scholarly journals M135R Is a Novel Cell Surface Virulence Factor of Myxoma Virus

2006 ◽  
Vol 81 (1) ◽  
pp. 106-114 ◽  
Author(s):  
John W. Barrett ◽  
Joanna Sypula ◽  
Fuan Wang ◽  
Lindsay R. Alston ◽  
Zhuhong Shao ◽  
...  
Keyword(s):  
Cell Surface ◽  
Virulence Factor ◽  
Type I Interferon ◽  
Sequence Similarity ◽  
Myxoma Virus ◽  
Early Gene ◽  
European Rabbit ◽  
Type I ◽  
Amino Terminal ◽  
A Cell

ABSTRACT Myxoma virus (MV) encodes a cell surface protein (M135R) that is predicted to mimic the host alpha/beta interferon receptor (IFN-α/β-R) and thus prevent IFN-α/β from triggering a host antiviral response. This prediction is based on sequence similarity to B18R, the viral IFN-α/β-R from vaccinia virus (VV), which has been demonstrated to bind and inhibit type I interferons. However, M135R is only half the size of VV B18R. All other poxvirus-encoded IFN-α/β-R homologs align only to the amino-terminal half of M135R. Peptide antibodies raised against M135R were used for immunoblotting and immunofluorescence and indicate that M135R is expressed as an early gene and that the product is a cell surface N-linked glycoprotein that is not secreted. In contrast to the predicted properties of M135R as an inhibitor of type I interferon, all binding and inhibition assays designed to demonstrate whether M135R can interact with IFN-α/β have been negative. However, pathogenesis studies with a targeted M135-knockout MV construct (vMyx135KO) indicate that the deletion of M135R severely attenuates MV pathogenesis in the European rabbit. We propose that M135R is an important immunomodulatory virulence factor for myxomatosis but that the target immune ligand is not from the predicted type I interferon family and remains to be identified.

scholarly journals Myxoma virus M128L is expressed as a cell surface CD47-like virulence factor that contributes to the downregulation of macrophage activation in vivo

Virology ◽  
2005 ◽  
Vol 337 (1) ◽  
pp. 55-67 ◽  
Author(s):  
C.M. Cameron ◽  
J.W. Barrett ◽  
M. Mann ◽  
A. Lucas ◽  
Grant McFadden
Keyword(s):  
Cell Surface ◽  
Virulence Factor ◽  
Macrophage Activation ◽  
Myxoma Virus ◽  
A Cell

scholarly journals Molecular regulation of GLUT-4 targeting in 3T3-L1 adipocytes.

1995 ◽  
Vol 130 (5) ◽  
pp. 1081-1091 ◽  
Author(s):  
B J Marsh ◽  
R A Alm ◽  
S R McIntosh ◽  
D E James
Keyword(s):  
Cell Surface ◽  
Glucose Transporter ◽  
Subcellular Fractionation ◽  
Molecular Regulation ◽  
Surface Distribution ◽  
Amino Terminal ◽  
Glut 4 ◽  
Dileucine Motif ◽  
A Cell ◽  
Insulin Dependent

Insulin stimulates glucose transport in muscle and adipose tissue by triggering the movement of the glucose transporter GLUT-4 from an intracellular compartment to the cell surface. Fundamental to this process is the intracellular sequestration of GLUT-4 in nonstimulated cells. Two distinct targeting motifs in the amino and carboxy termini of GLUT-4 have been previously identified by expressing chimeras comprised of portions of GLUT-4 and GLUT-1, a transporter isoform that is constitutively targeted to the cell surface, in heterologous cells. These motifs-FQQI in the NH2 terminus and LL in the COOH terminus-resemble endocytic signals that have been described in other proteins. In the present study we have investigated the roles of these motifs in GLUT-4 targeting in insulin-sensitive cells. Epitope-tagged GLUT-4 constructs engineered to differentiate between endogenous and transfected GLUT-4 were stably expressed in 3T3-L1 adipocytes. Targeting was assessed in cells incubated in the presence or absence of insulin by subcellular fractionation. The targeting of epitope-tagged GLUT-4 was indistinguishable from endogenous GLUT-4. Mutation of the FQQI motif (F5 to A5) caused GLUT-4 to constitutively accumulate at the cell surface regardless of expression level. Mutation of the dileucine motif (L489L490 to A489A490) caused an increase in cell surface distribution only at higher levels of expression, but the overall cells surface distribution of this mutant was less than that of the amino-terminal mutants. Both NH2- and COOH-terminal mutants retained insulin-dependent movement from an intracellular to a cell surface locale, suggesting that neither of these motifs is involved in the insulin-dependent redistribution of GLUT-4. We conclude that the phenylalanine-based NH2-terminal and the dileucine-based COOH-terminal motifs play important and distinct roles in GLUT-4 targeting in 3T3-L1 adipocytes.

A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis

2019 ◽  
Vol 101 ◽  
pp. 1-16 ◽  
Author(s):  
Martina Severa ◽  
Fabiana Rizzo ◽  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Elena Giacomini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Type I Interferon ◽  
Type I ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

scholarly journals AG alpha 1 is the structural gene for the Saccharomyces cerevisiae alpha-agglutinin, a cell surface glycoprotein involved in cell-cell interactions during mating.

1989 ◽  
Vol 9 (8) ◽  
pp. 3155-3165 ◽  
Author(s):  
P N Lipke ◽  
D Wojciechowicz ◽  
J Kurjan
Keyword(s):  
Cell Surface ◽  
Fusion Protein ◽  
Structural Gene ◽  
Signal Sequence ◽  
Positive Control ◽  
Complementation Group ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Amino Terminal ◽  
A Cell

We have cloned the alpha-agglutinin structural gene, AG alpha 1, by the isolation of alpha-specific agglutination-defective mutants, followed by isolation of a complementing plasmid. Independently isolated alpha-specific agglutination-defective mutations were in a single complementation group, consistent with biochemical results indicating that the alpha-agglutinin is composed of a single polypeptide. Mapping results suggested that the complementation group identified by these mutants is allelic to the ag alpha 1 mutation identified previously. Expression of AG alpha 1 RNA was alpha specific and inducible by a-factor. Sequences similar to the consensus sequences for positive control by MAT alpha 1 and pheromone induction were found upstream of the AG alpha 1 initiation codon. The AG alpha 1 gene could encode a 650-amino-acid protein with a putative signal sequence, 12 possible N-glycosylation sites, and a high proportion of serine and threonine residues, all of which are features expected for the alpha-agglutinin sequence. Disruption of the AG alpha 1 gene resulted in failure to express alpha-agglutinin and loss of cellular agglutinability in alpha cells. An Escherichia coli fusion protein containing 229 amino acids of the AG alpha 1 sequence was recognized by an anti-alpha-agglutinin antibody. In addition, the ability of this antibody to inhibit agglutination was prevented by this fusion protein. These results indicate that AG alpha 1 encodes alpha-agglutinin. Features of the AG alpha 1 gene product suggest that the amino-terminal half of the protein contains the a-agglutinin binding domain and that the carboxy-terminal half contains a cell surface localization domain, possibly including a glycosyl phosphatidylinositol anchor.

scholarly journals RIG-I Mediates the Co-Induction of Tumor Necrosis Factor and Type I Interferon Elicited by Myxoma Virus in Primary Human Macrophages

2008 ◽  
Vol 4 (7) ◽  
pp. e1000099 ◽  
Author(s):  
Fuan Wang ◽  
Xiujuan Gao ◽  
John W. Barrett ◽  
Qing Shao ◽  
Eric Bartee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Type I Interferon ◽  
Myxoma Virus ◽  
Type I ◽  
Human Macrophages ◽  
Necrosis Factor

scholarly journals Efficient dengue virus (DENV) infection of human muscle satellite cells upregulates type I interferon response genes and differentially modulates MHC I expression on bystander and DENV-infected cells

2008 ◽  
Vol 89 (7) ◽  
pp. 1605-1615 ◽  
Author(s):  
Rajas V. Warke ◽  
Aniuska Becerra ◽  
Agatha Zawadzka ◽  
Diane J. Schmidt ◽  
Katherine J. Martin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Satellite Cells ◽  
Culture Medium ◽  
Type I Interferon ◽  
Denv Infection ◽  
Human Muscle ◽  
Type I ◽  
Mhc I ◽  
Muscle Satellite Cells ◽  
Infected Cells

Dengue virus (DENV) is a mosquito-borne flavivirus that causes an acute febrile disease in humans, characterized by musculoskeletal pain, headache, rash and leukopenia. The cause of myalgia during DENV infection is still unknown. To determine whether DENV can infect primary muscle cells, human muscle satellite cells were exposed to DENV in vitro. The results demonstrated for the first time high-efficiency infection and replication of DENV in human primary muscle satellite cells. Changes in global gene expression were also examined in these cells following DENV infection using Affymetrix GeneChip analysis. The differentially regulated genes belonged to two main functional categories: cell growth and development, and antiviral type I interferon (IFN) response genes. Increased expression of the type I IFN response genes for tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), melanoma-derived antigen 5 (MDA-5), IFN-γ-inducible protein 10 (IP-10), galectin 3 soluble binding protein (LGals3BP) and IFN response factor 7 (IRF7) was confirmed by quantitative RT-PCR. Furthermore, higher levels of cell-surface-bound intracellular adhesion molecule-1 (ICAM-1) and soluble ICAM-1 in the cell-culture medium were detected following DENV infection. However, DENV infection impaired the ability of the infected cells in the culture medium to upregulate cell-surface expression of MHC I molecules, suggesting a possible mechanism of immune evasion by DENV. The findings of this study warrant further clinical research to identify whether muscle cells are targets for DENV infection during the acute stage of the disease in vivo.

scholarly journals The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response

2018 ◽  
Author(s):  
Eugénie Bagdassarian ◽  
Virginie Doceul ◽  
Marie Pellerin ◽  
Antonin Demange ◽  
Léa Meyer ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Hepatitis E Virus ◽  
Type I Interferon ◽  
Hepatitis E ◽  
Terminal Region ◽  
Janus Kinase ◽  
Functional Domain ◽  
Type I ◽  
Amino Terminal ◽  
Stat Pathway

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the non-structural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and in particular the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. By contrast, MetPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent as MetPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.

scholarly journals A New Member of the S-Layer Protein Family: Characterization of the crs Gene fromCampylobacter rectus

1998 ◽  
Vol 66 (4) ◽  
pp. 1521-1526 ◽  
Author(s):  
Beinan Wang ◽  
Ellen Kraig ◽  
David Kolodrubetz
Keyword(s):  
Cell Surface ◽  
Consensus Sequence ◽  
Surface Protein ◽  
Single Copy ◽  
Periodontal Pathogen ◽  
Amino Terminal ◽  
Campylobacter Rectus ◽  
Length Polymorphisms ◽  
Its Gene ◽  
A Cell

ABSTRACT Strains of the periodontal pathogen Campylobacter rectus express a 150- to 166-kDa protein on their cell surface. This protein forms a paracrystalline lattice, called the surface layer (S-layer), on the outer membrane of this gram-negative bacterium. To initiate a genetic analysis of the function of the S-layer in the pathogenesis of C. rectus, we have cloned and characterized its gene. The S-layer gene (crs) from C. rectus314 encodes a cell surface protein which does not have a cleaved signal peptide at its amino terminus. Although the amino acid sequence deduced from the crs gene has 50% identity with the amino-terminal 30 amino acids of the four S-layer proteins from Campylobacter fetus, the similarity decreases to less than 16% over the rest of the protein. Thus, the crs gene from C. rectus encodes a novel S-layer protein whose precise role in pathogenesis may differ from that of S-layer proteins from other organisms. Southern and Northern blot analyses with probes from different segments of the crs gene indicate that the S-layer gene is a single-copy, monocistronic gene in C. rectus. RNA end mapping and sequence analyses were used to define the crs promoter; there is an exact match to theEscherichia coli −10 promoter consensus sequence but only a weak match to the −35 consensus element. Southern blots of DNA from another strain of C. rectus, ATCC 33238, demonstrated that the crs gene is also present in that strain but that there are numerous restriction fragment length polymorphisms in the second half of the gene. This finding suggests that the carboxy halves of the S-layer proteins from strains 314 and 33238 differ. It remains to be determined whether the diversities in sequence are reflected in functional or antigenic differences important for the pathogenesis of different C. rectus isolates.

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