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 spike glycoprotein (G protein) of rabies virus (CVS strain) expressed in HeLa cells from cloned cDNA mediated membrane fusion after exposure to pHs of 6.1 or below. Chemical crosslinking showed that the rabies G protein, like the vesicular stomatitis virus (VSV) G protein, could be crosslinked to dimers and trimers, indicating that rabies G protein is a trimer. However, unlike the VSV G protein, rabies G protein trimers were not stable to sedimentation in sucrose gradients, even at a mildly acidic pH which stabilizes the VSV G protein trimers. In addition, we report that the expressed rabies virus G protein was functional because it could assemble into VSV particles (tsO45) lacking VSV G protein and rescue infectivity. These VSV (rabies) pseudotypes were neutralized only by an antibody to the rabies G protein. We also examined the properties of a hybrid protein containing the extracellular domain of the rabies virus glycoprotein and the transmembrane and cytoplasmic domains of the VSV G protein. This protein was transported to the cell surface and could be crosslinked to form dimers and trimers, but had little or no detectable membrane fusion activity. The lack of fusion activity was paradoxical because the hybrid protein could rescue VSV infectivity, although the titers were lower than those obtained with the wild-type rabies G protein.
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PMID:Membrane fusion activity, oligomerization, and assembly of the rabies virus glycoprotein. 166 Feb

Both fixed and street rabies virus when cultivated in McCoy cells caused cytopathic changes 24 to 72 h after infection, depending on the multiplicity of infection. The cytopathic effect (CPE) was easily recognizable and resembles that induced by other members of the Rhabdovirus group, such as vesicular stomatitis virus, in several cell cultures. Higher titers of the Pasteur strain (PV) of fixed rabies virus were found in supernatants of McCoy cells when compared to those in VERO cells. The virus titer increased with the number of passages attaining a high titer after three passages. Rabies antigens were detected by direct immunofluorescence labeling in most McCoy cells of the infected culture, and specific antibodies neutralized the virus growth and CPE. There was also inhibition by treatment of the cells with human interferon (HuIFN) -alpha or -gamma, but not by murine interferon (MuIFN) -alpha, -beta or -gamma. Rabies-infected McCoy cell cultures may provide a useful assay system, based on the induction of CPE, the high virus production and the sensitivity to IFN.
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PMID:Cytopathic effect induced by rabies virus in McCoy cells. 169 Dec 1

Our recent efforts have been directed at the development of selective inhibitors of different classes of viruses, including adeno, pox, and herpesviruses [herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], (+/-)RNA viruses (reo- and rotavirus), (-)RNA viruses (influenza, parainfluenza, measles, respiratory syncytial, vesicular stomatitis and rabies virus) and retroviruses [i.e. human immunodeficiency virus (HIV), the causative agent of AIDS]. In this search, the following molecular targets were envisaged: for DNA viruses in general, the viral DNA polymerase; for herpes simplex virus and varicella-zoster virus, the viral DNA polymerase via a specific phosphorylation by the viral 2'-deoxythymidine (dThd) kinase; for (+/-)RNA and (-)RNA viruses, S-adenosylhomocysteine (SAH) hydrolase, a key enzyme in transmethylation reactions required for the maturation of viral mRNA; for retroviruses, reverse transcriptase as initiator of virus replication and/or cell transformation; and for several enveloped viruses (i.e. retro-, herpes- and rhabdoviruses), virus adsorption to the outer cell membrane. Several new compounds have been developed that appear to act at these targets: i.e. (E)-5-(2-bromovinyl)-2'-deoxyuridine [bromovinyldeoxyuridine (BVDU)] and derivatives thereof [i.e. carbocyclic BVDU (C-BVDU)] as well as derivatives of acyclovir (i.e. 8-substituted acyclovir derivatives) as inhibitors of herpesviruses; (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of DNA viruses and retroviruses; acyclic and carbocyclic analogues of adenosine [such as (S)-9-(2,3-dihydroxypropyl)adenine [S)-DHPA), carbocyclic 3-deazaadenosine (C-c3Ado), (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (AHPA) alkyl esters, neplanocin A, 3-deazaneplanocin A and the 5'-nor derivatives of neplanocin A and 3-deazaneplanocin A] as inhibitors of (+/-)RNA and (-)RNA viruses; 2',3'-dideoxynucleoside analogues as inhibitors of retroviruses; and sulfated polysaccharides (i.e. heparin, dextran sulfate, pentosan polysulfate, mannan sulfate), sulfated polyvinylalcohol and co-polymers of sulfated polyvinylalcohol with acrylic acid as inhibitors of retro-, herpes- and rhabdoviruses.
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PMID:Selective virus inhibitors. 169 49

The nucleotide sequences of the 3' extracistronic (leader) and 5' extracistronic (trailer) regions were determined for genomic RNA (vRNA) of human respiratory syncytial virus (RSV) strain A2. To sequence the 3' leader region, vRNA was extracted from purified virions, size-selected, polyadenylated, copied into cDNA, amplified by the polymerase chain reaction, cloned, and sequenced. The 3' leader sequence is 44 nt, which is somewhat shorter than its counterparts (50 to 70 nt) in other nonsegmented negative-strand viruses sequenced to date. The 5' trailer region was mapped and sequenced in part directly by dideoxynucleotide sequencing of vRNA. The sequence was confirmed and completed by analysis of cDNA clones derived from vRNA. The 5' trailer sequence is 155 nt in length, which is substantially longer than its counterparts (40 to 70 nt) in other nonsegmented negative-strand viruses. Ten of the 11 terminal nt of the 3' leader and 5' trailer regions were complementary. Among the other paramyxoviruses, the terminal 5 to 16 nt of the leader and trailer regions are highly conserved, but the corresponding RSV sequences were identical to the others only for the terminal 2 nt of each end. Surprisingly, the termini of the RSV leader and trailer regions were in somewhat better agreement with those of the rhabdoviruses vesicular stomatitis virus and rabies virus, sharing identity for the first 3 or 4 nt.
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PMID:Nucleotide sequences of the 3' leader and 5' trailer regions of human respiratory syncytial virus genomic RNA. 184 Jul 12

Guanine 7-N-oxide (G-7-Ox) was examined for its antiviral activity against 9 viruses based on plaque reduction, neuraminidase activity reduction, a fluorescent antibody technique or ELISA. The following viruses were included in the tests: influenza, Sendai, simian virus 5 (SV5), respiratory syncytial, western equine encephalitis, Japanese encephalitis, vesicular stomatitis, rabies and polio. G-7-Ox showed broad anti-RNA viral activity against all viruses tested, except for poliovirus. Inhibition of persistent SV5 infection by G-7-Ox indicates that its antiviral activity is independent of cytotoxicity.
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PMID:Inhibitory effect of a new antibiotic, guanine 7-N-oxide, on the replication of several RNA viruses. 196 74

The complete nucleotide sequence of the large (L) polymerase gene of human respiratory syncytial virus (RSV) strain A2 was determined by analysis of cloned-cDNAs representing the entire gene and confirmed in part by dideoxy sequencing of genomic RNA. The RSV L gene is 6578 nucleotides in length and contains a single major open reading frame that encodes a protein of 2165 amino acids. The molecular weight (250,226) and amino acid composition of the deduced RSV L protein are similar to those of other negative-strand RNA viruses. Regions of statistically significant amino acid sequence similarity were identified in pairwise global alignments of the RSV L protein with its counterparts in four paramyxoviruses (parainfluenza virus type 3, Sendai virus, measles virus, Newcastle disease virus) and two rhabdoviruses (rabies virus, vesicular stomatitis virus). In addition, amino acid sequence alignments showed that the RSV L protein has a 70-amino acid amino-terminal extension relative to the others. This is suggested to be due to the acquisition of gene overlap of the RSV L gene with its upstream neighbor, the 22K (M2) gene and the use of a new translational start site. The most highly related region among these seven proteins is located within the amino-terminal half, representing approximately 20% of each protein sequences. This region contains six discrete segments that are colinear and highly conserved in each paramyxovirus and rhabdovirus L protein, and three of these overlapped with sequence motifs found previously in other RNA-dependent RNA and DNA polymerases. A phylogenetic tree was constructed from the paramyxovirus and rhabdovirus L protein sequences to further define their relationships. The branching order indicates that RSV represents a lineage within the paramyxovirus family which is relatively distinct from the others, which in turn are more closely interrelated. Among these other members of the family Paramyxoviridae, the branching order does not entirely conform to their current taxonomic organization, providing support for its reevaluation.
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PMID:Sequence analysis of the polymerase L gene of human respiratory syncytial virus and predicted phylogeny of nonsegmented negative-strand viruses. 205 82

We have determined the nucleotide sequence of the L gene of vesicular stomatitis virus (VSV), New Jersey serotype (Ogden strain) by primer extension dideoxy sequencing of the genomic RNA with reverse transcriptase. This analysis completes the entire genomic sequence of the VSVNJ (Ogden). Comparison of the deduced amino acid sequence of this L protein with those reported for L proteins of Indiana serotype and Hazelhurst strain of New Jersey serotype revealed an extensive sequence similarity among all three proteins. The comparison was further extended to the L proteins of other nonsegmented negative-strand RNA viruses, namely the rabies virus and four members of the paramyxovirus family: measles, Newcastle disease, human parainfluenza 3, and Sendai viruses. Our findings confirmed the existence of conserved as well as unique domains in the L proteins, suggesting an evolutionary relationship among these viruses.
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PMID:Nucleotide sequence analysis of the L gene of vesicular stomatitis virus (New Jersey serotype): identification of conserved domains in L proteins of nonsegmented negative-strand RNA viruses. 215 16

The large (L) protein subunit of unsegmented negative-strand RNA virus polymerases is thought to be responsible for the majority of enzymic activities involved in viral transcription and replication. In order to gain insight into this multifunctional role we compared the deduced amino acid sequences of five L proteins of rhabdoviruses (vesicular stomatitis virus and rabies virus) or paramyxoviruses (Sendai virus, Newcastle disease virus and measles virus). Statistical analysis showed that they share an atypical amino acid usage, outlining the uniqueness of the negative-strand virus life style. Similarity studies between L proteins traced evolutionary relationships in partial disagreement with the present taxonomic arrangement of this group of viruses. The five L proteins exhibit a high degree of homology along most of their length, with strongly invariant amino acids embedded in conserved blocks separated by variable regions, suggesting a structure of concatenated functional domains. The most highly conserved central block contains the probable active site for RNA synthesis. We tentatively identified some other functional sites, distributed around this central core, that would naturally work together to assure the polymerase activity. This provides detailed guidelines for the future study of L proteins by site-directed mutagenesis.
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PMID:Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: theoretical assignment of functional domains. 216 Oct 49

A panel of neutralizing and nonneutralizing monoclonal antibodies (MAbs) to the Indiana strain of vesicular stomatitis virus (VSV-IND) were used to select nonbinding VSV-IND mutants. In addition, virus was passaged against high titered polyclonal antisera to select for poorly neutralized virus mutants. Nucleic acid sequencing localized mutations in the surface spike glycoprotein (G protein) sequence which were associated with decreased neutralization by polyclonal antisera and with nonbinding by neutralizing and nonneutralizing MAbs. The major neutralization epitope, the A epitope, is composed of at least two regions that are widely separated in the primary G protein sequence. We found evidence for both continuous and discontinuous determinants within the A epitope and found one strongly selected region that may function as an antigenic loop. The high degree of sequence homology between VSV-IND and the other major VSV serotype, VSV-New Jersey (VSV-NJ) allowed us to predict some of the neutralization epitopes of VSV-New Jersey. Alignment of VSV and rabies virus sequences revealed that major neutralizing epitopes in VSV correspond to sites of carbohydrate attachment in rabies. This may be of significance in the evolution of rhabdoviruses.
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PMID:Sequences of the major antibody binding epitopes of the Indiana serotype of vesicular stomatitis virus. 241 17

We have carried out an exhaustive search for amino acid sequence similarities between vesicular stomatitis virus (VSV) proteins and database entries. Unexpectedly, we found that the L polymerase protein contains two blocks of sequence (residues 725-1102 and 1291-1671) with distant but statistically significant similarity to the catalytic domain of tyrosine-specific protein kinases. The first kinase-like region is most similar to members of the Abl subfamily, Fes and Fps (26.6% and 27.3% identity, respectively), whereas the second region is closest to members of the platelet-derived growth factor receptor (PDGFR) subfamily, PDGFR and Kit (30.4% and 25.9% identity, respectively). Multiple alignment of the catalytic domain of these kinases to all three rhabdovirus L protein sequences available (VSV Indiana, VSV New Jersey, and rabies) revealed that the polymerases contain many but not all residues well conserved in the protein kinase family. Similarity was highest for VSV Indiana and lowest for rabies. We conclude that the kinase-like regions in the rhabdoviral L proteins are probably very distantly related to the protein kinase family. The similarities could either reflect contemporary protein kinase activity or represent some other function(s) associated with these large multifunctional polymerase proteins. Our findings also shed new light on questions of the origins and evolution of RNA viruses.
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PMID:Two domains distantly related to protein-tyrosine kinases in the vesicular stomatitis virus polymerase. 254 20


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