scholarly journals The Carboxyl Segment of the Mumps Virus V Protein Associates with Stat Proteins in Vitro Via a Tryptophan-Rich Motif

Virology ◽  
2002 ◽  
Vol 300 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Machiko Nishio ◽  
Dominique Garcin ◽  
Viviane Simonet ◽  
Daniel Kolakofsky
Keyword(s):  
Mumps Virus ◽  
V Protein ◽  
Stat Proteins

scholarly journals A Point Mutation, E95D, in the Mumps Virus V Protein Disengages STAT3 Targeting from STAT1 Targeting

2009 ◽  
Vol 83 (13) ◽  
pp. 6347-6356 ◽  
Author(s):  
Mamta Puri ◽  
Ken Lemon ◽  
W. Paul Duprex ◽  
Bertus K. Rima ◽  
Curt M. Horvath
Keyword(s):  
Cultured Cells ◽  
Mumps Virus ◽  
Single Amino Acid ◽  
V Protein ◽  
Large Plaque ◽  
Stat Proteins ◽  
Cellular Genes ◽  
Ubiquitin Ligase Complex ◽  
Cellular Signal ◽  
Cellular Components

ABSTRACT Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V protein that can assemble a ubiquitin ligase complex from cellular components, leading to the destruction of cellular signal transducer and activator of transcription (STAT) proteins. While many V proteins target the interferon-activated STAT1 or STAT2 protein, mumps virus V protein is unique in its ability to also target STAT3 for ubiquitin modification and proteasome-mediated degradation. Here we report that a single amino acid substitution in the mumps virus V protein, E95D, results in defective STAT3 targeting while maintaining the ability to target STAT1. Results indicate that the E95D mutation disrupts the ability of the V protein to associate with STAT3. A recombinant mumps virus carrying the E95D mutation in its P and V proteins replicates normally in cultured cells but fails to induce targeting of STAT3. Infection with the recombinant virus results in the differential regulation of a number of cellular genes compared to wild-type mumps virus and increases cell death in infected cells, producing a large-plaque phenotype.

scholarly journals Single amino acid changes in the mumps virus haemagglutinin–neuraminidase and polymerase proteins are associated with neuroattenuation

2009 ◽  
Vol 90 (7) ◽  
pp. 1741-1747 ◽  
Author(s):  
Tahir H. Malik ◽  
Candie Wolbert ◽  
Laura Nerret ◽  
Christian Sauder ◽  
Steven Rubin
Keyword(s):  
Amino Acid ◽  
Clinical Isolate ◽  
Amino Acid Change ◽  
Mumps Virus ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Supporting Evidence ◽  
L Protein ◽  
Single Amino Acid Change

It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91→Thr), haemagglutinin–neuraminidase (HN; Ser-466→Asn) and polymerase (L; Ile-736→Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the F protein, despite having a dramatic effect on protein function in vitro, was previously shown to not be involved in the observed neuroattenuation, highlighting the importance of conducting confirmatory in vivo studies. This report provides additional supporting evidence for the role of the HN protein as a virulence factor and, as far as is known, is the first report to associate an amino acid change in the L protein with mumps virus neuroattenuation.

Detection and characterization of mumps virus V protein

Virology ◽  
1990 ◽  
Vol 178 (1) ◽  
pp. 247-253 ◽  
Author(s):  
Kaoru Takeuchi ◽  
Kiyoshi Tanabayashi ◽  
Michiko Hishiyama ◽  
Yasuko K. Yamada ◽  
Akio Yamada ◽  
...  
Keyword(s):  
Mumps Virus ◽  
V Protein

scholarly journals C-Terminal Region of STAT-1α Is Not Necessary for Its Ubiquitination and Degradation Caused by Mumps Virus V Protein

2002 ◽  
Vol 76 (24) ◽  
pp. 12683-12690 ◽  
Author(s):  
Noriko Yokosawa ◽  
Shin-ichi Yokota ◽  
Toru Kubota ◽  
Nobuhiro Fujii
Keyword(s):  
Amino Acid ◽  
Transcriptional Activation ◽  
Tandem Repeats ◽  
Mumps Virus ◽  
Terminal Region ◽  
Single Amino Acid ◽  
Luciferase Reporter ◽  
Enhancer Element ◽  
V Protein ◽  
Gene Assay

ABSTRACT Constitutive levels of production of STAT-1 were reduced by 10 h postinfection (p.i.) and significantly lost by 24 h p.i. in FL cells acutely infected with mumps virus (MuV). This result was consistent with that observed in previous studies and experiments with cells persistently infected with MuV (FLMT cells). There was a marked decrease in the amount of STAT-1 in cells expressing MuV accessory protein V (MuV-V). Furthermore, single amino acid substitutions in the Cys-rich region of V protein (Vc189a, Vc207a, and Vc214a) showed that each cysteine residue plays an important role in the decrease in STAT-1 production, but substitution of a histidine residue at amino acid position 203 had no effect. These events and the resultant suppression of the alpha interferon (IFN-α) response were confirmed by a luciferase reporter gene assay with five tandem repeats of the IFN-α-stimulated response element as an enhancer element of the firely luciferase gene. STAT-1 production was restored and detectable in FLMT cells treated with a proteosome inhibitor, such as MG132 or lactacystin. In the presence of MG132, ubiquitination of STAT-1 and the interaction of MuV-V with STAT-1 were demonstrated in FLMT cells by immunoprecipitation with anti-STAT-1 antibody. The same results for the interaction and ubiquitination were obtained in experiments with an expression vector for a C-terminal deletion mutant of STAT-1. The truncated STAT-1 molecules were degraded in the presence of MuV-V. Therefore, the C-terminal region (transcriptional activation and Src homology 2 domains) of STAT-1 is not necessary for its degradation caused by MuV-V. Our data suggest that MuV-V promotes ubiquitination and degradation of STAT-1.

scholarly journals The V Protein of Mumps Virus Plays a Critical Role in Pathogenesis

2011 ◽  
Vol 86 (3) ◽  
pp. 1768-1776 ◽  
Author(s):  
P. Xu ◽  
P. Luthra ◽  
Z. Li ◽  
S. Fuentes ◽  
J. A. D'Andrea ◽  
...  
Keyword(s):  
Critical Role ◽  
Mumps Virus ◽  
V Protein

Endocrine and physiological events from ovulation to establishment of pregnancy in cattle

2001 ◽  
Vol 26 (1) ◽  
pp. 81-91 ◽  
Author(s):  
W.W. Thatcher ◽  
M. Binelli ◽  
D. Arnold ◽  
R. Mattos ◽  
L. Badinga ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Post Partum ◽  
Secretory Response ◽  
Embryo Survival ◽  
Endometrial Cells ◽  
Stat Proteins ◽  
In Vivo Experiments ◽  
Feeding Diets

AbstractA series of in vitro and in vivo experiments were conducted to characterise the dialogue between embryo and maternal units relative to the mechanisms controlling embryo survival in dairy cattle. Endometrial explants from pregnant cows had an attenuated PGF2α secretory response following treatment with melittin (stimulator of PLA2) and phorbol 12, 13 dibutyrate (PDBu). Thus previous exposure to the conceptus appears to regulate the endometrial synthetic pathway at a point coincident with or distal to PLA2 as well as inhibit PKC or PKC mediated events. Endometrial explants collected from cows receiving intrauterine infusions of rblFN-τ had a reduced secretory response following stimulation with PDBu indicating attenuation in PKC activity. Based upon tyrosine-phosphorylation of STAT-proteins and their translocation to the nucleus after treatment with rbIFN-τ, the JAK-STAT pathway is functional in immortalised bovine endometrial cells (BEND cells). Bend cells, exposed to rblFN-τ, reduced PDBu induction of PGF2α secretion and also decreased protein expression of Cox-2 and PLA. RblFN-τ clearly reduced PKC mediated events leading to an antiluteolytic response in endometrial cells. Feeding diets containing 2.6, 5.2 and 7.8% Menhaden fish meal to lactating dairy cows reduced uterine secretion of PGF2α following sequential injections of oestradiol and oxytocin. Thus antiluteolytic effects in early pregnancy may be amplified by feeding by-pass fats. Pregnancy rate to a timed insemination at first service post-partum is increased in association with injection of bST(500 mg; sc) given at insemination. Furthermore injection of bST at time of insemination in superovulated donor cows increased the number of blastocysts and reduced number of unfertilised embryos. Prospects of integrating novel strategies to improve embryo development and survival into reproductive management systems appear to be attainable in high producing dairy cows.

scholarly journals Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors

2020 ◽  
Vol 19 (10) ◽  
pp. 1619-1631
Author(s):  
Elez D. Vainer ◽  
Juliane Kania-Almog ◽  
Ghadeer Zatara ◽  
Yishai Levin ◽  
Gilad W. Vainer
Keyword(s):  
Tumor Cells ◽  
Expression Patterns ◽  
Interferon Γ ◽  
Short Exposure ◽  
Clinical Samples ◽  
Temporal Regulation ◽  
Stat Proteins ◽  
Clinical Biomarkers

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon-γ induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon-γ protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.

scholarly journals Mumps Virus Decreases Testosterone Production and Gamma Interferon-Induced Protein 10 Secretion by Human Leydig Cells

2003 ◽  
Vol 77 (5) ◽  
pp. 3297-3300 ◽  
Author(s):  
Ronan Le Goffic ◽  
Thomas Mouchel ◽  
Annick Ruffault ◽  
Jean-Jacques Patard ◽  
Bernard Jégou ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Mumps Virus ◽  
Gamma Interferon ◽  
Testosterone Secretion ◽  
Testosterone Production

ABSTRACT Mumps virus is responsible for sterility. Here, we show that the mumps virus infects Leydig cells in vitro and totally inhibits testosterone secretion and that ribavirin in mumps virus-infected Leydig cell cultures completely restores testosterone production. Moreover, we show that gamma interferon-induced protein 10 (IP-10) is highly expressed by mumps virus-infected Leydig cells and that ribavirin does not block IP-10 production.

The mumps virus V protein is unstable in virus infected cells

1993 ◽  
Vol 133 (1-2) ◽  
pp. 201-209 ◽  
Author(s):  
A. Hu ◽  
S. Schwartz ◽  
G. Utter ◽  
C. �rvell ◽  
J. K�vamees ◽  
...  
Keyword(s):  
Mumps Virus ◽  
V Protein ◽  
Infected Cells

scholarly journals Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization

2012 ◽  
Vol 86 (18) ◽  
pp. 9929-9940 ◽  
Author(s):  
John B. Johnson ◽  
Douglas S. Lyles ◽  
Martha A. Alexander-Miller ◽  
Griffith D. Parks
Keyword(s):  
Host Cell ◽  
Vesicular Stomatitis Virus ◽  
Viral Vectors ◽  
Mumps Virus ◽  
Biologically Active ◽  
Host Cell Membrane ◽  
Relative Contribution ◽  
Virion Envelope ◽  
Vesicular Stomatitis

Enveloped viruses can incorporate host cell membrane proteins during the budding process. Here we demonstrate that mumps virus (MuV) and vesicular stomatitis virus (VSV) assemble to include CD46 and CD55, two host cell regulators which inhibit propagation of complement pathways through distinct mechanisms. Using viruses which incorporated CD46 alone, CD55 alone, or both CD46 and CD55, we have tested the relative contribution of these regulators in resistance to complement-mediated neutralization. Virion-associated CD46 and CD55 were biologically active, with VSV showing higher levels of activity of both cofactors, which promoted factor I-mediated cleavage of C3b into iC3b as well as decay-accelerating factor (DAF) activity against the C3 convertase, than MuV. Time courses ofin vitroneutralization with normal human serum (NHS) showed that both regulators could delay neutralization, but viruses containing CD46 alone were neutralized faster and more completely than viruses containing CD55 alone. A dominant inhibitory role for CD55 was most evident for VSV, where virus containing CD55 alone was not substantially different in neutralization kinetics from virus harboring both regulators. Electron microscopy showed that VSV neutralization proceeded through virion aggregation followed by lysis, with virion-associated CD55 providing a delay in both aggregation and lysis more substantial than that conferred by CD46. Our results demonstrate the functional significance of incorporation of host cell factors during virion envelope assembly. They also define pathways of virus complement-mediated neutralization and suggest the design of more effective viral vectors.

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