Disease relevance of VAULTRC1

• METHODS: AIDS-KS patients were recruited consecutively at the largest AIDS reference hospital in Sao Paulo. Fragments (420 bp) of the VR1 and VR2 regions of KSHV open reading frame (ORF) K1 were amplified by nested PCR and sequenced directly [1].
• Coliphage N4 virion-encapsidated, DNA-dependent RNA polymerase (vRNAP) is inactive on double-stranded N4 DNA; however, denatured promoter-containing templates are accurately transcribed [2].
• Distinct regions of influenza virus PB1 polymerase subunit recognize vRNA and cRNA templates [3].
• In vitro, bacteriophage N4 virion RNA polymerase (vRNAP) recognizes in vivo sites of transcription initiation on single-stranded templates [4].
• Upon transfection into respiratory syncytial virus-infected cells, the synthetic vRNA was "rescued" such that it was amplified, expressed, and packaged into infectious virions [5].

High impact information on VAULTRC1

• In addition, the sequences at both termini of vRNA were fully represented in clone pFV 88, indicating that the cloned DNA contained the complete viral gene coding for the hemagglutinin [6].
• The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept [7].
• Vanilloid receptor 1 (VR1) is expressed by sensory neurons [8].
• N4 vRNAP promoters are comprised of a hairpin structure and conserved sequences [4].
• Competition experiments using the 5' and 3' arms of either the vRNA or cRNA panhandle indicated that the N-terminal binding site is shared by both templates [3].

Chemical compound and disease context of VAULTRC1

• The virus-associated RNA, vRNA, was identified by DNase I treatment of HCMV DNA obtained from sucrose gradient purified virus [9].
• The population was diverse with regard to race and gender (76% Hispanics and blacks, 31% female) and had advanced HIV disease at screening (45% had vRNA >100,000 c/mL, 48% had CD4 cell counts <200 cells/mm3, 20% had a history of Centers for Disease Control class C events) [10].
• The capsaicin receptor vanilloid receptor 1 (TRPV1) (VR1) is a cation channel expressed by sensory neurones and activated by heat, acid pH and ethanol, which may trigger burning pain [11].

Biological context of VAULTRC1

• Analysis of the pattern of nucleotide substitution among alleles at this locus supported the hypothesis that natural selection has acted to enhance amino acid diversity in the two hypervariable regions (VR1 and VR2) of the extracellular portion of the K1 protein [12].
• Coliphage N4 virion RNA polymerase (vRNAP), the most distantly related member of the T7-like family of RNA polymerases, is responsible for transcription of the early genes of the linear double-stranded DNA phage genome [13].
• At week 48, the most common genotype was M184V alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1-2 log,10 below baseline), and M184V with or without TAMs in patients originally assigned to lamivudine/zidovudine [14].
• Mutagenesis of a stem structure within the tRNA(Lys.3). vRNA complex led to disappearance of the +3 pausing event as well as to significantly reduced rates of reverse transcription [15].
• Efficacy of FPV/r QD was maintained in patients with CD4+ cell counts < 50 x 10 cells/l or vRNA >/= 100 000 copies/ml at entry [16].

Anatomical context of VAULTRC1

• Detectable levels of low molecular weight viral RNA (LMW vRNA) were not present in MoMuLV grown in mouse embryo fibroblasts, nor rat cells, nor was it produced by them when they were infected with MoMuLV containing both species of vRNA [17].
• Plasma vRNA levels in these groups were controlled by week 8 and there were no decrease in CD4+ T cells > 50% [18].
• To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist), AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.Experimental approach:Cirrhosis was induced by bile duct ligation [19].
• Sensory fibers containing vanilloid receptor-1 (VR-1) mediate spinal cord stimulation-induced vasodilation [20].
• Using isolated nuclei prepared from influenza virus-infected HeLa cells, factors affecting the synthesis of two species of positive-sense RNA transcripts, i.e., mRNA and cRNA (complementary RNA to vRNA) were analyzed [21].

Associations of VAULTRC1 with chemical compounds

• To develop methods for complementing synthetic vRNA with viral proteins, a cDNA was constructed to encode a vRNA in which all of the viral protein-coding sequences were removed and replaced with a negative-sense copy of the bacterial chloramphenicol acetyltransferase gene [5].
• At week 16, vRNA was > 400 copies/ml in seven of 72 (10% patients receiving abacavir/lamivudine/zidovudine and in 41 of 66 (62%) receiving lamivudine/ zidovudine [14].
• The RNA was centrifuged through sucrose gradients, and R-FeLV virus-specific RNA (vRNA) was located by hybridization of portions of the gradient fractions to R-FeLV complementary DNA. vRNA classes with average sedimentation coefficients of approximately 36S, 28S, 23S, and 15S were identified [22].
• After phenol-chloroform extraction of cytoplasmic fractions from infected cells, poly(A)-containing viral cRNA is found in two forms: in single-stranded RNA and associated with vRNA in partially and fully double-stranded RNA [23].
• The nine plus six base pair panhandle rod of protein-free vRNA is interrupted by a central third element, a single unpaired nucleotide: adenosine 10 or various substitute residues, which appears to cause a bulged conformation in the overall structure [24].

Other interactions of VAULTRC1

• The pattern of diversification of VR1 and VR2 within clades was similar to that between clades, but the immunoreceptor tyrosine-based activation motif (ITAM)-like sequence in the cytoplasmic region of K1 showed strong divergence between clades despite conservation within clades [12].
• Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa protein, termed major vault protein or MVP, and a small vault RNA, vRNA [25].
• The results of DNA probes 21U (VR1-A) and 615U (VR3-B) used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively [26].
• Escherichia coli single-stranded DNA-binding protein (EcoSSB) is required for N4 early transcription in vivo, as well as for in vitro transcription on super-coiled DNA templates containing vRNAP promoters [13].

Analytical, diagnostic and therapeutic context of VAULTRC1

• Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2 [27].
• A three-dimensional structural model of an influenza virus ribonucleoprotein particle reconstituted in vivo from recombinant proteins and a model genomic vRNA has been generated by electron microscopy [28].
• Also, during nine serial passages, the expression of CAT by PIV3-CAT vRNA increased more than 3,000-fold [29].
• CB(1), CB(2) and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.Key results:Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls [19].
• Co-immunoprecipitation was also obtained when the viral transcription-replication system was reconstituted in vivo by transfection of cDNAs and model vRNA template into vaccinia virus-T7-infected cells [30].

References