bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent Contributions of Polyomavirus Middle T and Small T to the Regulation of Early and Late Gene Expression and DNA Replication
Authors: Chen Li , Wang Xiaoyu , Fluck Michele M. 
Published: July 2006

ABSTRACTWe previously showed that murine polyomavirus mutants that lack both middle T (MT) and small T (ST) functions have a severe pleiotropic defect in early and late viral gene expression as well as genome amplification. The respective contribution of MT and ST to this phenotype was unclear. This work separates the roles of MT and ST in both permissive mouse cells and nonpermissive rat cells. It demonstrates for the first time a role for both proteins. To gain insight into the signaling pathways that might be required, we focused on MT and its mutants. The results show that each of the major MT signaling connections, Shc, phosphatidylinositol 3′-kinase, and phospholipase C γ1, could contribute in an additive way. Unexpectedly, a mutant lacking all these connections because the three major tyrosines had been converted to phenylalanine retained some activity. A mutant in which all six MT C-terminal tyrosines had been mutated was inactive. This suggests a novel signaling pathway for MT that uses the minor tyrosines. What is common to ST and the individual MT signaling pathways is the ability to signal to the polyomavirus enhancer, in particular to the crucial AP-1 and PEA3/ets binding sites. This connection explains the pleiotropy of MT and ST effects on transcription and DNA replication.
Mouse Cytomegalovirus Crosses the Species Barrier with Help from a Few Human Cytomegalovirus Proteins
Authors: Tang Qiyi , Maul Gerd G. 
Published: July 2006

ABSTRACT
Strong species specificity and similar tropisms suggest mouse cytomegalovirus (mCMV) as a potential vector for transgenes into human cells. We reexamined the dogma that mouse cytomegalovirus cannot productively replicate in human cells and found that mouse cytomegalovirus can produce infectious particles albeit at a level that does not sustain an infection. This finding demonstrates that mouse cytomegalovirus can undergo all processes of its life cycle in human cells but may not be well adapted to circumvent the human cell's intrinsic defenses. The suppression of mCMV production in human cells is affected at several levels, which additively or synergistically result in the appearance of species specificity. Hydrolysis of most newly replicated viral DNA and very low capsid protein transcription reduced the potential particle production to insignificant levels. These effects can be ameliorated by adding human cytomegalovirus tegument proteins and immediate-early protein 1. They function synergistically to produce significant amounts of mCMV in human cells. While the possibility that mouse cytomegalovirus might replicate in human cells raises caution in the use of this virus as a transgene vector, manipulation of the mouse cytomegalovirus genome to allow limited spread to other human cells might also provide an advantage for the distribution of certain transgenic products.
Serial Passage through Human Glioma Xenografts Selects for a Δγ
1
34.5 Herpes Simplex Virus Type 1 Mutant That Exhibits Decreased Neurotoxicity and Prolongs Survival of Mice with Experimental Brain Tumors
Authors: Shah Amish C. , Price Kathleen H. , Parker Jacqueline N. , Samuel Sharon L. , Meleth Sreelatha , Cassady Kevin A. , Yancey Gillespie G. , Whitley Richard J. , Markert James M. 
Published: July 2006

ABSTRACT

Previous studies have described in vitro serial passage of a Δγ
1
34.5 herpes simplex virus type 1 (HSV-1) strain in SK-N-SH neuroblastoma cells and selection of mutants that have acquired the ability to infect and replicate in this previously nonpermissive cell line. Here we describe the selection of a mutant HSV-1 strain by in vivo serial passage, which prolongs survival in two separate experimental murine brain tumor models. Two conditionally replication-competent Δγ
1
34.5 viruses, M002, which expresses murine interleukin-12, and its parent virus, R3659, were serially passaged within human malignant glioma D54-MG cell lines in vitro or flank tumor xenografts in vivo. The major findings are (i) viruses passaged in vivo demonstrate decreased neurovirulence, whereas those passaged in vitro demonstrate a partial recovery of the neurovirulence associated with HSV-1; and (ii) vvD54-M002, the virus selected after in vivo serial passage of M002 in D54-MG tumors, improves survival in two independent murine brain tumor models compared to the parent (unpassaged) M002. Additionally, in vitro-passaged, but not in vivo-passaged, M002 displayed changes in the protein synthesis profile in previously nonpermissive cell lines, as well as early U
S
11 transcription. Thus, a mutant HSV-1 strain expressing a foreign gene can be selected for enhanced antitumor efficacy via in vivo serial passage within flank D54-MG tumor xenografts. The enhanced antitumor efficacy of vvD54-M002 is not due to restoration of protein synthesis or early U
S
11 expression. This finding emphasizes the contribution of the in vivo tumor environment for selecting novel oncolytic HSV specifically adapted for tumor cell destruction in vivo.
Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling
Authors: Santos Claudio R. , Blanco Sandra , Sevilla Ana , Lazo Pedro A. 
Published: July 2006

ABSTRACT
Viruses have to adjust to the host cell to guarantee their life cycle and survival. This aspect of the virus-host cell interaction is probably performed by viral proteins, such as serine-threonine kinases, that are present early during infection. Vaccinia virus has an early Ser-Thr kinase, B1R, which, although required for successful viral infection, is poorly characterized regarding its effects on cellular proteins, and thus, its potential contribution to pathogenesis is not known. Signaling by mitogen-activated protein kinase (MAPK) is mediated by the assembly of complexes between these kinases and the JIP scaffold proteins. To understand how vaccinia virus B1R can affect the host, its roles in the cellular signaling by MAPK complexes and c-Jun activation have been studied. Independently of its kinase activity, B1R can interact with the central region of the JIP1 scaffold protein. The B1R-JIP1 complex increases the amount of MAPK bound to JIP1; thus, MKK7 and TAK1 either bind with higher affinity or bind more stably to JIP1, while there is an increase in the phosphorylation state of JNK bound to JIP1. The functional consequence of these more stable interactions is an increase in the activity of transcription factors, such as c-Jun, that respond to these complexes. Furthermore, B1R is also able to directly phosphorylate c-Jun in residues different from those targeted by JNK and, thus, B1R can also cooperate by an independent route in c-Jun activation. Vaccinia virus B1R can thus modulate the signaling of pathways that respond to cellular stress.
Kinetics of Influenza A Virus Infection in Humans
Authors: Baccam Prasith , Beauchemin Catherine , Macken Catherine A. , Hayden Frederick G. , Perelson Alan S. 
Published: July 2006

ABSTRACTCurrently, little is known about the viral kinetics of influenza A during infection within an individual. We utilize a series of mathematical models of increasing complexity, which incorporate target cell limitation and the innate interferon response, to examine influenza A virus kinetics in the upper respiratory tracts of experimentally infected adults. The models were fit to data from an experimental H1N1 influenza A/Hong Kong/123/77 infection and suggest that it is important to include the eclipse phase of the viral life cycle in viral dynamic models. Doing so, we estimate that after a delay of ∼6 h, infected cells begin producing influenza virus and continue to do so for ∼5 h. The average lifetime of infected cells is ∼11 h, and the half-life of free infectious virus is ∼3 h. We calculated the basic reproductive number,R0, which indicated that a single infected cell could produce ∼22 new productive infections. This suggests that antiviral treatments have a large hurdle to overcome in moderating symptoms and limiting infectiousness and that treatment has to be initiated as early as possible. For about 50% of patients, the curve of viral titer versus time has two peaks. This bimodal behavior can be explained by incorporating the antiviral effects of interferon into the model. Our model also compared well to an additional data set on viral titer after experimental infection and treatment with the neuraminidase inhibitor zanamivir, which suggests that such models may prove useful in estimating the efficacies of different antiviral therapies for influenza A infection.
Autoactivation of the Epstein-Barr Virus Oncogenic Protein LMP1 during Type II Latency through Opposite Roles of the NF-κB and JNK Signaling Pathways
Authors: Goormachtigh Gautier , Ouk Tan-Sothéa , Mougel Alexandra , Tranchand-Bunel Denis , Masy Eric , Le Clorennec Christophe , Feuillard Jean , Bornkamm Georg W. , Auriault Claude , Manet Evelyne , Fafeur Véronique , Adriaenssens Eric , Coll Jean 
Published: July 2006

ABSTRACT
Epstein-Barr virus (EBV) is associated with several human malignancies where it expresses limited subsets of latent proteins. Of the latent proteins, latent membrane protein 1 (LMP1) is a potent transforming protein that constitutively induces multiple cell signaling pathways and contributes to EBV-associated oncogenesis. Regulation of LMP1 expression has been extensively described during the type III latency of EBV. Nevertheless, in the majority of EBV-associated tumors, the virus is commonly found to display a type II latency program in which it is still unknown which viral or cellular protein is really involved in maintaining LMP1 expression. Here, we demonstrate that LMP1 activates its own promoter pLMP1 through the JNK signaling pathway emerging from the TES2 domain. Our results also reveal that this activation is tightly controlled by LMP1, since pLMP1 is inhibited by LMP1-activated NF-κB signaling pathway. By using our physiological models of EBV-infected cells displaying type II latency as well as lymphoblastoid cell lines expressing a type III latency, we also demonstrate that this balanced autoregulation of LMP1 is shared by both latency programs. Finally, we show that this autoactivation is the most important mechanism to maintain LMP1 expression during the type II latency program of EBV.
Entry of Feline Calicivirus Is Dependent on Clathrin-Mediated Endocytosis and Acidification in Endosomes
Authors: Stuart Amanda D. , Brown T. David K. 
Published: July 2006

ABSTRACT

Feline calicivirus is a major causative agent of respiratory disease in cats. It is also one of the few cultivatable members of
Caliciviridae
. We have examined the entry process of feline calicivirus (FCV). An earlier study demonstrated that acidification in endosomes may be required. We have confirmed this observation and expanded upon it, demonstrating, using drugs to inhibit the various endocytic pathways and dominant-negative mutants, that FCV infects cells via clathrin-mediated endocytosis. We have also observed that FCV permeabilizes cell membranes early during infection to allow the coentry of toxins such as α-sarcin. Inhibitors of endosome acidification such as chloroquine and bafilomycin A1 blocked this permeabilization event, demonstrating that acidification is required for uncoating of the genome and access to the cytoplasm.
Intramolecular and Intermolecular Uridylylation by Poliovirus RNA-Dependent RNA Polymerase
Authors: Richards Oliver C. , Spagnolo Jeannie F. , Lyle John M. , Vleck Susan E. , Kuchta Robert D. , Kirkegaard Karla 
Published: July 2006

ABSTRACT

The 22-amino-acid protein VPg can be uridylylated in solution by purified poliovirus 3D polymerase in a template-dependent reaction thought to mimic primer formation during RNA amplification in infected cells. In the cell, the template used for the reaction is a hairpin RNA termed 2C-
cre
and, possibly, the poly(A) at the 3′ end of the viral genome. Here, we identify several additional substrates for uridylylation by poliovirus 3D polymerase. In the presence of a 15-nucleotide (nt) RNA template, the poliovirus polymerase uridylylates other polymerase molecules in an intermolecular reaction that occurs in a single step, as judged by the chirality of the resulting phosphodiester linkage. Phosphate chirality experiments also showed that VPg uridylylation can occur by a single step; therefore, there is no obligatory uridylylated intermediate in the formation of uridylylated VPg. Other poliovirus proteins that could be uridylylated by 3D polymerase in solution were viral 3CD and 3AB proteins. Strong effects of both RNA and protein ligands on the efficiency and the specificity of the uridylylation reaction were observed: uridylylation of 3D polymerase and 3CD protein was stimulated by the addition of viral protein 3AB, and, when the template was poly(A) instead of the 15-nt RNA, the uridylylation of 3D polymerase itself became intramolecular instead of intermolecular. Finally, an antiuridine antibody identified uridylylated viral 3D polymerase and 3CD protein, as well as a 65- to 70-kDa host protein, in lysates of virus-infected human cells.
Induction of the Early Growth Response 1 Gene by Epstein-Barr Virus Lytic Transactivator Zta
Authors: Chang Yao , Lee Heng-Huan , Chen Yu-Te , Lu Jean , Wu Shih-Yi , Chen Chaio-Wei , Takada Kenzo , Tsai Ching-Hwa 
Published: July 2006

ABSTRACT
Early growth response 1 (Egr-1) is a cellular transcription factor involved in diverse biologic functions. Egr-1 has been associated with Epstein-Barr virus (EBV) infection, but it is still unknown whether any EBV protein regulates Egr-1 expression. In this study, we first showed that EBV reactivation is involved in upregulation of Egr-1 and that Egr-1 can be induced by Zta, an EBV lytic transactivator. Zta not only binds to the Egr-1 promoter but also activates the ERK signaling pathway to trigger binding of Elk-1 to the Egr-1 promoter. In addition, knockdown of Egr-1 significantly reduces the spontaneous expression of Zta and Rta in EBV-infected 293 cells, suggesting that a positive-feedback network involving Egr-1 is required for EBV reactivation. This study also implies that Zta has the potential to affect expression of certain genes through Egr-1.
Identification of Essential Host Factors Affecting Tombusvirus RNA Replication Based on the Yeast Tet Promoters Hughes Collection
Authors: Jiang Yi , Serviene Elena , Gal Jozsef , Panavas Tadas , Nagy Peter D. 
Published: July 2006

ABSTRACT

To identify essential host genes affecting replication of
Tomato bushy stunt virus
(TBSV), a small model plant virus, we screened 800 yeast genes present in the yeast Tet promoters Hughes Collection. In total, we have identified 30 new host genes whose down-regulation either increased or decreased the accumulation of a TBSV replicon RNA. The identified essential yeast genes are involved in RNA transcription/metabolism, protein metabolism/transport, or other cellular processes. Detailed analysis of the effects of some of the identified yeast genes revealed that they might affect RNA replication by altering (i) the amounts/functions of p33 and p92
pol
viral replication proteins, (ii) the standard 10 to 20:1 ratio between p33 and p92
pol
in the viral replicase, (iii) the activity of the tombusvirus replicase, and (iv) the ratio of plus- versus minus-stranded RNA replication products. Altogether, this and previous genetic screening of yeast (Panavas et al., Proc. Natl. Acad. Sci. USA
102:
7326-7331, 2005) led to the identification of 126 host genes (out of ∼5,600 genes that represent ∼95% of all the known and predicted yeast genes) that affected the accumulation of tombusvirus RNA.
Expression of CCL20 and Granulocyte-Macrophage Colony-Stimulating Factor, but Not Flt3-L, from Modified Vaccinia Virus Ankara Enhances Antiviral Cellular and Humoral Immune Responses
Authors: Chavan R. , Marfatia K. A. , An I. C. , Garber D. A. , Feinberg M. B. 
Published: July 2006

ABSTRACTWhile modified vaccinia virus Ankara (MVA) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases, its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts. In light of recent data demonstrating that vaccinia viruses, including MVA, preferentially infect antigen-presenting cells (APCs) that play crucial roles in generating antiviral immunity, we hypothesized that expression of specific cytokines and chemokines that mediate APC recruitment and activation from recombinant MVA (rMVA) vectors would enhance the immunogenicity of these vectors. To test this hypothesis, we generated rMVAs that express murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), human CCL20/human macrophage inflammatory protein 3α (hCCL20/hMIP-3α), or human fms-like tyrosine kinase 3 ligand (hFlt3-L), factors predicted to increase levels of dendritic cells (DCs), to recruit DCs to sites of immunization, or to promote maturation of DCs in vivo, respectively. These rMVAs also coexpress the well-characterized, immunodominant lymphocytic choriomeningitis virus nucleoprotein (NP) antigen that enabled sensitive and quantitative assessment of antigen-specific CD8+T-cell responses following immunization of BALB/c mice. Our results demonstrate that immunization of mice with rMVAs expressing mGM-CSF or hCCL20, but not hFlt3-L, results in two- to fourfold increases of cellular immune responses directed against vector-encoded antigens and 6- to 17-fold enhancements of MVA-specific antibody titers, compared to those responses elicited by nonadjuvanted rMVA. Of note, cytokine augmentation of cellular immune responses occurs when rMVAs are given as primary immunizations but not when they are used as booster immunizations, suggesting that these APC-modulating proteins, when used as poxvirus-encoded adjuvants, are more effective at stimulating naïve T-cell responses than in promoting recall of preexisting memory T-cell responses. Our results demonstrate that a strategy to express specific genetic adjuvants from rMVA vectors can be successfully applied to enhance the immunogenicity of MVA-based vaccines.
Expression of the polycomb-group geneBMI1is related to an unfavourable prognosis in primary nodal DLBCL
Authors: van Galen Joost C , Muris Jettie J F , Oudejans Joost J , Vos Wim , Giroth Cindy P E , Ossenkoppele Gert J , Otte Arie P , Raaphorst Frank M , Meijer Chris J L M 
Published: July 2006

Background:: Clinical outcome in patients with diffuse large B cell lymphomas (DLBCL) is highly variable and poorly predictable. Microarray studies showed that patients with DLBCL with a germinal centre B cell-like (GCB) phenotype have a better prognosis than those with an activated B cell-like (ABC) phenotype. TheBMI1proto-oncogene was identified as one of the genes present in the signature of the ABC type of DLBCL, associated with a poor prognosis.Objectives:: (1) To investigate, in primary nodal DLBCL, the expression ofBMI1and its association with clinical outcome and DLBCL signature; (2) to look for an association betweenBMI1expression and the expression of its putative downstream targetsp14ARFandp16INK4a.Results::BMI1expression was found to be associated with poor clinical outcome, but not clearly with an ABC-like phenotype of DLBCL. Expression ofBMI1was frequently, but not always, related to low levels of expression ofp14ARFandp16INK4a.Conclusion:: Expression ofBMI1is associated with an unfavourable clinical outcome of primary nodal DLBCL.
Gastric duodenal metaplasia in duodenal adenomas
Authors: Rubio C A 
Published: July 2006

Backgound:In cases of known aetiology, gastric duodenal metaplasia (GMD) is a reversible lesion. In cases of unknown aetiology, the fate of GMD remains elusive. GMD was recently found in a duodenal adenoma.Aim:To audit the frequency of GMD occurring in a cohort of duodenal adenomas.Methods:Filed H&E-stained sections from 306 consecutive duodenal adenomas were investigated for the presence of GMD.Results:68% of the adenomas (n = 208) were from patients with familial adenomatous polyposis (FAP), and the remaining 32% (n = 98) were sporadic. GMD was found in 31.7% (66/208) of the duodenal FAP adenomas and in 59.2% (58/98) of the duodenal sporadic adenomas (p<0.05). The causes for this difference are elusive.Conclusions:As for other metaplasias of the gastrointestinal tract (intestinal metaplasia of the oesophagus and of the stomach, and metaplastic–hyperplastic polyposis of the colon, known to antedate neoplastic transformation), a subset of GMDs of unknown cause might be present in the duodenal mucosa before adenomatous changes ensue. That subset of GMD might have neoplastic proclivity similar to the metaplastic epithelium in other organs of the gastrointestinal tract. The known carcinogenic effect of high concentrations of bile acids and pancreatic juices bathing the duodenal mucosa carrying an irreversible subset of GDM might set aflame the adenomatous neoplastic transformation in these patients.
Cytology of chordoid meningioma: a series of five cases with emphasis on differential diagnoses
Authors: Lui Philip C W , Chau Tony K F , Wong Steve S , Lau Patrick P L , Tse Gary M K , Thomas Teresa M M , Ng Ho Keung 
Published: July 2006

Background:Chordoid meningioma is a rare meningioma variant characterised by epithelioid cord-like tumour cells in a myxoid stroma. It is classified as grade II (World Health Organization) tumours, as they have a tendency to behave more aggressively than traditional meningiomas and have a greater likelihood of recurrence.Aims:To report the features of intraoperative imprint smears of five cases of chordoid meningioma.Methods:The intraoperative squash smears were reviewed for cellularity, cellular atypia, mitotic figure, cytoplasmic vacuolation, intranuclear inclusion, presence of a cohesive cord of tumour cells, whorl-like structure, psammoma bodies, chronic inflammatory cells (lymphocytes and plasma cells), background mucin and necrosis.Results:All cases were of moderate to high cellularity, with cohesive cords of bland tumour cells possessing uniformly round nuclei with smooth nuclear outline, stippled chromatin and small nucleoli, with cytoplasmic vacuolation and chronic inflammatory cells in the background. Intranuclear inclusions (80%) and whorl-like structures (60%) were also common. Necrotic background, psammoma bodies or mitotic figures were consistently absent.Conclusions:The cytological features of chordoid mengiomas are distinctive, and intraoperative imprint diagnosis is feasible.
Dissociating Verbal and Nonverbal Conceptual Processing in the Human Brain
Authors: Thierry Guillaume , Price Cathy J. 
Published: July 2006

Abstract
Functional neuroimaging has highlighted a left-hemisphere conceptual system shared by verbal and nonverbal processing despite neuropsychological evidence that the ability to recognize verbal and nonverbal stimuli can doubly dissociate in patients with left- and right-hemisphere lesions, respectively. Previous attempts to control for perceptual differences between verbal and nonverbal stimuli in functional neuroimaging studies may have hidden differences arising at the conceptual level. Here we used a different approach and controlled for perceptual confounds by looking for amodal verbal and nonverbal conceptual activations that are common to both the visual and auditory modalities. In addition to the left-hemisphere conceptual system activated by all meaningful stimuli, we observed the left/right double dissociation in verbal and nonverbal conceptual processing, predicted by neuropsychological studies. Left middle and superior temporal regions were selectively more involved in comprehending words—heard or read—and the right midfusiform and right posterior middle temporal cortex were selectively more involved in making sense of environmental sounds and images. Thus, the neuroanatomical basis of a verbal/nonverbal conceptual processing dissociation is established.