bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Proinflammatory Cytokine Expression by Herpes Simplex Virus Type 1
Authors: Mogensen Trine H. , Melchjorsen Jesper , Malmgaard Lene , Casola Antonella , Paludan Søren R. 
Published: May 2004

ABSTRACTViral immune evasion strategies are important for establishment and maintenance of infections. Many viruses are in possession of mechanisms to counteract the antiviral response raised by the infected host. Here we show that a herpes simplex virus type 1 (HSV-1) mutant lacking functional viral protein 16 (VP16)—a tegument protein promoting viral gene expression—induced significantly higher levels of proinflammatory cytokines than wild-type HSV-1. This was observed in several cell lines and primary murine macrophages, as well as in peritoneal cells harvested from mice infected in vivo. The enhanced ability to stimulate cytokine expression in the absence of VP16 was not mediated directly by VP16 but was dependent on the viral immediate-early genes for infected cell protein 4 (ICP4) and ICP27, which are expressed in a VP16-dependent manner during primary HSV infection. The virus appeared to target cellular factors other than interferon-induced double-stranded RNA-activated protein kinase R (PKR), since the virus mutants remained stronger inducers of cytokines in cells stably expressing a dominant-negative mutant form of PKR. Finally, mRNA stability assay revealed a significantly longer half-life for interleukin-6 mRNA after infection with the VP16 mutant than after infection with the wild-type virus. Thus, HSV is able to suppress expression of proinflammatory cytokines by decreasing the stability of mRNAs, thereby potentially impeding the antiviral host response to infection.
Processing of a Pestivirus Protein by a Cellular Protease Specific for Light Chain 3 of Microtubule-Associated Proteins
Authors: Fricke Jens , Voss Christiane , Thumm Michael , Meyers Gregor 
Published: May 2004

ABSTRACTThe genome of the cytopathogenic (cp) bovine viral diarrhea virus (BVDV) JaCP contains a cellular insertion coding for light chain 3 (LC3) of microtubule-associated proteins, the mammalian homologue of yeast Aut7p/Apg8p. The cellular insertion induces cp BVDV-specific processing of the viral polyprotein by a cellular cysteine protease homologous to the known yeast protease Aut2p/Apg4p. Three candidate bovine protease genes were identified on the basis of the sequence similarity of their products with theSaccharomyces cerevisiaeenzyme. The search for a system for functional testing of these putative LC3-specific proteases revealed that the components involved in this processing have been highly conserved during evolution, so that the substrate derived from a mammalian virus is processed in cells of mammalian, avian, fish, and insect origin, as well as in rabbit reticulocyte lysate, but not in wheat germ extracts. Moreover, two of these proteases and a homologous protein from chickens were able to rescue the defect of a yeastAUT2deletion mutant. In coexpression experiments with yeast and wheat germ extracts one of the bovine proteases and the corresponding enzyme from chickens were able to process the viral polyprotein containing LC3. Northern blots showed that bovine viral diarrhea virus infection of cells has no significant influence on the expression of either LC3 or its protease, bAut2B2. However, LC3-specific processing of the viral polyprotein containing the cellular insertion is essential for replication of the virus since mutants with changes in the LC3 insertion significantly affecting processing at the LC3/NS3 site were not viable.
Intracellular Targeting Signals Contribute to Localization of Coronavirus Spike Proteins near the Virus Assembly Site
Authors: Lontok Erik , Corse Emily , Machamer Carolyn E. 
Published: May 2004

ABSTRACT
Coronavirus budding at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) requires accumulation of the viral envelope proteins at this point in the secretory pathway. Here we demonstrate that the spike (S) protein from the group 3 coronavirus infectious bronchitis virus (IBV) contains a canonical dilysine endoplasmic reticulum retrieval signal (-KKXX-COOH) in its cytoplasmic tail. This signal can retain a chimeric reporter protein in the ERGIC and when mutated allows transport of the full-length S protein as well as the chimera to the plasma membrane. Interestingly, the IBV S protein also contains a tyrosine-based endocytosis signal in its cytoplasmic tail, suggesting that any S protein that escapes the ERGIC will be rapidly endocytosed when it reaches the plasma membrane. We also identified a novel dibasic motif (-KXHXX-COOH) in the cytoplasmic tails of S proteins from group 1 coronaviruses and from the newly identified coronavirus implicated in severe acute respiratory syndrome. This dibasic motif also retained a reporter protein in the ERGIC, similar to the dilysine motif in IBV S. The cytoplasmic tails of S proteins from group 2 coronaviruses lack an intracellular localization signal. The inherent differences in S-protein trafficking could point to interesting variations in pathogenesis of coronaviruses, since increased levels of surface S protein could promote syncytium formation and direct cell-to-cell spread of the infection.
The Level of Virus-Specific T-Cell and Macrophage Recruitment in Porcine Reproductive and Respiratory Syndrome Virus Infection in Pigs Is Independent of Virus Load
Authors: Xiao Zhengguo , Batista Laura , Dee Scott , Halbur Patrick , Murtaugh Michael P. 
Published: May 2004

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) is the most important infectious disease agent of pigs worldwide, causing reproductive failure in pregnant sows and respiratory problems in nursing and growing pigs. PRRSV infection is characterized by a prolonged viremia of 30 or more days and an extended persistent infection of lymphoid tissues. To better understand the immunological basis for prolonged acute and persistent PRRSV infection, we have examined the cell-mediated immune (CMI) response throughout the course of infection and compared the results to the local distribution and abundance of PRRSV in infected tissues. PRRSV-specific T cells, enumerated by gamma interferon enzyme-linked immunospot assay, did not appear until 2 weeks after PRRSV inoculation, and their abundance exhibited substantial variation over time and among animals. In all cases the T-cell response was transient. High levels of viral RNA were present in lymphoid tissues of all animals in the acute phase of infection. Viral loads were decreased 1,000-fold or more in persistent infections, with the primary sites of persistence being tonsil, sternal lymph node, and inguinal lymph node. The abundance of virus-specific T cells in either acutely or persistently infected animals was highly variable and showed no correlation to the level of virus in lymphoid tissues. No significant difference in antigen-specific T-cell abundance was observed in secondary lymphoid tissues in either acute or persistent infection except for tonsil, in which the number of responding cells was extremely low. CD4+- and CD8+-T-cell frequencies did not change after PRRSV infection, though a decrease in γδ T cells was observed. Macrophages, the permissive cell type for PRRSV, were present in various levels in all tissue preparations and were not in proportion to local virus load. These findings indicate that a weak CMI response contributes to prolonged PRRSV infection and suggests that PRRSV suppresses T-cell recognition of infected macrophages. Thus, the slow but eventual resolution of PRRSV infection may be dependent on limiting permissive macrophages and on innate immune factors.
Mutational Analyses of Epstein-Barr Virus Glycoprotein 42 Reveal Functional Domains Not Involved in Receptor Binding but Required for Membrane Fusion
Authors: Silva Amanda L. , Omerović Jasmina , Jardetzky Theodore S. , Longnecker Richard 
Published: May 2004

ABSTRACT
Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with malignancies of both epithelial and lymphoid origin. Efficient infection of the latent host reservoir B lymphocytes involves the binding of glycoproteins gp350/220 for initial attachment, followed by the concerted action of gH, gL, gB, and gp42 for membrane fusion. The type II membrane protein gp42 is required for infection of B cells and assembles into a complex with gH and gL. The cellular host receptor for gp42, class II human leukocyte antigen (HLA), has been structurally verified by crystallization analyses of gp42 bound to HLA-DR1. Interestingly, the crystal structure revealed a hydrophobic pocket consisting of many aromatic and aliphatic residues from the predicted C-type lectin domain of gp42 that in other members of the C-type lectin family binds major histocompatibility complex class I or other diverse ligands. Although the hydrophobic pocket does not bind HLA class II, mutational analyses presented here indicate that this domain is essential for EBV-induced membrane fusion. In addition, mutational analysis of the region of gp42 contacting HLA class II in the gp42-HLA-DR1 cocrystal confirms that this region interacts with HLA class II and that this interaction is also important for EBV-induced membrane fusion.
Cleavage between Replicase Proteins p28 and p65 of Mouse Hepatitis Virus Is Not Required for Virus Replication
Authors: Denison Mark R. , Yount Boyd , Brockway Sarah M. , Graham Rachel L. , Sims Amy C. , Lu XiaoTao , Baric Ralph S. 
Published: May 2004

ABSTRACT

The p28 and p65 proteins of mouse hepatitis virus (MHV) are the most amino-terminal protein domains of the replicase polyprotein. Cleavage between p28 and p65 has been shown to occur in vitro at cleavage site 1 (CS1),
247
Gly↓Val
248
, in the polyprotein. Although critical residues for CS1 cleavage have been mapped in vitro, the requirements for cleavage have not been studied in infected cells. To define the determinants of CS1 cleavage and the role of processing at this site during MHV replication, mutations and deletions were engineered in the replicase polyprotein at CS1. Mutations predicted to allow cleavage at CS1 yielded viable virus that grew to wild-type MHV titers and showed normal expression and processing of p28 and p65. Mutant viruses containing predicted noncleaving mutations or a CS1 deletion were also viable but demonstrated delayed growth kinetics, reduced peak titers, decreased RNA synthesis, and small plaques compared to wild-type controls. No p28 or p65 was detected in cells infected with predicted noncleaving CS1 mutants or the CS1 deletion mutant; however, a new protein of 93 kDa was detected. All introduced mutations and the deletion were retained during repeated virus passages in culture, and no phenotypic reversion was observed. The results of this study demonstrate that cleavage between p28 and p65 at CS1 is not required for MHV replication. However, proteolytic separation of p28 from p65 is necessary for optimal RNA synthesis and virus growth, suggesting important roles for these proteins in the formation or function of viral replication complexes.
Intracellular Topology and Epitope Shielding of Poliovirus 3A Protein
Authors: Choe Sunny S. , Kirkegaard Karla 
Published: May 2004

ABSTRACT
The poliovirus RNA replication complex comprises multiple viral and possibly cellular proteins assembled on the cytoplasmic surface of rearranged intracellular membranes. Viral proteins 3A and 3AB perform several functions during the poliovirus replicative cycle, including significant roles in rearranging membranes, anchoring the viral polymerase to these membranes, inhibiting host protein secretion, and possibly providing the 3B protein primer for RNA synthesis. During poliovirus infection, the immunofluorescence signal of an amino-terminal epitope of 3A-containing proteins is markedly shielded compared to 3A protein expressed in the absence of other poliovirus proteins. This is not due to luminal orientation of all or a subset of the 3A-containing polypeptides, as shown by immunofluorescence following differential permeabilization and proteolysis experiments. Shielding of the 3A epitope is more pronounced in cells infected with wild-type poliovirus than in cells with temperature-sensitive mutant virus that contains a mutation in the 3D polymerase coding region adjacent to the 3AB binding site. Therefore, it is likely that direct binding of the poliovirus RNA-dependent RNA polymerase occludes the amino terminus of 3A-containing polypeptides in the RNA replication complex.
Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity
Authors: Lum Julian J. , Schnepple David J. , Nie Zilin , Sanchez-Dardon Jaime , Mbisa Georgina L. , Mihowich Jennifer , Hawley Nanci , Narayan Shanil , Kim John E. , Lynch David H. , Badley Andrew D. 
Published: May 2004

ABSTRACTThe ability of interleukin-7 (IL-7) and IL-15 to expand and/or augment effector cell functions may be of therapeutic benefit to human immunodeficiency virus (HIV)-infected patients. The functional effects of these cytokines on innate HIV-specific immunity and their impact on cells harboring HIV are unknown. We demonstrate that both IL-7 and IL-15 augment natural killer (NK) function by using cells (CD3−CD16+CD56+) from both HIV-positive and -negative donors. Whereas IL-7 enhances NK function through upregulation of Fas ligand, the effect of IL-15 is mediated through upregulation of tumor necrosis factor-related apoptosis-inducing ligand. The difference in these effector mechanisms is reflected by the ability of IL-15-treated but not IL-7-treated NK cells to reduce the burden of replication-competent HIV in autologous peripheral blood mononuclear cells (PBMC) (infectious units per million for control NK cells, 6.79; for IL-7-treated NK cells, 236.17; for IL-15-treated cells, 1.01;P= 0.01 versus control). In addition, the treatment of PBMC with IL-15-treated but not IL-7-treated NK cells causes undetectable HIV p24 (five of five cases), HIV RNA (five of five cases), or HIV DNA (three of five cases). These results support the concept of adjuvant immunotherapy of HIV infection with either IL-7 or IL-15 but suggest that the NK-mediated antiviral effect of IL-15 may be superior.
Reverse Genetic Analysis of the Transcription Regulatory Sequence of the Coronavirus Transmissible Gastroenteritis Virus
Authors: Curtis Kristopher M. , Yount Boyd , Sims Amy C. , Baric Ralph S. 
Published: May 2004

ABSTRACT
Coronavirus discontinuous transcription uses a highly conserved sequence (CS) in the joining of leader and body RNAs. Using a full-length infectious construct of transmissable gastroenteritis virus, the present study demonstrates that subgenomic transcription is heavily influenced by upstream flanking sequences and supports a mechanism of transcription attenuation that is regulated in part by a larger domain composed of primarily upstream flanking sequences which select appropriately positioned CS elements for synthesis of subgenomic RNAs.
Path Integration Deficits during Linear Locomotion after Human Medial Temporal Lobectomy
Authors: Philbeck John W. , Behrmann Marlene , Levy Lucien , Potolicchio Samuel J. , Caputy Anthony J. 
Published: May 2004

AbstractAnimal navigation studies have implicated structures in and around the hippocampal formation as crucial in performing path integration (a method of determining one's position by monitoring internally generated self-motion signals). Less is known about the role of these structures for human path integration. We tested path integration in patients who had undergone left or right medial temporal lobectomy as therapy for epilepsy. This procedure removed approximately 50% of the anterior portion of the hippocampus, as well as the amygdala and lateral temporal lobe. Participants attempted to walk without vision to a previously viewed target 2–6 m distant. Patients with right, but not left, hemisphere lesions exhibited both a decrease in the consistency of path integration and a systematic underregistration of linear displacement (and/or velocity) during walking. Moreover, the deficits were observable even when there were virtually no angular acceleration vestibular signals. The results suggest that structures in the medial temporal lobe participate in human path integration when individuals walk along linear paths and that this is so to a greater extent in right hemisphere structures than left. This information is relevant for future research investigating the neural substrates of navigation, not only in humans (e.g., functional neuroimaging and neuropsychological studies), but also in rodents and other animals.
Direct Current Stimulation over V5 Enhances Visuomotor Coordination by Improving Motion Perception in Humans
Authors: Antal Andrea , Nitsche Michael A. , Kruse Wolfgang , Kincses Tamás Z. , Hoffmann Klaus-Peter , Paulus Walter 
Published: May 2004

Abstract
The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subject's perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.
ERPs Reflect Lexical Identification in Word Fragment Priming
Authors: Friedrich Claudia K. , Kotz Sonja A. , Friederici Angela D. , Gunter Thomas C. 
Published: May 2004

Abstract
Behavioral evidence suggests that spoken word recognition involves the temporary activation of multiple entries in a listener's mental lexicon. This phenomenon can be demonstrated in cross-modal word fragment priming (CMWP). In CMWP, an auditory word fragment (prime) is immediately followed by a visual word or pseudoword (target). Experiment 1 investigated ERPs for targets presented in this paradigm. Half of the targets were congruent with the prime (e.g., in the prime-target pair: AM-AMBOSS [anvil]), half were not (e.g., AM-PENSUM [pensum]). Lexical entries of the congruent targets should receive activation from the prime. Thus, lexical identification of these targets should be facilitated. An ERP effect named P350, two frontal negative ERP deflections, and the N400 were sensitive to prime-target congruency. In Experiment 2, the relation of the formerly observed ERP effects to processes in a modality-independent mental lexicon was investigated by presenting primes visually. Only the P350 effect could be replicated across different fragment lengths. Therefore, the P350 is discussed as a correlate of lexical identification in a modality-independent mental lexicon.
Neurobiological Evidence for Abstract Phonological Representations in the Mental Lexicon during Speech Recognition
Authors: Eulitz Carsten , Lahiri Aditi 
Published: May 2004

Abstract
A central issue in speech recognition is how contrastive phonemic information is stored in the mental lexicon. The conventional view assumes that this information is closely related to acoustic properties of speech. Considering that no word is ever pronounced alike twice and that the brain has limited capacities to manage information, an opposing view proposes abstract underspecified representations where not all phonemic features are stored. We examined this proposal using event-related brain potentials, in particular mismatch negativity (MMN), an automatic change detection response in the brain that is sensitive to language-specific phoneme representations. In the current study, vowel pairs were presented to subjects, reversed as standard and deviant. Models not assuming underspecification predict equal MMNs for vowel pairs regardless of the reversal. In contrast, enhanced and earlier MMNs were observed for those conditions where the standard is not phonologically underspecified in the mental representation. This provides the first neurobiological evidence for a featurally underspecified mental lexicon.
Probing the Prerequisites for Motion Blindness
Authors: Niedeggen Michael , Hesselmann Guido , Sahraie Arash , Milders Maarten , Blakemore Colin 
Published: May 2004

Abstract
Neurobiological studies of visual awareness usually focus on the neural events elicited by perceived or nonperceived stimuli but neglect the preexisting conditions that allow (or prevent) conscious perception. We have examined the conditions that lead to temporary motion blindness in a rapid serial visual presentation paradigm, in which subjects have to detect coherent motion in the peripheral stream after a cue (a red fixation point) in the central stream. The failure of awareness depends critically on the occurrence of similar coherent motion events (probes) before the cue. Event-related brain potentials (ERPs) were recorded to track the processing of motion distractors, which determine the prerequisites for this transient deficit. Analysis of motion-evoked responses revealed that there is no progressive reduction in sensitivity in early visual processing. There is, however, a progressive increase in amplitude of a negative wave over the frontal cortex at approximately 250 msec after motion onset and a corresponding reduction of a centro-parietal positivity at approximately 350 msec with an increasing number of distractors. We propose that these nonsensory ERP components reflect a postperceptual frontal gating mechanism that controls the access of visual stimuli to higher order evaluation and conscious detection.
Event-related Brain Potentials Elicited by Morphological, Homographic, Orthographic, and Semantic Priming
Authors: Domínguez Alberto , de Vega Manuel , Barber Horacio 
Published: May 2004

Abstract
The morphological structure of words, in terms of their stem morphemes and affixes, could influence word access and representation in lexical memory. Three experiments were carried out to explore the attributes of event-related potentials evoked by different types of priming. Morphological priming, with pairs of words related by their stem (hijo/hija [son/ daughter]), produced a sustained attenuation (and even a tendency to positivity) of the N400 shown by unrelated words across the three experiments. Homographic priming (Experiment 1), using pairs of words with a superficially similar stem, but without morphological or semantic relation (foco/foca [floodlight/seal]), produced an initial attenuation similar to the morphological pairs, but which rapidly tended to form a delayed N400, due to the impossibility of integration. However, orthographic priming (rasa/rana [flat/frog]) in Experiment 2 does not produce attenuation of the N400 but an effect similar to that of unrelated pairs. Experiment 3 shows that synonyms advance more slowly than morphological pairs to meaning coherence, but finally produce a more positive peak around 600 msec.