bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue Specificity of the Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen (LANA/orf73) Promoter in Transgenic Mice
Authors: Jeong Joseph H. , Hines-Boykin Rebecca , Ash John D. , Dittmer Dirk P. 
Published: October 2002

ABSTRACT

Kaposi's sarcoma-associated herpesvirus
(KSHV/HHV-8) is a human-oncogenic herpesvirus. Cells from KSHV-associated tumors, such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), are of endothelial and B-cell origin, respectively. KSHV persists indefinitely in these cell lineages during latent infection. Indeed, cellular latency is a hallmark of all herpesviruses that is intimately linked to their pathogenesis. We previously characterized the promoter for the KSHV latency-associated nuclear antigen LANA/orf73. LANA is required for latent episome maintenance and has also been implicated in oncogenesis. Hence, regulation of LANA expression is critical to KSHV persistence. We find that a region extending to bp −1299 upstream of the LANA transcription start site is able to drive
lacZ
-reporter gene expression in several lines of transgenic mice. In agreement with KSHV's natural tropism, we detected reporter gene expression in CD19-positive B cells but not in CD3-positive T cells. We also detected expression in the kidney and, at a lower level, in the liver. In contrast to KS tumors, transgene expression was localized to kidney tubular epithelium rather than vascular endothelial cells. This suggests that our promoter fragment contains all
cis
-regulatory elements sufficient for B-cell specificity but not those required for endothelial specificity. Alternatively, while the
trans
-acting factors required for LANA expression in B cells are evolutionarily conserved, those that regulate endothelial cell-specific expression are unique to humans. Our in vivo studies address a conundrum in KSHV biology: in culture, KSHV is able to infect a variety of cell types indiscriminately, while in healthy latent carriers KSHV is found in B lymphocytes. The transgenic-mouse experiments reported here suggest that tissue-restricted LANA gene expression could explain B-cell-specific viral persistence.
Productive Infection of Plasmacytoid Dendritic Cells with Human Immunodeficiency Virus Type 1 Is Triggered by CD40 Ligation
Authors: Fong Lawrence , Mengozzi Manuela , Abbey Nancy W. , Herndier Brian G. , Engleman Edgar G. 
Published: October 2002

ABSTRACTImmature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), responsible for primary antiviral immunity. IPC express surface molecules CD4, CCR5, and CXCR4, which are known coreceptors required for human immunodeficiency virus (HIV) infection. Here we show that IPC are susceptible to and replicate HIV type 1 (HIV-1). Importantly, viral replication is triggered upon activation of IPC with CD40 ligand, a signal physiologically delivered by CD4 T cells. Immunohistochemical staining of tonsil from HIV-infected individuals reveals HIV p24+IPC, consistent with in vivo infection of these cells. IPC exposed in vitro to HIV produce alpha interferon, which partially inhibits viral replication. Nevertheless, IPC efficiently transmit HIV-1 to CD4 T-cells, and such transmission is also augmented by CD40 ligand activation. IPC produce RANTES/CCL5 and MIP-1α/CCL3 when exposed to HIV in vitro. IPC also induce naïve CD4 T cells to proliferate and would therefore preferentially infect these cells. These results indicate that IPC may play an important role in the dissemination of HIV.
Cooperative Activation of Human Papillomavirus Type 8 Gene Expression by the E2 Protein and the Cellular Coactivator p300
Authors: Müller Andreas , Ritzkowsky Andreas , Steger Gertrud 
Published: October 2002

ABSTRACT

The E2 proteins of papillomaviruses (PV) bind to the coactivator CBP/p300 as do many other transcription factors, but the precise role of CBP/p300 in E2-specific functions is not yet understood. We show that the E2 protein of human PV type 8 (HPV8) directly binds to p300. Activation of HPV8 gene expression by low amounts of HPV8 E2 was stimulated up to sevenfold by coexpression of p300. The interaction between E2 and p300 may play a role in differentiation-dependent activation of PV gene expression, since we can show that the expression level of p300 increases during keratinocyte differentiation. Surprisingly, sequence-specific binding of E2 to its recognition sites within the regulatory region of HPV8 is not necessary for this cooperation, indicating that E2 can be recruited to the promoter via protein-protein interaction. HPV8 E2 binds via its N-terminal activation domain (AD), its C-terminal DNA binding domain (DBD), and its internal hinge region to p300 in vitro
.
Transient-transfection assays revealed that the AD is necessary and sufficient for cooperative activation with p300. However, we provide evidence that the interaction of the hinge and the DBD of HPV8 E2 with p300 may contribute. Our data suggest an important role of p300 in regulation of HPV8 gene expression and reveal a new mechanism by which E2 may be recruited to a promoter to activate transcription without sequence specific DNA binding.
Inhibition of PACT-Mediated Activation of PKR by the Herpes Simplex Virus Type 1 Us11 Protein
Authors: Peters Gregory A. , Khoo David , Mohr Ian , Sen Ganes C. 
Published: October 2002

ABSTRACT
PACT, a protein activator of PKR, can cause inhibition of cellular protein synthesis and apoptosis. Here, we report that the Us11 protein of herpes simplex virus type 1 can block PKR activation by PACT both in vitro and in vivo. Although Us11 can bind to both PKR and PACT, mutational analyses revealed that the binding of Us11 to PKR, and not to PACT, was essential for its inhibitory action. Similar analyses also revealed that the inhibitory effect was mediated by an interaction between the C-terminal half of Us11 and the N-terminal domain of PKR. The binding of Us11 to PKR did not block the binding of PKR to PACT but prevented its activation. Us11 is the first example of a viral protein that can inhibit the action of PACT on PKR.
Systematic Assembly of a Full-Length Infectious cDNA of Mouse Hepatitis Virus Strain A59
Authors: Yount Boyd , Denison Mark R. , Weiss Susan R. , Baric Ralph S. 
Published: October 2002

ABSTRACT
A novel method was developed to assemble a full-length infectious cDNA of the group II coronavirus mouse hepatitis virus strain A59 (MHV-A59). Seven contiguous cDNA clones that spanned the 31.5-kb MHV genome were isolated. The ends of the cDNAs were engineered with unique junctions and assembled with only the adjacent cDNA subclones, resulting in an intact MHV-A59 cDNA construct of ∼31.5 kb in length. The interconnecting restriction site junctions that are located at the ends of each cDNA are systematically removed during the assembly of the complete full-length cDNA product, allowing reassembly without the introduction of nucleotide changes. RNA transcripts derived from the full-length MHV-A59 construct were infectious, although transfection frequencies were enhanced 10- to 15-fold in the presence of transcripts encoding the nucleocapsid protein N. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar growth kinetics, plaque morphology, and cytopathology in murine cells as did wild-type MHV-A59. Molecularly cloned viruses recognized the MHV receptor (MHVR) for docking and entry, and pretreatment of cells with monoclonal antibodies against MHVR blocked virus entry and replication. Cells infected with molecularly cloned MHV-A59 virus expressed replicase (gene 1) proteins identical to those of laboratory MHV-A59. Importantly, the molecularly cloned viruses contained three marker mutations that had been derived from the engineered component clones. Full-length infectious constructs of MHV-A59 will permit genetic modifications of the entire coronavirus genome, particularly in the replicase gene. The method has the potential to be used to construct viral, microbial, or eukaryotic genomes approaching several million base pairs in length and used to insert restriction sites at any given nucleotide in a microbial genome.
Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-κB and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies
Authors: Quivy Vincent , Adam Emmanuelle , Collette Yves , Demonte Dominique , Chariot Alain , Vanhulle Caroline , Berkhout Ben , Castellano Rémy , de Launoit Yvan , Burny Arsène , Piette Jacques , Bours Vincent , Van Lint Carine 
Published: October 2002

ABSTRACT
The transcription factor NF-κB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation, since treatment with deacetylase inhibitors such as trichostatin A (TSA) or sodium butyrate (NaBut) markedly induces HIV-1 transcriptional activity of the long terminal repeat (LTR) promoter. Here, we demonstrate that TSA (NaBut) synergized with both ectopically expressed p50/p65 and tumor necrosis factor alpha/SF2 (TNF)-induced NF-κB to activate the LTR. This was confirmed for LTRs from subtypes A through G of the HIV-1 major group, with a positive correlation between the number of κB sites present in the LTRs and the amplitude of the TNF-TSA synergism. Mechanistically, TSA (NaBut) delayed the cytoplasmic recovery of the inhibitory protein IκBα. This coincided with a prolonged intranuclear presence and DNA binding activity of NF-κB. The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression.
Evolution of Phenotypic Drug Susceptibility and Viral Replication Capacity during Long-Term Virologic Failure of Protease Inhibitor Therapy in Human Immunodeficiency Virus-Infected Adults
Authors: Barbour Jason D. , Wrin Terri , Grant Robert M. , Martin Jeffrey N. , Segal Mark R. , Petropoulos Christos J. , Deeks Steven G. 
Published: October 2002

ABSTRACT

Continued use of antiretroviral therapy despite the emergence of drug-resistant human immunodeficiency virus (HIV) has been associated with the durable maintenance of plasma HIV RNA levels below pretherapy levels. The factors that may account for this partial control of viral replication were assessed in a longitudinal observational study of 20 HIV-infected adults who remained on a stable protease inhibitor-based regimen despite ongoing viral replication (plasma HIV RNA levels consistently >500 copies/ml). Longitudinal plasma samples (
n
= 248) were assayed for drug susceptibility and viral replication capacity (measured by using a single-cycle recombinant-virus assay). The initial treatment-mediated decrease in plasma viremia was directly proportional to the reduction in replicative capacity (
P
= 0.01). Early virologic rebound was associated the emergence of a virus population exhibiting increased protease inhibitor phenotypic resistance, while replicative capacity remained low. During long-term virologic failure, plasma HIV RNA levels often remained stable or increased slowly, while phenotypic resistance continued to increase and replicative capacity decreased slowly. The emergence of primary genotypic mutations within protease (particularly V82A, I84V, and L90M) was temporally associated with increasing phenotypic resistance and decreasing replicative capacity, while the emergence of secondary mutations within protease was associated with more-gradual changes in both phenotypic resistance and replicative capacity. We conclude that HIV may be constrained in its ability to become both highly resistant and highly fit and that this may contribute to the continued partial suppression of plasma HIV RNA levels that is observed in some patients with drug-resistant viremia.
Differential Requirements for COPI Coats in Formation of Replication Complexes among Three Genera of
Picornaviridae
Authors: Gazina Elena V. , Mackenzie Jason M. , Gorrell Rebecca J. , Anderson David A. 
Published: October 2002

ABSTRACT
Picornavirus RNA replication requires the formation of replication complexes (RCs) consisting of virus-induced vesicles associated with viral nonstructural proteins and RNA. Brefeldin A (BFA) has been shown to strongly inhibit RNA replication of poliovirus but not of encephalomyocarditis virus (EMCV). Here, we demonstrate that the replication of parechovirus 1 (ParV1) is partly resistant to BFA, whereas echovirus 11 (EV11) replication is strongly inhibited. Since BFA inhibits COPI-dependent steps in endoplasmic reticulum (ER)-Golgi transport, we tested a hypothesis that different picornaviruses may have differential requirements for COPI in the formation of their RCs. Using immunofluorescence and cryo-immunoelectron microscopy we examined the association of a COPI component, β-COP, with the RCs of EMCV, ParV1, and EV11. EMCV RCs did not contain β-COP. In contrast, β-COP appeared to be specifically distributed to the RCs of EV11. In ParV1-infected cells β-COP was largely dispersed throughout the cytoplasm, with some being present in the RCs. These results suggest that there are differences in the involvement of COPI in the formation of the RCs of various picornaviruses, corresponding to their differential sensitivity to BFA. EMCV RCs are likely to be formed immediately after vesicle budding from the ER, prior to COPI association with membranes. ParV1 RCs are formed from COPI-containing membranes but COPI is unlikely to be directly involved in their formation, whereas formation of EV11 RCs appears to be dependent on COPI association with membranes.
Baculovirus Infection Raises the Level of TATA-Binding Protein That Colocalizes with Viral DNA Replication Sites
Authors: Quadt Ilja , Mainz Daniela , Mans Ruud , Kremer Andreas , Knebel-Mörsdorf Dagmar 
Published: October 2002

ABSTRACT

During the infection cycle of
Autographa californica
multicapsid nuclear polyhedrosis virus, the TATA-binding protein (TBP) of the insect host cell likely participates in early viral transcription, which is mediated by the host RNA polymerase II. However, the role of TBP in late and very late viral transcription, which is accomplished by an alpha-amanitin-resistant RNA polymerase, is unclear. We observed a dramatic increase of TBP protein during the late phases of infection. TBP mRNA levels, however, were not coordinately increased. Indirect-immunofluorescence studies revealed a nuclear redistribution of TBP during infection. After labeling of viral replication centers with bromodeoxyuridine (BrdU), costaining of TBP and BrdU showed that TBP localized to viral DNA replication centers. These results suggest a putative role of TBP during late viral transcription, which may occur in close proximity to viral DNA replication.
In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus
Authors: Mukhopadhyay Suchetana , Chipman Paul R. , Hong Eunmee M. , Kuhn Richard J. , Rossmann Michael G. 
Published: October 2002

ABSTRACT
In vitro-assembled core-like particles produced from alphavirus capsid protein and nucleic acid were studied by cryoelectron microscopy. These particles were found to have a diameter of 420 Å with 240 copies of the capsid protein arranged in a T=4 icosahedral surface lattice, similar to the nucleocapsid core in mature virions. However, when the particles were subjected to gentle purification procedures, they were damaged, preventing generation of reliable structural information. Similarly, purified nucleocapsid cores isolated from virus-infected cells or from mature virus particles were also of poor quality. This suggested that in the absence of membrane and glycoproteins, nucleocapsid core particles are fragile, lacking accurate icosahedral symmetry.
Implication of the Lymphocyte-Specific Nuclear Body Protein Sp140 in an Innate Response to Human Immunodeficiency Virus Type 1
Authors: Madani Navid , Millette Robert , Platt Emily J. , Marin Mariana , Kozak Susan L. , Bloch Donald B. , Kabat David 
Published: October 2002

ABSTRACT

The viral infectivity factor (Vif) of human immunodeficiency virus type 1 (HIV-1) neutralizes an unidentified antiviral pathway that occurs only in nonpermissive (NP) cells. Using a yeast two-hybrid screen of a human lymphocyte cDNA library, we identified several potential Vif partners. One, the nuclear body protein Sp140, was found specifically in all NP cells (
n
= 12 cell lines tested;
P
≤ 0.001), and HIV-1 infection induced its partial dispersal from nuclear bodies into cytosolic colocalization with Vif. Our results implicate Sp140 in a response to HIV-1 that may be related to or coordinated with the pathway that inactivates HIV-1 lacking
vif
.
Evidence for Early Infection of Nonneoplastic Natural Killer Cells by Epstein-Barr Virus
Authors: Trempat Pascal , Tabiasco Julie , Andre Pascale , Faumont Nathalie , Meggetto Fabienne , Delsol Georges , Gascoyne Randy D. , Fournie Jean-Jacques , Vivier Eric , Brousset Pierre 
Published: October 2002

ABSTRACTWe examined lymph nodes and tonsils from patients with infectious mononucleosis by combined detection of EBV-encoded RNA and a specific marker of natural killer (NK) cells, PEN5. A small number of Epstein-Barr virus (EBV) latently infected nonneoplastic NK cells were detected. Our data demonstrate that NK cells are natural targets of EBV and that infection of these cells is an early event observed during primary EBV infection.
Identification of the Hepatitis C Virus E2 Glycoprotein Binding Site on the Large Extracellular Loop of CD81
Authors: Drummer Heidi E. , Wilson Kirilee A. , Poumbourios Pantelis 
Published: October 2002

ABSTRACT

The binding of hepatitis C virus glycoprotein E2 to the large extracellular loop (LEL) of CD81 has been shown to modulate human T-cell and NK cell activity in vitro. Using random mutagenesis of a chimera of maltose-binding protein and LEL residues 113 to 201, we have determined that the E2-binding site on CD81 comprises residues Ile
182
, Phe
186
, Asn
184
, and Leu
162
. These findings reveal an E2-binding surface of approximately 806 Å
2
and potential target sites for the development of small-molecule inhibitors of E2 binding.
Comparative Analysis of Anti-Hepatitis C Virus Activity and Gene Expression Mediated by Alpha, Beta, and Gamma Interferons
Authors: Cheney I. Wayne , Lai Vicky C. H. , Zhong Weidong , Brodhag Tessa , Dempsey Shannon , Lim Charmaine , Hong Zhi , Lau Johnson Y. N. , Tam Robert C. 
Published: October 2002

ABSTRACTA direct comparison of the inhibitory effects of alpha, beta, and gamma interferons (IFNs) on replication of a hepatitis C virus subgenomic replicon in a hepatoma cell line revealed similarities in antiviral potency. However, alternate IFN-induced antiviral mechanisms were suggested following observations of striking differences between IFN-γ and IFN-α/β with respect to strength and durability of the antiviral response and the magnitude and pattern of IFN-mediated gene expression.
Identification of a Hepatitis B Virus Genome in Wild Chimpanzees (Pan troglodytes schweinfurthi) from East Africa Indicates a Wide Geographical Dispersion among Equatorial African Primates
Authors: Vartanian Jean-Pierre , Pineau Pascal , Henry Michel , Hamilton William D. , Muller Martin N. , Wrangham Richard W. , Wain-Hobson Simon 
Published: October 2002

ABSTRACTDNAs from four wild chimpanzees (Pan troglodytes schweinfurthi) from eastern Africa were screened for 14 DNA viruses and retroviruses. Between two and three viruses were found in each animal. An entire hepatitis B virus (HBV) genome was amplified and sequenced from samples taken from one animal. This indicates that HBV is distributed across the entire range of chimpanzee habitats.
Evidence for Regulation of Long Terminal Repeat Transcription by Wnt Transcription Factor TCF-4 in Human Astrocytic Cells
Authors: Wortman Bethany , Darbinian Nune , Sawaya Bassel E. , Khalili Kamel , Amini Shohreh 
Published: October 2002

ABSTRACT

The Wnt signaling pathway plays an important role in neural cell development and function. The key components of this pathway, β-catenin and its partner TCF-4/LEF-1, exert their effects on transcription by entering the nuclei, where they associate with the TCF-4/LEF-1 DNA motif positioned in the promoters of several important genes. Here we examined the role of TCF-4 upon transcription of the human immunodeficiency virus type 1 (HIV-1) promoter in human astrocytic cells. Our results showed that expression of TCF-4 in human astrocytic cells (U-87MG cells) decreased the basal and Tat-mediated transcription of the HIV-1 long terminal repeat (LTR). Results from promoter deletion studies revealed that the promoter sequence of the LTR with no classical binding motif for TCF-4/LEF-1, which spans positions −80 to +80 of the LTR, remained responsive to down-regulation by TCF-4. Noticeably, removal of the sequences between positions −80 and −68 decreased the negative effect of TCF-4 on viral gene transcription. A mutant variant of TCF-4 with no binding site for β-catenin was able to down-regulate LTR transcription, suggesting that β-catenin may not be directly involved in the observed regulatory events. Results from the glutathione
S
-transferase pull-down assay as well as the combined immunoprecipitation and Western blot analysis of protein extract from U-87MG cells revealed an interaction of Tat with TCF-4. Subcellular examination of TCF-4 and Tat in cells expressing either protein alone showed a predominantly nuclear accumulation of these proteins. However, in cells which coexpressed both TCF-4 and Tat, significant levels of these proteins were found in the cytoplasm. All together, these observations provide evidence for the cooperative interaction of TCF-4, the important transcription factor of the Wnt pathway, with Tat; this interaction may determine the level of viral gene transcription in human astrocytic cells.
The Influenza A Virus NS1 Protein Inhibits Activation of Jun N-Terminal Kinase and AP-1 Transcription Factors
Authors: Ludwig Stephan , Wang Xiuyan , Ehrhardt Christina , Zheng Hongyong , Donelan Nicola , Planz Oliver , Pleschka Stephan , García-Sastre Adolfo , Heins Gudrun , Wolff Thorsten 
Published: October 2002

ABSTRACT
The influenza A virus nonstructural NS1 protein is known to modulate host cell gene expression and to inhibit double-stranded RNA (dsRNA)-mediated antiviral responses. Here we identify NS1 as the first viral protein that antagonizes virus- and dsRNA-induced activation of the stress response-signaling pathway mediated through Jun N-terminal kinase.
Regions of Mouse Mammary Tumor Virus Superantigen Involved in Interaction with the Major Histocompatibility Complex Class II I-A Molecule
Authors: Wirth Susanne , Vessaz Annelyse , Krummenacher Claude , Baribaud Frédéric , Acha-Orbea Hans , Diggelmann Heidi 
Published: October 2002

ABSTRACT

To study the major histocompatibility complex class II I-E dependence of mouse mammary tumor virus (MMTV) superantigens, we constructed hybrids between the I-E-dependent MMTV(GR) and the I-E-independent
mtv
-
7
superantigens and tested them in vivo. Our results suggest that, although the C-terminal third mediates I-A interaction, additional binding sites are located elsewhere in the superantigen.