Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete genome of mandarin fish Siniperca chuatsi rhabdovirus (SCRV) was cloned and sequenced. It comprises 11,545 nucleotides and contains five genes encoding the nucleoprotein N, the phosphoprotein P, the matrix protein M, the glycoprotein G, and the RNA-dependent RNA polymerase protein L. At the 3' and 5' termini of SCRV genome, leader and trailer sequences show inverse complementarity. The N, P, M and G proteins share the highest sequence identities (ranging from 14.8 to 41.5%) with the respective proteins of rhabdovirus 903/87, the L protein has the highest identity with those of vesiculoviruses, especially with Chandipura virus (44.7%). Phylogenetic analysis of L proteins showed that SCRV clustered with spring vireamia of carp virus (SVCV) and was most closely related to viruses in the genus Vesiculovirus. In addition, an overlapping open reading frame (ORF) predicted to encode a protein similar to vesicular stomatitis virus C protein is present within the P gene of SCRV. Furthermore, an unoverlapping small ORF downstream of M ORF within M gene is predicted (tentatively called orf4). Therefore, the genomic organization of SCRV can be proposed as 3' leader-N-P/C-M-(orf4)-G-L-trailer 5'. Orf4 transcription or translation products could not be detected by northern or Western blot, respectively, though one similar mRNA band to M mRNA was found. This is the first report on one small unoverlapping ORF in M gene of a fish rhabdovirus.
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PMID:Genomic sequence of mandarin fish rhabdovirus with an unusual small non-transcriptional ORF. 1806 57

Beyond common features in their genome organization and replication mechanisms, the evolutionary relationships among viruses of the Rhabdoviridae family are difficult to decipher because of the great variability in the amino acid sequence of their proteins. The phosphoprotein (P) of vesicular stomatitis virus (VSV) is an essential component of the RNA transcription and replication machinery; in particular, it contains binding sites for the RNA-dependent RNA polymerase and for the nucleoprotein. Here, we devised a new method for defining boundaries of structured domains from multiple disorder prediction algorithms, and we identified an autonomous folding C-terminal domain in VSV P (P(CTD)). We show that, like the C-terminal domain of rabies virus (RV) P, VSV P(CTD) binds to the viral nucleocapsid (nucleoprotein-RNA complex). We solved the three-dimensional structure of VSV P(CTD) by NMR spectroscopy and found that the topology of its polypeptide chain resembles that of RV P(CTD). The common part of both proteins could be superimposed with a backbone RMSD from mean atomic coordinates of 2.6 A. VSV P(CTD) has a shorter N-terminal helix (alpha(1)) than RV P(CTD); it lacks two alpha-helices (helices alpha(3) and alpha(6) of RV P), and the loop between strands beta(1) and beta(2) is longer than that in RV. Dynamical properties measured by NMR relaxation revealed the presence of fast motions (below the nanosecond timescale) in loop regions (amino acids 209-214) and slower conformational exchange in the N- and C-terminal helices. Characterization of a longer construct indicated that P(CTD) is preceded by a flexible linker. The results presented here support a modular organization of VSV P, with independent folded domains separated by flexible linkers, which is conserved among different genera of Rhabdoviridae and is similar to that proposed for the P proteins of the Paramyxoviridae.
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PMID:Solution structure of the C-terminal nucleoprotein-RNA binding domain of the vesicular stomatitis virus phosphoprotein. 1865 47

A phosphoprotein (P) is found in all viruses of the Mononegavirales order. These proteins form homo-oligomers, fulfil similar roles in the replication cycles of the various viruses, but differ in their length and oligomerization state. Sequence alignments reveal no sequence similarity among proteins from viruses belonging to the same family. Sequence analysis and experimental data show that phosphoproteins from viruses of the Paramyxoviridae contain structured domains alternating with intrinsically disordered regions. Here, we used predictions of disorder of secondary structure, and an analysis of sequence conservation to predict the domain organization of the phosphoprotein from Sendai virus, vesicular stomatitis virus (VSV) and rabies virus (RV P). We devised a new procedure for combining the results from multiple prediction methods and locating the boundaries between disordered regions and structured domains. To validate the proposed modular organization predicted for RV P and to confirm that the putative structured domains correspond to autonomous folding units, we used two-hybrid and biochemical approaches to characterize the properties of several fragments of RV P. We found that both central and C-terminal domains can fold in isolation, that the central domain is the oligomerization domain, and that the C-terminal domain binds to nucleocapsids. Our results suggest a conserved organization of P proteins in the Rhabdoviridae family in concatenated functional domains resembling that of the P proteins in the Paramyxoviridae family.
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PMID:Modular organization of rabies virus phosphoprotein. 1934 45

The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.
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PMID:Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P. 1957 Oct 6

We wanted to develop a therapeutic approach against rabies disease by targeting the lyssavirus transcription/replication complex. Because this complex (nucleoprotein N-RNA template processed by the L polymerase and its cofactor, the phosphoprotein P) is similar to that of other negative-strand RNA viruses, we aimed to design broad-spectrum antiviral drugs that could be used as a complement to postexposure vaccination and immunotherapy. Recent progress in understanding the structure/function of the rabies virus P, N, and L proteins predicts that the amino-terminal end of P is an excellent target for destabilizing the replication complex because it interacts with both L (for positioning onto the N-RNA template) and N (for keeping N soluble, as needed for viral RNA encapsidation). Thus, peptides mimicking various lengths of the amino-terminal end of P have been evaluated, as follows: (i) for binding properties to the N-P-L partners by the two-hybrid method; (ii) for their capacity to inhibit the transcription/replication of a rabies virus minigenome encoding luciferase in BHK-21-T7 cells; and (iii) for their capacity to inhibit rabies virus infection of BHK-21-T7 cells and of two derivatives of the neuronal SK-N-SH cell line. Peptides P60 and P57 (the first 60 and first 57 NH2 residues of P, respectively) exhibited a rapid, strong, and long-lasting inhibitory potential on luciferase expression (>95% from 24 h to 55 h). P42 was less efficient in its inhibition level (75% for 18 to 30 h) and duration (40% after 48 h). The most promising peptides were synthesized in tandem with the Tat sequence, allowing cell penetration. Their inhibitory effects were observed on BHK-21-T7 cells infected with rabies virus and Lagos bat virus but not with vesicular stomatitis virus. In neuronal cells, a significant inhibition of both nucleocapsid inclusions and rabies virus release was observed.
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PMID:Peptides that mimic the amino-terminal end of the rabies virus phosphoprotein have antiviral activity. 1970 4

The family Rhabdoviridae contains important pathogens of humans, livestock, and crops, including the insect-transmitted vesicular stomatitis virus (VSV) and the neurotropic rabies virus (RV), which is directly transmitted between mammals. In spite of a highly similar organization of RNA genomes, proteins, and virus particles, cell biology of VSV and RV is divergent in several aspects, particularly with respect to their interplay with the cellular host defense. While infection with both rhabdoviruses is recognized via viral triphosphate RNAs by the cytoplasmic RNA helicase/translocase RIG-I, the viral counteractions to limit the response are contrasting. VSV infection is characterized by a rapid general shutdown of host gene expression and severe cytopathic effects, due to multiple activities of the matrix (M) protein affecting host polymerase functions and mRNA nuclear export, and by rapid and high-level virus replication. In contrast, RV spread and transmission relies on preserving the integrity of host cells, particularly of neurons. While a general cell shutdown by RV M is not observed, RV phosphoprotein (P) has developed independent functions to interfere with activation of IRFs and with STAT signaling. The molecular mechanisms employed are different from those of the paramyxovirus P gene products serving similar functions, and illustrate evolution of IFN antagonists to specifically support virus survival in the natural niches.
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PMID:Rhabdovirus evasion of the interferon system. 1971 59

The 2.9-A structure of the vesicular stomatitis virus nucleocapsid (N) protein bound to RNA shows the RNA to be tightly sequestered between the two lobes of the N protein. Domain movement of the lobes of the N protein has been postulated to facilitate polymerase access to the RNA template. We investigated the roles of individual amino acid residues in the C-terminal loop, involved in long-range interactions between N protein monomers, in forming functional ribonucleoprotein (RNP) templates. The effects of specific N protein mutations on its expression, interaction with the phosphoprotein, and formation of RNP templates that supported viral RNA replication and transcription were examined. Mutations introduced into the C-terminal loop, predicted to break contact with other residues in the loop, caused up to 10-fold increases in RNA replication without an equivalent stimulation of transcription. Mutation F348A, predicted to break contact between the C-terminal loop and the N-terminal arm, formed templates that supported wild-type levels of RNA replication but almost no transcription. These data show that mutations in the C-terminal loop of the N protein can disparately affect RNA replication and transcription, indicating that the N protein plays a role in modulating RNP template function beyond its structural role in RNA encapsidation.
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PMID:Mutations in the C-terminal loop of the nucleocapsid protein affect vesicular stomatitis virus RNA replication and transcription differentially. 1972 19

The phosphoprotein (P protein) of Chandipura virus (CHPV), a negative stranded RNA virus, is involved in both transcription and replication phases of the viral life cycle. The two Tryptophan (Trp) residues of CHPV, located at 105 and 135 respectively and two single Trp mutants W135F and W105F and a double Trp mutant W135F/W105F have been characterized by steady state and time-resolved fluorescence and phosphorescence at 298 K and 77 K. Results indicate that Trp135 is more buried with less polar and more hydrophobic environment whereas the Trp105 is solvent exposed. Quantum yields (capital EF, Cyrillic) suggest that the singlet-singlet (S <--> S) non-radiative energy transfer (ET) from the Trp135 to the Trp105 occurs with 66% efficiency. The simulation of the fluorescence spectra of the WT and the time resolved studies support the results. Lifetime and capital EF, Cyrillic of the single Trp mutants suggest an intrinsic static quenching of the Trp105. The results at 77 K indicate that the ET takes place from the lowest triplet state (T(1)) of the Trp105 to the T(1) of the Trp135 apart from the backward S <--> S ET from the Trp105 to the Trp135. The triplet-triplet (T <--> T) ET implies a distance of <10 A between the Trp105 and the Trp135. Using the crystal structure of Vesicular Stomatitis Virus (VSV) phosphoprotein exhibiting about 34% similarity with the CHPV P protein, a homology modelling of CHPV supports the observed distance between the Trp residues, the S <--> S ET efficiency and the environments of the Trp residues in CHPV.
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PMID:Characterization of the structure of the phosphoprotein of Chandipura virus, a negative stranded RNA virus probing intratryptophan energy transfer using single and double tryptophan mutants. 1989 67

Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the Lyssavirus genus and Rhabdoviridae family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in Escherichia coli, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of Lyssavirus genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related Vesiculovirus genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the Rhabdoviridae and the Paramyxoviridae.
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PMID:Structure of the nucleoprotein binding domain of Mokola virus phosphoprotein. 1990 36

The Borna disease virus (BDV) nucleoprotein (N) monomer resembles the nucleoprotein structures from rabies virus (RABV) and vesicular stomatitis virus (VSV). We show that BDV N assembles into ring- and string-like structures in the presence of 5' genomic BDV RNA. RNA induced polymerization is partly RNA-specific since polymerization is inefficient in the presence of 3' genomic BDV RNA or E. coli RNA. Mutagenesis of basic residues located in the cleft made up by the N- and C-terminal domains of N abrogate RNA-induced polymerization indicating that BDV N binds RNA similarly as observed in case of RABV and VSV N-RNA complexes. Bound RNA is not protected and sensitive to degradation. N-RNA polymers form complexes with the phosphoprotein P as required for functional transcription or replication units. Our data indicate that BDV N utilizes similar structural principles for N-RNA and N-P-RNA complex formation as observed for related negative strand RNA viruses.
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PMID:RNA induced polymerization of the Borna disease virus nucleoprotein. 1994 24


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