element does not destabilize cytoplasmic polyadenylated RNA [4].
• Importantly, ingestion of transgenic L1 potato was associated with activation of an anti-VLP immune response in mice that was qualitatively similar to that induced by VLP parenteral administration, and this response was enhanced significantly by subsequent oral boosting with purified insect cell-derived VLPs [22].
• L1 RNA, but not protein, was detected biochemically in C3 cells [23].
• The method allows efficient one-step purification of L1 fusion protein from crude bacterial lysates on ELISA plates coated with glutathione casein [14].

Other interactions of Oas1b

• The composite genetic map that has been constructed identifies three novel microsatellite loci, D5Mit68, D5Mit159, and D5Mit242, tightly linked to the Flv locus [24].
• Southern analyses of ME12 and ME5/ME8 using L3, L1-specific and L2-specific probes indicate that these genes have a similar organization. cII was transiently and stably transfected into CV-1 cells [17].
• This, together with the previous data produced by our group, locates Flv to a region on mouse Chr 5 carrying segments that are conserved on either human Chr 4, 12, or 7, but present knowledge does not allow precise identification of the syntenic element [24].
• METHODS AND RESULTS: Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-alpha expression [lineage 1 (L1) and lineage 2 (L2)] and littermate controls (LC) were studied [25].
• We now show that the lack of immunogenicity of polynucleotide vaccines based on the L1 gene can be overcome with codon modified L1, which induces strong immune responses, including conformational virus neutralising antibody and delayed type hypersensitivity [26].

Analytical, diagnostic and therapeutic context of Oas1b

• Comparing the cDNA sequences of 2'-5'-OAS L1, L2, and L3 isoforms, between susceptible and resistant strains, we identified a STOP codon in exon 4 of the gene encoding the L1 isoform in susceptible strains that can lead to a truncated form with amputation of one domain, whereas all resistant mice tested so far have a normal copy of this gene [16].
• The new congenic mouse strains, which were created to carry the Flv(r)-like and Flv(mr) alleles on the standardized genetic background of susceptible mice, represent new animal models of flavivirus resistance conferred by these novel resistance alleles [27].
• In protocol 1, cardiac output (CO) and stroke volume (SV) were measured by MRI and thermodilution (TD) in 15 mice (3 L1, 4 L2, 8 LC) [25].
• In animal PV models, vaccination against L1 and/or L2 viral capsid proteins provides an efficient protection against infection, involving virus type-specific neutralizing antibodies [28].
• Prophylactic vaccines based on the use of virus-like particles (VLPs) obtained by auto-assembly of L1 or L1 and L2 proteins produced by recombinant DNA technology are under phase I/II clinical trials for HPV6/11 associated with condylomas and for HPV16, the most frequent oncogenic genotype [28].

References