bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitination of Human T-Cell Leukemia Virus Type 1 Tax Modulates Its Activity
Authors: Peloponese Jean-Marie , Iha Hidekatsu , Yedavalli Venkat R. K. , Miyazato Akiko , Li Yan , Haller Kerstin , Benkirane Monsef , Jeang Kuan-Teh 
Published: October 2004

ABSTRACT
Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the genesis of adult T-cell leukemia, it is important to understand the processes which can activate or inactivate Tax function. Here, we report that ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax function. We show that ubiquitination does not target Tax for degradation by the proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form.
A Negative Regulatory Element (Base Pairs −204 to −177) of the EICP0 Promoter of Equine Herpesvirus 1 Abolishes the EICP0 Protein's
trans
-Activation of Its Own Promoter
Authors: Kim Seong K. , Albrecht Randy A. , O'Callaghan Dennis J. 
Published: October 2004

ABSTRACT

The early EICP0 protein is a powerful
trans
-activator that activates all classes of equine herpesvirus 1 (EHV-1) promoters but, unexpectedly,
trans
-activates its own promoter very weakly. Transient transfection assays that employed constructs harboring deletions within the EICP0 promoter indicated that EICP0
cis
-acting sequences within bp −224 to −158 relative to the first ATG abolished the EICP0 protein's
trans
-activation of its own promoter. When inserted into the promoters of other EHV-1 genes, this sequence also downregulated activation of the immediate-early IE(−169/+73), early thymidine kinase TK(−215/+97), and late glycoprotein K gK(−83/+14) promoters, indicating that the
cis
-acting sequence (−224 to −158) downregulated expression of representative promoters of all classes of EHV-1 genes and contains a negative regulatory element (NRE). To define the
cis
-acting element(s), three synthetic oligonucleotides (Na [bp −224 to −195], Nb [bp −204 to −177], and Nc [bp −185 to −156]) were synthesized and cloned upstream of the EICP0(−157/−21) promoter. Of the three synthetic sequences, only the Nb oligonucleotide caused the downregulation of the EICP0 promoter. The NRE was identified as a 28-bp element to lie at −204 to −177 that encompassed the sequence of ([−204]AGATACAGATGTTCGATAAATTGGAACC[−177]). Gel shift assays performed with mouse L-M, rabbit RK-13, and human HeLa cell nuclear extracts and γ-
32
P-labeled wild-type and mutant NREs demonstrated that a ubiquitous nuclear protein(s) (NRE-binding protein, NREBP) binds specifically to a sequence (bp −193 to −183) in the NRE. The NREBP is also present in the nucleus of EHV-1-infected cells; however, the amount of NREBP in EHV-1-infected L-M cells that bound to the Nb oligonucleotide was reduced compared to that in uninfected L-M cells. Transient transfection assays showed that deletions or mutations within the NREBP-binding site abolished the NRE activity of the EICP0 promoter. These results suggested that the NREBP may mediate the NRE activity of the EICP0 promoter and may function in the coordinate expression of EHV-1 genes.
Membrane Binding Properties and Terminal Residues of the Mature Hepatitis C Virus Capsid Protein in Insect Cells
Authors: Ogino Tomoaki , Fukuda Hiroyuki , Imajoh-Ohmi Shinobu , Kohara Michinori , Nomoto Akio 
Published: October 2004

ABSTRACT

The immature core protein (p23, residues 1 to 191) of hepatitis C virus undergoes posttranslational modifications including intramembranous proteolysis within its C-terminal signal sequence by signal peptide peptidase to generate the mature form (p21). In this study, we analyzed the cleavage site and other amino acid modifications that occur on the core protein. To produce the posttranslationally modified core protein, we used a baculovirus-insect cell expression model system. As previously reported, p23 is processed to form p21 in insect as well as in mammalian cells. p21 was found to be associated with the cytoplasmic membrane, and its significant portion behaved as an integral membrane protein. The protein was purified from the membrane by a simple and unique procedure on the basis of its membrane-binding properties and solubility in detergents. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of purified p21 showed that the average molecular mass (
m/z
19,307) of its single-charged ion differs by
m/z
1,457 from that calculated for p23. To determine the posttranslational modifications, tryptic p21 peptides were analyzed by MALDI-TOF MS. We found three peptides that did not match the theoretically derived peptides of p23. Analysis of these peptides by MALDI-TOF tandem MS revealed that they correspond to N-terminal peptides (residues 2 to 9 and 2 to 10) starting with α-
N
-acetylserine and C-terminal peptide (residues 150 to 177) ending with phenylalanine. These results suggest that the mature core protein (molecular mass of 19,306 Da) includes residues 2 to 177 and that its N terminus is blocked with an acetyl group.
The C-Mer Gene Is Induced by Epstein-Barr Virus Immediate-Early Protein BRLF1
Authors: Li Yuling , Mahajan Nupam P. , Webster-Cyriaque Jennifer , Bhende Prasanna , Hong Gregory K. , Earp H. Shelton , Kenney Shannon 
Published: October 2004

ABSTRACTBRLF1 (R) is one of two Epstein-Barr virus (EBV) immediate-early proteins that mediate the switch from the latent to the lytic form of viral replication. In this report, we show that R induces expression of the cellular C-mer gene in a variety of cell lines. C-mer expression was detected in lymphoblastoid cells immortalized with wild-type EBV but not in lymphoblastoid cells immortalized with an EBV that had BRLF1 deleted. Oral hairy leukoplakia tongue tissue, which contains the lytic form of EBV replication, also has enhanced C-mer expression. C-mer is a receptor tyrosine kinase activated by the ligand Gas6. C-mer is required for phagocytosis of apoptotic debris by monocytes/macrophages and retinal pigment epithelial cells and is capable of producing an antiapoptotic signal. Modulation of the C-mer signal transduction cascade by a variety of different approaches did not alter the ability of R to induce lytic EBV gene transcription. Therefore, C-mer activation may be important for some other aspect of lytic EBV infection.
Effects on Rotavirus Cell Binding and Infection of Monomeric and Polymeric Peptides Containing α2β1 and αxβ2 Integrin Ligand Sequences
Authors: Graham Kate L. , Zeng Weiguang , Takada Yoshikazu , Jackson David C. , Coulson Barbara S. 
Published: October 2004

ABSTRACT
Integrin-using rotaviruses bind MA104 cell surface α2β1 integrin via the Asp-Gly-Glu (DGE) sequence in virus spike protein VP4 and interact with αxβ2 integrin during cell entry through outer capsid protein VP7. Infection is inhibited by the α2β1 ligand Asp-Gly-Glu-Ala (DGEA) and the αxβ2 ligand Gly-Pro-Arg-Pro (GPRP), and virus-α2β1 binding is increased by α2β1 activation. In this study, we analyzed the effects of monomers and polymers containing DGEA-, GPRP-, and DGEA-related peptides on rotavirus binding and infection in intestinal (Caco-2) and kidney (MA104) cells and virus binding to recombinant α2β1. Blockade of rotavirus-cell binding and infection by peptides and anti-α2 antibody showed that Caco-2 cell entry is dependent on virus binding to α2β1 and interaction with αxβ2. At up to 0.5 mM, monomeric DGEA and DGAA inhibited binding to α2β1 and infection. At higher concentrations, DGEA and DGAA showed a reduced ability to inhibit virus-cell binding and infection that depended on virus binding to α2β1 but occurred without alteration in cell surface expression of α2, β2, or αvβ3 integrin. This loss of DGEA activity was abolished by genistein treatment and so was dependent on tyrosine kinase signaling. It is proposed that this signaling activated existing cell surface α2β1 to increase virus-cell attachment and entry. Polymeric peptides containing DGEA and GPRP or GPRP only were inhibitory to SA11 infection at approximately 10-fold lower concentrations than peptide monomers. As polymerization can improve peptide inhibition of virus-receptor interactions, this approach could be useful in the development of inhibitors of receptor recognition by other viruses.
Inhibition of Epstein-Barr Virus (EBV) Reactivation by Short Interfering RNAs Targeting p38 Mitogen-Activated Protein Kinase or c-mycin EBV-Positive Epithelial Cells
Authors: Gao Xiangrong , Wang Haoran , Sairenji Takeshi 
Published: October 2004

ABSTRACTLatent Epstein-Barr virus (EBV) is reactivated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in EBV-infected cells. In this study, we found that TPA up-regulated phosphorylation of p38, a mitogen-activated protein kinase, and activated c-mycmRNA in EBV-positive epithelial GT38 cells. The EBV immediate-early gene BZLF1 mRNA and its product ZEBRA protein were induced following TPA treatment. Protein kinase C inhibitors, 1-(5-isoquinolinesulphonyl)-2, 5-dimethylpiperazine (H7) and staurosporine, inhibited the induction of p38 phosphorylation and the activation of c-Myc by TPA. The p38 inhibitor SB203580 blocked both p38 phosphorylation and ZEBRA expression by TPA. Pretreatment of GT38 cells with the nitric oxide (NO) donorS-nitroso-N-acetylpenicillamine inhibited p38 phosphorylation and c-Myc activation by TPA, suggesting that NO may inhibit EBV reactivation via both p38 and c-Myc. By using short interfering RNA (siRNA) targeting either p38 or c-myc, we found that p38 or c-mycsiRNA specifically inhibited expression of the respective gene and also suppressed the induction of ZEBRA and EBV early antigen. The interferon (IFN)-responsive gene expression tests ruled out the possibility that the antiviral effect of siRNA is dependent on IFN. Our present study demonstrates for the first time that either p38 or c-mycsiRNA can efficiently inhibit TPA-induced EBV reactivation in GT38 cells, indicating that p38- and/or c-myc-associated signaling pathways may play critical roles in the disruption of EBV latency by TPA.
The Varicella-Zoster Virus Open Reading Frame 63 Latency-Associated Protein Is Critical for Establishment of Latency
Authors: Cohen Jeffrey I. , Cox Edward , Pesnicak Lesley , Srinivas Shamala , Krogmann Tammy 
Published: October 2004

ABSTRACT
Varicella-zoster virus (VZV) expresses at least six viral transcripts during latency. One of these transcripts, derived from open reading frame 63 (ORF63), is one of the most abundant viral RNAs expressed during latency. The VZV ORF63 protein has been detected in human and experimentally infected rodent ganglia by several laboratories. We have deleted >90% of both copies of the ORF63 gene from the VZV genome. Animals inoculated with the ORF63 mutant virus had lower mean copy numbers of latent VZV genomes in the dorsal root ganglia 5 to 6 weeks after infection than animals inoculated with parental or rescued virus, and the frequency of latently infected animals was significantly lower in animals infected with the ORF63 mutant virus than in animals inoculated with parental or rescued virus. In contrast, the frequency of animals latently infected with viral mutants in other genes that are equally or more impaired for replication in vitro, compared with the ORF63 mutant, is similar to that of animals latently infected with parental VZV. Examination of dorsal root ganglia 3 days after infection showed high levels of VZV DNA in animals infected with either ORF63 mutant or parental virus; however, by days 6 and 10 after infection, the level of viral DNA in animals infected with the ORF63 mutant was significantly lower than that in animals infected with parental virus. Thus, ORF63 is not required for VZV to enter ganglia but is the first VZV gene shown to be critical for establishment of latency. Since the present vaccine can reactivate and cause shingles, a VZV vaccine based on the ORF63 mutant virus might be safer.
Amino-Terminal Region of the Human Immunodeficiency Virus Type 1 Nucleocapsid Is Required for Human APOBEC3G Packaging
Authors: Luo Kun , Liu Bindong , Xiao Zuoxiang , Yu Yunkai , Yu Xianghui , Gorelick Robert , Yu Xiao-Fang 
Published: October 2004

ABSTRACT
APOBEC3G exerts its antiviral activity by targeting to retroviral particles and inducing viral DNA hypermutations in the absence of Vif. However, the mechanism by which APOBEC3G is packaged into virions remains unclear. We now report that viral genomic RNA enhances but is not essential for human APOBEC3G packaging into human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac, and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and intracellular Gag complexes was detected by equilibrium density and velocity sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was also detected by coimmunoprecipitation experiments. This interaction did not require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region, especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and APOBEC3G interaction and virion packaging. The linker region flanked by the two active sites of human APOBEC3G was also important for efficient packaging into HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular complexes was observed. These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging.
PCNA Interacts with Indian Mung Bean Yellow Mosaic Virus Rep and Downregulates Rep Activity
Authors: Bagewadi Basavaraj , Chen Shoajiang , Lal Sunil K. , Choudhury Nirupam Roy , Mukherjee Sunil K. 
Published: October 2004

ABSTRACTProliferative cell nuclear antigen (PCNA), a conserved plant protein as well as an important replication factor, is induced in response to geminivirus infection in the resting cells of the phloem tissues. The biochemical role of PCNA in rolling circle replication (RCR) of geminivirus DNA has not been explored in detail. The initiation of RCR of the bipartite genome of a geminivirus, Indian mung bean yellow mosaic virus (IMYMV), is mainly controlled by viral protein Rep (or AL1 or AC1). The role of host PCNA in RCR of IMYMV was revealed by studying the physical and functional interactions between recombinant PCNA and recombinant IMYMV Rep. Pea nuclear PCNA as well as recombinant pea PCNA showed binding to recombinant Rep in experiments involving both affinity chromatography and yeast two-hybrid approaches. The contacting amino acid residues of PCNA seemed to be present throughout a wide region of the trimeric protein, while those of Rep appeared to be localized only in the middle part of the protein. The site-specific nicking-closing activity and the ATPase function of IMYMV Rep were impaired by PCNA. These observations lead to interesting speculations about the control of viral RCR and dynamic profiles of protein-protein interactions at the RCR origin of the geminiviruses.
Cell Surface Delivery of the Measles Virus Nucleoprotein: a Viral Strategy To Induce Immunosuppression
Authors: Marie Julien C. , Saltel Frédéric , Escola Jean-Michel , Jurdic Pierre , Wild T. Fabian , Horvat Branka 
Published: October 2004

ABSTRACTAlthough only a few blood cells are infected during measles, this infectious disease is followed by acute immunosuppression, associated with high infant mortality. Measles virus nucleoprotein has been suggested to contribute to virus-induced inhibition of the immune response. However, it has been difficult to understand how this cytosolic viral protein could leave an infected cell and then perturb the immune response. Here we demonstrate that intracellularly synthesized nucleoprotein enters the late endocytic compartment, where it recruits its cellular ligand, the Fcγ receptor. Nucleoprotein is then expressed at the surfaces of infected leukocytes associated with the Fcγ receptor and is secreted into the extracellular compartment, allowing its interaction with uninfected cells. Finally, cell-derived nucleoprotein inhibits the secretion of interleukin-12 and the generation of the inflammatory reaction, both shown to be impaired during measles. These results reveal nucleoprotein egress from infected cells as a novel strategy in measles-induced immunosuppression.
Global Analysis of Host Cell Gene Expression Late during Cytomegalovirus Infection Reveals Extensive Dysregulation of Cell Cycle Gene Expression and Induction of Pseudomitosis Independent of US28 Function
Authors: Hertel Laura , Mocarski Edward S. 
Published: October 2004

ABSTRACT
Replication
of human cytomegalovirus (CMV) depends on host cell gene products
working in conjunction with viral functions and leads to a dramatic
dysregulation of cell cycle gene expression. Comprehensive
transcriptional profiling was used to identify pathways most
dramatically modulated by CMV at late times during infection and to
determine the extent to which expression of the viral chemokine
receptor US28 contributed to modulating cellular gene expression. Cells
infected with the AD169 strain of virus or a fully replication
competent US28-deficient derivative (RV101) were profiled throughout
the late phase of infection (50, 72, and 98 h postinfection).
Although sensitive statistical analysis showed striking global changes
in transcript levels in infected cells compared to uninfected cells,
the expression of US28 did not contribute to these alterations. CMV
infection resulted in lower levels of transcripts encoding
cytoskeletal, extracellular matrix, and adhesion proteins, together
with small GTPases and apoptosis regulators, and in higher
levels of transcripts encoding cell cycle, DNA replication, energy
production, and inflammation-related gene products. Surprisingly, a
large number of cellular transcripts encoding mitosis-related proteins
were upmodulated at late times in infection, and these were associated
with the formation of abnormal mitotic spindles and the appearance of
pseudomitotic cells. These data extend our understanding of how broadly
CMV alters the regulation of host cell cycle gene products and
highlight the establishment of a mitosis-like environment in the
absence of cellular DNA replication as important for viral replication
and
maturation.
APOBEC3G Incorporation into Human Immunodeficiency Virus Type 1 Particles
Authors: Zennou Véronique , Perez-Caballero David , Göttlinger Heinrich , Bieniasz Paul D. 
Published: October 2004

ABSTRACT
APOBEC3G is promiscuous with respect to its antiretroviral effect, requiring that it be packaged into diverse retrovirus particles. Here, we show that most virally encoded human immunodeficiency virus type 1 particle components are dispensable for APOPEC3G incorporation. However, replacement of the nucleocapsid (NC) Gag domain with a leucine zipper abolished APOBEC3G incorporation. Moreover, coprecipitation analysis showed that APOBEC3G-Gag interaction requires NC and nonspecific RNA. These observations suggest that APOBEC3G exploits an essential property of retroviruses, namely, RNA packaging, to infiltrate particles. Because it is, therefore, difficult to evolve specific sequences that confer escape from APOBEC3G, these findings may explain why lentiviruses evolved an activity that induces its destruction.
Differential Effects on the Hepatitis C Virus (HCV) Internal Ribosome Entry Site by Vitamin B12and the HCV Core Protein
Authors: Li Dongsheng , Lott William B. , Martyn John , Haqshenas Gholamreza , Gowans Eric J. 
Published: October 2004

ABSTRACTTo investigate the role of the hepatitis C virus internal ribosome entry site (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES elements were constructed to contain the reciprocal domain IV in the otherwise HCV and classical swine fever virus IRES elements. This permitted an examination of the role of domain IV in the control of HCV translation. A specific inhibitor of the HCV IRES, vitamin B12, was shown to inhibit translation directed by all IRES elements which contained domain IV from the HCV and the GB virus B IRES elements, whereas the HCV core protein could only suppress translation from the wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin B12and the core protein differ, and they target different regions of the IRES.
QUANTUM DENSITY OF PROBABILITY AT THE CLASSICAL PECULIAR POINT
Authors: BUONANNO L. , RENNA M. , PAVLOTSKY I.P. 
Published: October 2004

The so-called no-interaction theorem of D.G. Currie, T.F. Jordan, E.C. Sudarshan, H. Leutwyler, G. Marmo and N. Mukunda makes it possible to construct relativistic quasi-classical particle dynamics in the post-Galilean approximation only.1−4 In this approximation the Lagrangians are singular on some surfaces of the phase space. The dynamical properties are essentially peculiar on the singular surfaces.5−8 In the particular case of the rectilinear motion of two electrons the peculiar point appears when the distance between the particles r=r0, where r0=e2/mc2 (the so-called “radius of an electron”). Here m and e are respectively the mass and the charge of the electron, c is the speed of light. In this paper it is shown that in the simple case of a one-dimensional system of two electrons with the symmetrical initial condition v1=−v2 (v1 and v2 are the velocities of the particles), the density of probability tends to zero when the distance between electrons tends to r0. In other words, the point of the classical phase-space, which cannot be crossed by the trajectory of the system, reflects at the point where the corresponding quantum system has the vanishing probability.
PHENOMENOLOGICAL THEORY OF THE DIELECTRIC RESPONSE OF LEAD MAGNESIUM NIOBATE AND LEAD SCANDIUM TANTALATE
Authors: QIAN H. , BURSILL L.A. 
Published: October 2004

The influence of the random field effects originating from charged chemical defects and nano-domain textures on the formation and dynamics of polar clusters is analyzed. The spatial distribution of the local fields is not totally random but contains some correlations in direction and strength. Polar clusters are classified to be dynamic or frozen according to their dynamic characteristics in the random fields. The relaxation formula of a dipolar moment in an anisotropic double-well potential is deduced. Two percolation models are introduced, one to account for frustration effects associated with multiple orientations of polar clusters, which results in a broad diffuse dielectric response and the second to account for the case whereby there may be a phase transition to a ferroelectric state. The dielectric permittivity and dissipation factor of the typical relaxors lead magnesium niobate and lead scandium tantalate are predicted as a function of both temperature and frequency, which results are in good agreement with the experimental measurements.