Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helper T (Th) cell antigenic sites were predicted from the primary amino acid sequence (approximately 500 in length) of the envelope (E) glycoprotein (gp) of Japanese encephalitis (JE), West Nile (WN) and Dengue (DEN) I-IV flaviviruses. Prediction of Th epitopes was done by analyzing the occurrence of amphipathic segments, Rothbard-Taylor tetra/pentamer motifs and presence of alpha helix-preferring amino acids. The simultaneous occurrence of all these parameters in segments of E gp were used as criteria for prediction as Th epitopes. Only one cross reactive epitope was predicted in the C-terminal region of the E gp predicted segments of all flaviviruses analyzed. This region is one of the longest amphipathic stretch (approximately from 420 to 455) and also has a fairly large amphipathic score. Based on the predicted findings three selected peptides were synthesized and analyzed for their ability to induce in vitro T cell proliferative response in different inbred strains of mice (Balb/c, C57BL6, C3H/HeJ). Synthetic peptide I and II prepared from C-terminal region gave a cross reactive response to JE, WN and Den-II in Balb/c and C3H/HeJ mice. Synthetic peptide III prepared from N-terminal region gave a proliferative response to DEN-II in Balb/c strain only, indicating differential antigen presentation.
Mol Immunol
PMID:Recognition of helper T cell epitopes in envelope (E) glycoprotein of Japanese encephalitis, west Nile and Dengue viruses. 170 35

A mixed phase hybridization technique was developed to detect dengue virus type 2 (DEN-2) RNA in pools of infected Aedes albopictus mosquitoes using radiolabelled RNA probes. This technique used a guanidine thiocyanate extraction procedure to simplify analyte preparation. The probes contained sequences complementary to portions of the NS-1 or NS-5 genes of the DEN-2 viral genome. One infected mosquito in a pool of 25 could be detected in approximately 48 h. RNAs from DEN serotypes 1-4 were extracted from cultured mosquito (C6/36) cells. The NS-1 RNA probe was highly specific for DEN-2 RNA. The NS-5 RNA probe detected both DEN-2 and DEN-4 RNA. DEN-2 RNA was also detected by molecular hybridization in concentrated solutions of guanidine thiocyanate using the NS-1 probe. Solution hybridization was 10-fold more sensitive when detecting RNA from purified DEN-2 virus than the mixed phase assay and could detect one infected mosquito in a pool of 25 within 6-8 h. Solution hybridizations were performed in 2-3 h vs 16-20 h for mixed phase hybridizations, and solution hybridizations required 5-10 times less mosquito RNA than mixed phase hybridizations to attain comparable sensitivities. However, solution hybridizations did result in a broader probe specificity than mixed phase hybridizations.
Mol Cell Probes 1990 Aug
PMID:Detection of dengue viral RNA in mosquito vectors by mixed phase and solution hybridization. 240 51

We have isolated a cDNA clone after reverse transcription of the genomic RNA of Asibi yellow fever virus whose structure suggests it was formed by self-priming from a 3'-terminal hairpin of 87 nucleotides in the genomic RNA. We have also isolated a clone from cDNA made to Murray Valley encephalitis virus RNA that also appears to have arisen by self-priming from a 3'-terminal structure very similar or identical to that of yellow fever. In addition, 3'-terminal sequencing of the S1 strain of dengue 2 RNA shows that this RNA is also capable of forming a 3'-terminal hairpin of 79 nucleotides. Furthermore, we have identified two 20-nucleotide sequence elements which are present in the 3' untranslated region of all three viruses; one of these sequence elements is repeated in Murray Valley encephalitis and dengue 2 RNA but not in yellow fever RNA. In all three viruses, which represent the three major serological subgroups of the mosquito-borne flaviviruses, the 3'-proximal conserved sequence element, which is found immediately adjacent to the potential 3'-terminal hairpin, is complementary to another conserved domain near the 5' end of the viral RNAs, suggesting that flavivirus RNAs can cyclize (calculated delta G less than -11 kcal; 1 kcal = 4.184 kJ).
J Mol Biol 1987 Nov 05
PMID:Conserved elements in the 3' untranslated region of flavivirus RNAs and potential cyclization sequences. 282 33

The T cell proliferative response to dengue 2 (Jamaica) E-glycoprotein (495 amino acids) was analyzed in vitro using either killed virus or E-protein fragments or synthetic peptides. Inactivated dengue virus stimulated dengue-specific lymph node (LN) CD4+T cell proliferation in BALB/c (H-2d), C3H (H-2k) and DBA/1 (H-2q) but not in C57BL/6 (H-2b) mice. Moreover, LN cells from dengue-virus primed BALB/c mice proliferated in vitro in response to three purified non-overlapping E-protein fragments expressed in E. coli as polypeptides fused to trpE (f22-205, f267-354, f366-424). To further determine T cell epitopes in the E-protein, synthetic peptides were selected using prediction algorithms for T cell epitopes. Highest proliferative responses were obtained after in vitro exposure of virus-primed LN cells to peptides p135-157, p270-298, p295-307 and p337-359. Peptide p59-78 was able to induce specific B and T cell responses in peptide-primed mice of H-2d, H-2q and H-2k haplotypes. Two peptides p59-78 corresponding to two dengue (Jamaica and Sri Lanka) isolates and differing only at position 71 cross-reacted at the B but not at the T cell level in H-2b mice. This analysis of murine T helper cell response to dengue E-protein may be of use in dengue subunit vaccine design.
Mol Immunol 1993 May
PMID:Identification of helper T cell epitopes of dengue virus E-protein. 768 52

Metabolites isolated from marine invertebrates, callipeltin A, crambescidin, ptilomycalin A, celeromycalin, gymnochrome B, gymnochrome D and isogymnochrome D previously shown bioactive on either herpes simplex virus 1 or human immunodeficiency virus, were tested on a new in vitro bioassay using the dengue virus 1. Only gymnochrome D and isogymnochrome D isolated from the living fossil crinoid Gymnocrinus richeri are highly potent dengue antiviral agents.
Cell Mol Life Sci 1998 Feb
PMID:In vitro antiviral activity on dengue virus of marine natural products. 953 59

The tyrosine phosphatase IA-2 is a molecular target of pancreatic islet autoimmunity in type 1 diabetes. T-cell epitope peptides in autoantigens have potential diagnostic and therapeutic applications, and they may hold clues to environmental agents with similar sequences that could trigger or exacerbate autoimmune disease. We identified 13 epitope peptides in IA-2 by measuring peripheral blood T-cell proliferation to 68 overlapping, synthetic peptides encompassing the intracytoplasmic domain of IA-2 in six at-risk type 1 diabetes relatives selected for HLA susceptibility haplotypes. The dominant epitope, VIVMLTPLVEDGVKQC (aa 805-820), which elicited the highest T-cell responses in all at-risk relatives, has 56% identity and 100% similarity over 9 amino acids (aa) with a sequence in VP7, a major immunogenic protein of human rotavirus. Both peptides bind to HLA-DR4(*0401) and are deduced to present identical aa to the T-cell receptor. The contiguous sequence of VP7 has 75% identity and 92% similarity over 12 aa with a known T-cell epitope in glutamic acid decarboxylase (GAD), another autoantigen in type 1 diabetes. This dominant IA-2 epitope peptide also has 75-45% identity and 88-64% similarity over 8-14 aa to sequences in Dengue, cytomegalovirus, measles, hepatitis C, and canine distemper viruses, and the bacterium Haemophilus influenzae. Three other IA-2 epitope peptides are 71-100% similar over 7-12 aa to herpes, rhino-, hanta- and flaviviruses. Two others are 80-82% similar over 10-11 aa to sequences in milk, wheat, and bean proteins. Further studies should now be carried out to directly test the hypothesis that T-cell activation by rotavirus and possibly other viruses, and dietary proteins, could trigger or exacerbate beta-cell autoimmunity through molecular mimicry with IA-2 and (for rotavirus) GAD.
Mol Med 1998 Apr
PMID:T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. 960 76

A split decomposition analysis of dengue (DEN) virus gene sequences revealed extensive networked evolution, indicative of recombination, among DEN-1 strains but not within serotypes DEN-2, DEN-3, or DEN-4. Within DEN-1, two viruses sampled from South America in the last 10 years were identified as recombinants. To map the breakpoints and test their statistical support, we developed a novel maximum likelihood method. In both recombinants, the breakpoints were found to be in similar positions, within the fusion peptide of the envelope protein, demonstrating that a single recombination event occurred prior to the divergence of these two strains. This is the first report of recombination in natural populations of dengue virus.
Mol Biol Evol 1999 Mar
PMID:Phylogenetic evidence for recombination in dengue virus. 1033 Dec 66

Dengue viruses are members of the Flaviviridae and cause dengue fever and the more severe dengue hemorrhagic fever. Although nearly 40 % of the world's population is at risk of dengue infection, there is currently no effective vaccine or chemotherapy for the disease. Processing of the dengue polyprotein into structural and non-structural proteins in a host, which is essential for assembly of infective virions, is carried out by the combined action of host proteases and the trypsin-like, two-component viral NS2B/NS3 serine protease. Although NS2B strongly stimulates the catalytic NS3 protease domain, the latter is fully active against small substrates and possesses detectable activity against larger substrates, making both forms of the enzyme possible targets for drug design. In the crystal structure of a complex of the protease with a Bowman-Birk inhibitor reported here, an Arg residue at the P1 position of the inhibitor is bound in a manner distinctly different from that in other serine proteases of comparable specificity. However, because the regulatory component, NS2B, is not present in the complex, the physiological implications of this observations are currently unclear. The redundant nature of interaction of P1 Arg and Lys residues with Asp129, Tyr150 and Ser163 of the enzyme provides an explanation for the observed behavior of several site-specific mutants of Asp129 in the protease. The strong level of conservation of residues in the protease that interact with the P1 Arg, along with conservation of Arg at P1 of most cleavage sites in other flaviviruses, suggests that observations from this structure are likely to be applicable to many flaviviruses. The structure provides a starting point for design of site-specific mutations to probe the mechanism of catalysis by the catalytic domain, its activation by the regulatory domain and for design of specific inhibitors of enzymatic activity.
J Mol Biol 2000 Aug 25
PMID:Crystal structure of Dengue virus NS3 protease in complex with a Bowman-Birk inhibitor: implications for flaviviral polyprotein processing and drug design. 2035 76

The re-emergence of arboviral diseases such as Dengue Fever and La Crosse encephalitis is primarily due to the failure of insect vector control strategies. The development of a procedure capable of producing stable germ-line transformants in the insect vectors of these diseases would bridge the gap between gene expression systems being developed to curb vector transmission and the identification of important genes and regulatory sequences and their reintroduction back into the insect genome in the form of vector control strategies. The transposable element piggyBac is capable of transposition in a variety of insect species, and could serve as a versatile insect transformation vector. Using plasmid-based excision and transposition assays, we report that this short-ITR transposon undergoes precise, transposase-dependent excision and transposition in embryos of Aedes albopictus and Aedes triseriatus, the vectors of Dengue fever and LaCrosse encephalitis, respectively. These assays allow us easily and rapidly to confirm and assess the potential utility of piggyBac as a gene transfer tool in a given species. piggyBac is an exceptionally mobile and versatile genetic transformation vector, comparable to other transposons currently in use for the transformation of insects. The mobility of the piggyBac element seen in both Ae. albopictus and Ae. triseriatus is further evidence that it can be employed as a germ-line vector in important insect disease vectors.
Mol Genet Genomics 2001 Mar
PMID:Mobility of the piggyBac transposon in embryos of the vectors of Dengue fever (Aedes albopictus) and La Crosse encephalitis (Ae. triseriatus). 1137 Aug 74

Aedes aegypti were injected intrathoracically with double subgenomic Sindbis (dsSIN) viruses with inserted sequences derived from the genome of one or more of the four dengue (DEN) virus serotypes. Mosquitoes were highly resistant to challenge with homologous DEN viruses from which the effector sequences were derived, and resistance to DEN viruses was independent of the orientation of the effector RNA. dsSIN viruses designed to express RNA derived from the premembrane coding region of DEN-2 prevented the accumulation of DEN2 RNA, and C6/36 cells were highly resistant to DEN-2 virus when challenged at 2, 5 or 8 days after the initial dsSIN virus infections, even though the dsSIN-derived RNA had sharply declined at the later time points. Initiation of resistance occurred prior to or within the first 8 h after challenge with DEN-2 virus. We conclude that DEN viruses are inhibited by a mechanism similar to post-transcriptional gene silencing (PTGS) or RNA interference (RNAi) phenomena described in plants and invertebrates, respectively. The potential occurrence of PTGS or RNAi in mosquitoes and mosquito cells suggests new ways of inhibiting the replication of arthropod-borne viruses in mosquito vectors, studying vector-virus interactions, and silencing endogenous mosquito genes.
Insect Mol Biol 2001 Jun
PMID:Sindbis virus-induced silencing of dengue viruses in mosquitoes. 1143 18


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