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

The first membrane-spanning domain (m1) of the model cis Golgi protein M (formerly called E1) from the avian coronavirus infectious bronchitis virus is required for targeting to the Golgi complex. When inserted in place of the membrane-spanning domain of a plasma membrane protein (vesicular stomatitis virus G protein), the chimeric protein ("Gm1") is retained in the Golgi complex of transfected cells. To determine the precise features of the m1 domain responsible for Golgi targeting, we produced single amino acid substitutions in m1 and analyzed their effects on localization of Gm1. Expression at the plasma membrane was used as the criterion for loss of Golgi retention. Rates of oligosaccharide processing were used as a measure of rate and efficiency of transport through the Golgi complex. We identified four uncharged polar residues that are critical for Golgi retention of Gm1 (Asn465, Thr469, Thr476, and Gln480). These residues line one face of a predicted alpha-helix. Interestingly, when the m1 domain of the homologous M protein from mouse hepatitis virus is inserted into the G protein reporter, the chimeric protein is not efficiently retained in the Golgi complex, but transported to the cell surface. Although it possesses three of the four residues we identified as important in the avian m1 sequence, other residues in the membrane-spanning domain from the mouse protein must prevent efficient recognition of the polar face within the lipid bilayer of the cis Golgi.
Mol Biol Cell 1993 Jul
PMID:Retention of a cis Golgi protein requires polar residues on one face of a predicted alpha-helix in the transmembrane domain. 840 Apr 55

p200 is a cytoplasmic protein that associates with vesicles budding from the trans-golgi network (TGN). The protein was identified by a monoclonal antibody AD7. We have used this antibody to analyze whether p200 functions in exocytic transport from the TGN to the apical or basolateral plasma membrane in Madin-Darby canine kidney cells. We found that transport of the viral marker proteins, influenza hemagglutinin (HA) to the apical surface or vesicular stomatitis virus glycoprotein (VSV G) to the basolateral surface in streptolysin O-permeabilized cells was not affected when p200 was depleted from both the membranes and the cytosol. When vesicles isolated from perforated cells were analyzed by equilibrium density gradient centrifugation, the p200 immunoreactive membranes did not comigrate with either the apical vesicle marker HA or the basolateral vesicle marker VSV G. Immunoelectron microscopy of perforated and double-labeled cells showed that the p200 positive vesicular profiles were not labeled by antibodies to HA or VSV G when the viral proteins were accumulated in the TGN. Furthermore, the p200-decorated vesicles were more electron dense than those labeled with the viral antibodies. Together, these results suggest that p200 does not function in the transport pathways that carry HA from the TGN to the apical surface or VSV G from the TGN to the basolateral surface.
Mol Biol Cell 1996 Jun
PMID:Analysis of the role of p200-containing vesicles in post-Golgi traffic. 881 1

The population dynamics of RNA viruses have an important influence on fitness variation and, in consequence, on the adaptative potential and virulence of this ubiquitous group of pathogens. Earlier work with vesicular stomatitis virus showed that large population transfers were reproducibly associated with fitness increases, whereas repeated transfers from plaque to plaque (genetic bottlenecks) lead to losses in fitness. We demonstrate here that repeated five-plaque to five-plaque passage series yield long-term fitness stability, except for occasional stochastic fitness jumps. Repeated five-plaque passages regularly alternating with two consecutive large population transmissions did not cause fitness losses, but did limit the size of fitness gains that would otherwise have occurred. These results underscore the profound effects of bottleneck transmissions in virus evolution.
Mol Gen Genet 1996 Oct 28
PMID:Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift. 891 17

RNA virus evolution is generally considered to be highly unpredictable, but tests of determinism in the evolution of competing populations during viral infections have not been performed. Here we study the fate of two closely related evolving quasispecies of vesicular stomatitis virus, by determining the relative concentration of a wild-type clone and a surrogate marked virus subclone (MARM-C) upon extensive competitive replication in a constant cell culture environment. A highly predictable nonlinear behaviour of the two competing populations was found. In addition, the presence of critical points, which are defined as points from which viral competitions may follow different trajectories, has been documented. Critical points were reached after nearly constant periods of time. The dynamics of relative fitness values for both competing populations were calculated during the replication passages. Concomitant with expected fitness gain of both competing viral populations (which follow the Red Queen hypothesis) a tendency for the MARM-C to gain less fitness than the wild-type was observed. Although fitness variations were noisy, this tendency was seen in all evolutionary replicas. Thus, despite the stochastic process of mutation that leads to a continuous generation of mutant genomes during RNA virus replication, a nonlinear, nearly deterministic evolutionary behaviour has been observed. It is proposed that such a behaviour is mediated by a low-pass filter (averaging of mutational noise signals) due to competitive selection among variants.
J Mol Biol 1996 Dec 06
PMID:Reproducible nonlinear population dynamics and critical points during replicative competitions of RNA virus quasispecies. 896 98

The role of COPII components in endoplasmic reticulum (ER)-Golgi transport, first identified in the yeast Saccharomyces cerevisiae, has yet to be fully characterized in higher eukaryotes. A human cDNA whose predicted amino acid sequence showed 70% similarity to the yeast Sec13p has previously been cloned. Antibodies raised against the human SEC13 protein (mSEC13) recognized a cellular protein of 35 kDa in both the soluble and membrane fractions. Like the yeast Sec13p, mSEC13 exist in the cytosol in both monomeric and higher-molecular-weight forms. Immunofluorescence microscopy localized mSEC13 to the characteristic spotty ER-Golgi intermediate compartment (ERGIC) in cells of all species examined, where it colocalized well with the KDEL receptor, an ERGIC marker, at 15 degrees C. Immunoelectron microscopy also localized mSEC13 to membrane structures close to the Golgi apparatus. mSEC13 is essential for ER-to-Golgi transport, since both the His6-tagged mSEC13 recombinant protein and the affinity-purified mSEC13 antibody inhibited the transport of restrictive temperature-arrested vesicular stomatitis virus G protein from the ER to the Golgi apparatus in a semi-intact cell assay. Moreover, cytosol immunodepleted of mSEC13 could no longer support ER-Golgi transport. Transport could be restored in a dose-dependent manner by a cytosol fraction enriched in the high-molecular-weight mSEC13 complex but not by a fraction enriched in either monomeric mSEC13 or recombinant mSEC13. As a putative component of the mammalian COPII complex, mSEC13 showed partially overlapping but mostly different properties in terms of localization, membrane recruitment, and dynamics compared to that of beta-COP, a component of the COPI complex.
Mol Cell Biol 1997 Jan
PMID:The mammalian homolog of yeast Sec13p is enriched in the intermediate compartment and is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus. 897 6

The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC-B and EMC-DV is mainly caused by release of some viral inhibitory factors from lymphocytes or phagocytic cells. Mice were infected with EMC-B and their splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases the viral inhibitory substance (VIS) which is neither immunoglobulin nor interferon. VIS has inhibitory effects against EMC-D in several kinds of cell lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post-treatment studies, VIS remarkably decreased the incidence of both illness and death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS activities existed in supernatant and pellet prepared from ultracentrifugation, but the properties of their activities could be differentiated quantitatively and qualitatively. It is speculated that VIS may be composed of at least two factors even though interferon may partially participate in one component of supernatant. The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might be due to the inhibition of the virus replication by VIS.
Mol Cells 1997 Apr 30
PMID:Characterization of viral inhibitory substance released from fused splenocyte. 916 27

In order to identify charged amino-acid residues of the cloned rat brain neurotensin (NT) receptor (NTR) that are critical for NT binding, we performed site-directed mutagenesis on the cDNA encoding this protein, followed by transient expression into mammalian COS-7 cells and in Xenopus laevis oocytes. Point substitutions of charged residues in the N-terminal part and in the 2nd and 3rd extracellular loop of the receptor either did not affect (125)I-Tyr3-NT binding or resulted in a decrease in binding affinity by a factor of 2-3. Mutations of amino acids Asp113 in the second transmembrane domain (TM) and of Arg149 or Asp150 in TM III yielded receptors that bound NT as efficiently as the native receptor. By contrast, replacement of the Asp139 residue in the 1st extracellular loop, or of Arg143 or Arg327-Arg328 residues at the top of TM III and in TM VI, respectively, completely abolished ligand binding. Confocal and EM immunocytochemical studies of the expression of these affected receptors, tagged with the C-terminal sequence of the vesicular stomatitis virus glycoprotein (VSV-G), indicated that this loss of binding was not due to altered receptor expression or to their improper insertion into the plasma membrane. When these mutated forms of neurotensin receptor were expressed into Xenopus oocytes, Asp139-Gly- and Arg143-Gly-modified receptors remained functional in spite of a lowered response to NT whereas the Arg327-Arg328 mutant form was totally insensitive to NT at concentrations up to 10 microM. In the case of the Arg327-Arg328 mutation, the observed insensibility to NT could be the result of a drastic conformational alteration of this mutant protein. By contrast, it would appear that Asp139 and Arg143 residues located in the first extracellular loop of the receptor may be directly involved in the interaction of the receptor with neurotensin.
Brain Res Mol Brain Res 1997 Jun
PMID:Identification in the rat neurotensin receptor of amino-acid residues critical for the binding of neurotensin. 919 Nov 7

The molecular interactions between the CD8 co-receptor dependent N15 and N26 T cell receptors (TCRs) and their common ligand, the vesicular stomatitis virus octapeptide (VSV8) bound to H-2Kb, were studied to define the docking orientation(s) of MHC class I restricted TCRs during immune recognition. Guided by the molecular surfaces of the crystallographically defined peptide/MHC and modeled TCRs, a series of mutations in exposed residues likely contacting the TCR ligand were analyzed for their ability to alter peptide-triggered IL-2 production in T cell transfectants. Critical residues which diminished antigen recognition by 1000 to 10,000-fold in molar terms were identified in both N15 Valpha (alphaE94A or alphaE94R, Y98A and K99) and Vbeta (betaR96A, betaW97A and betaD99A) CDR3 loops. Mutational analysis indicated that the Rp1 residue of VSV8 is critical for antigen recognition of N15 TCR, but R62 of H-2Kb is less critical. More importantly, the alphaE94R mutant could be fully complemented by a reciprocal charge reversal at Kb R62 (R62E). This result suggests a direct interaction between N15 TCR Valpha E94R and Kb R62E residues. As Rp1 of VSV8 is adjacent to R62 in the VSV8/Kb complex and essential for T cell activation, this orientation implies that the N15 Valpha CDR3 loop interacts with the N-terminal residues of VSV8 with the Valpha domain docking to the Kb alpha2 helix while the N15 Vbeta CDR3 loop interacts with the more C-terminal peptide residues and the Vbeta domain overlies the Kb alpha1 helix. An equivalent orientation is suggested for N26, a second VSV8/Kb specific TCR. Given that genetic analysis of two different class II MHC-restricted TCRs and two crystallographic studies of class I restricted TCRs offers a similar overall orientation of V domains relative to alpha-helices, these data raise the possibility of a common docking mode between TCRs and their ligands regardless of MHC restriction.
J Mol Biol 1997 Aug 15
PMID:Topology of T cell receptor-peptide/class I MHC interaction defined by charge reversal complementation and functional analysis. 926 59

Rubella virus contains three structural proteins, capsid, E2, and E1. E2 and E1 are type I membrane glycoproteins that form a heterodimer in the endoplasmic reticulum (ER) before they are transported to and retained in the Golgi complex, where virus assembly occurs. The bulk of unassembled E2 and E1 subunits are not transported to the Golgi complex. We have recently shown that E2 contains a Golgi-targeting signal that mediates retention of the E2-E1 complex (T. C. Hobman, L. Woodward, and M. G. Farquhar, Mol. Biol. Cell 6:7-20, 1995). The focus of this study was to determine if E1 glycoprotein also contains intracellular targeting information. We constructed a series of chimeric reporter proteins by fusing domains from E1 to the ectodomains of two other type I membrane proteins which are normally transported to the cell surface, vesicular stomatitis virus G protein (G) and CD8. Fusion of the E1 transmembrane and cytoplasmic regions, but not analogous domains from two control membrane proteins, to the ectodomains of G and CD8 proteins caused the resulting chimeras to be retained in the ER. Association of the ER-retained chimeras with known ER chaperone proteins was not detected. ER localization required both the transmembrane and cytoplasmic regions of E1, since neither of these domains alone was sufficient to retain the reporter proteins. Increasing the length of the E1 cytoplasmic domain by 10 amino acids completely abrogated ER retention. This finding also indicated that the chimeras were not retained as a result of misfolding. In summary, we have identified a new type of ER retention signal that may function to prevent unassembled E1 subunits and/or immature E2-E1 dimers from reaching the Golgi complex, where they could interfere with viral assembly. Accordingly, assembly of E2 and E1 would mask the signal, thereby allowing transport of the heterodimer from the ER.
 ...
PMID:Characterization of an endoplasmic reticulum retention signal in the rubella virus E1 glycoprotein. 931 50

The matrix protein of vesicular stomatitis virus (VSV) plays a pivotal role in viral assembly. We previously demonstrated the ability of M protein to self-associate at low salt concentrations. Now, we show the ability of M protein to polymerize in the presence of ZnCl2 in a nucleation-dependent manner. Analysis of kinetics revealed that the nuclei are probably made of three or four molecules of M. These results are consistent with the idea that in vitro self association of M protein is not due to amorphous aggregation but rather reflects an intrinsic ability of M to polymerize. Using attenuated total reflectance Fourier transform infrared spectroscopy, we showed that M polymerization is associated with an increase in the beta-sheet content of the protein. We propose a model explaining both the apparent M protein solubility in infected cells and how M polymerization could promote viral assembly. Data available for other negative strand viruses suggest that M polymerization may be the general basis of viral assembly.
J Mol Biol 1997 Dec 19
PMID:Conformational flexibility and polymerization of vesicular stomatitis virus matrix protein. 940 60


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