bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uterine artery Doppler velocimetry for the detection of adverse obstetric outcomes in patients with elevated mid‐trimester β‐human chorionic gonadotrophin
Authors: Barkehall‐Thomas Andrea , Wilson Catherine , Baker Lesleigh , Bhuinneain Meabh ni , Wallace Euan M. 
Published: July 2005

Aim.  The aim of this study is to review the clinical usefulness of Doppler velocimetry of the uterine artery for the detection of adverse obstetric outcome in a population of women with elevated mid‐trimester serum β‐human chorionic gonadotrophin (βhCG).Methods.  Women with an unexplained elevated mid‐trimester βhCG level (≥ 4.0 multiples of the median) are offered uterine artery Doppler assessment at 22–24 weeks of gestation. We have audited the clinical usefulness of this practice by reviewing the prevalence of the adverse outcomes of gestational hypertension, intrauterine growth restriction (IUGR) and preterm birth and the predictive capacity of the test when applied to this subgroup of high‐risk patients.Results.  Sixty‐two women had an elevated serum βhCG and underwent Doppler study of uterine artery flow velocity waveform. Notching afforded better predictive utility for any outcome than the resistance index alone or in combination with notching. For a composite adverse outcome of any or all of gestational hypertension, birthweight ≤ 10th centile, and preterm delivery, the presence of a uterine notch alone had sensitivity of 30.7% and specificity of 93.8%. For the identification of severe fetal growth restriction (< 5th centile) and/or preeclampsia, the presence of a notch offered a sensitivity of 50%, specificity of 96.3%, a positive likelihood ratio of 13.5, and a negative likelihood ratio of 0.5.Conclusions.  The identification of uterine artery notching by means of Doppler ultrasound as a component of the surveillance of women with unexplained elevated βhCG levels significantly improves the prediction of preeclampsia and/or severe IUGR, although the low prevalence of 13% of these adverse outcomes limits the usefulness of the test in routine clinical practice.
The Distal Short Consensus Repeats 1 and 2 of the Membrane Cofactor Protein CD46 and Their Distance from the Cell Membrane Determine Productive Entry of Species B Adenovirus Serotype 35
Authors: Fleischli Christoph , Verhaagh Sandra , Havenga Menzo , Sirena Dominique , Schaffner Walter , Cattaneo Roberto , Greber Urs F. , Hemmi Silvio 
Published: July 2005

ABSTRACTThe human regulator of complement activation membrane cofactor protein (CD46) has recently been identified as an attachment receptor for most species B adenoviruses (Ads), including Ad type 3 (Ad3), Ad11, and Ad35, as well as species D Ad37. To characterize the interaction between Ad35 and CD46, hybrid receptors composed of different CD46 short consensus repeat (SCR) domains fused to immunoglobulin-like domains of CD4 and a set of 36 CD46 mutants containing semiconservative changes of single amino acids within SCR domains I and II were tested in binding and in Ad35-mediated luciferase transduction assays. In addition, anti-CD46 antibodies and soluble polypeptides constituting various CD46 domains were used in binding inhibition studies. Our data indicate that (i) CD46 SCR I or SCR II alone confers low but significant Ad35 binding; (ii) the presence of SCR I and II is required for optimal binding and transgene expression; (iii) transduction efficiencies equivalent to that of full-length CD46 are obtained if SCR I and II are at an appropriate distance from the cell membrane; (iv) ablation of the N-glycan attached to SCR I has no influence on receptor function, whereas ablation of the SCR II N-glycan results in about a two- to threefold reduction of binding and transgene expression; (v) most putative Ad35 binding residues are located on the same solvent-exposed face of the SCR I or SCR II domain, which are twisted by about 90°; and (vi) the putative Ad35 binding sites partly overlap with the measles virus binding surface.
Phosphorylation of Bluetongue Virus Nonstructural Protein 2 Is Essential for Formation of Viral Inclusion Bodies
Authors: Modrof Jens , Lymperopoulos Kostas , Roy Polly 
Published: July 2005

ABSTRACT
In bluetongue virus (BTV)-infected cells, large cytoplasmic aggregates are formed, termed viral inclusion bodies (VIBs), which are believed to be the sites of viral replication and morphogenesis. The BTV nonstructural protein NS2 is the major component of VIBs. NS2 undergoes intracellular phosphorylation and possesses a strong single-stranded RNA binding activity. By changing phosphorylated amino acids to alanines and aspartates, we have mapped the phosphorylated sites of NS2 to two serine residues at positions 249 and 259. Since both of these serines are within the context of protein kinase CK2 recognition signals, we have further examined if CK2 is involved in NS2 phosphorylation by both intracellular colocalization and an in vitro phosphorylation assay. In addition, we have utilized the NS2 mutants to determine the role of phosphorylation on NS2 activities. The data obtained demonstrate that NS2 phosphorylation is not necessary either for its RNA binding properties or for its ability to interact with the viral polymerase VP1. However, phosphorylated NS2 exhibited VIB formation while unmodified NS2 failed to assemble as VIBs although smaller oligomeric forms of NS2 were readily formed. Our data reveal that NS2 phosphorylation controls VIBs formation consistent with a model in which NS2 provides the matrix for viral assembly.
High-Potency Human Immunodeficiency Virus Vaccination Leads to Delayed and Reduced CD8
+
T-Cell Expansion but Improved Virus Control
Authors: Davenport Miles P. , Zhang Lei , Bagchi Ansuman , Fridman Arthur , Fu Tong-Ming , Schleif William , Shiver John W. , Ribeiro Ruy M. , Perelson Alan S. 
Published: July 2005

ABSTRACT

CD8
+
T lymphocytes are thought to play an important role in the control of acute and chronic human immunodeficiency virus infections. However, there is a significant delay between infection and the first observed increase in virus-specific CD8
+
T-cell numbers. Prior to this time, viral kinetics are not significantly different between controls and vaccinees. Surprisingly, higher initial virus-specific CD8
+
T-cell numbers lead to a longer delay prior to initial CD8
+
T-cell expansion, and slower CD8
+
T-cell increases. Nevertheless, higher initial CD8
+
T-cell numbers were associated with reduced peak and chronic viral loads and reduced CD4
+
T-cell depletion.
The Immediate-Early Protein IE0 of the
Autographa californica
Nucleopolyhedrovirus Is Not Essential for Viral Replication
Authors: Liqun Lu , Rivkin Hadassah , Chejanovsky Nor 
Published: July 2005

ABSTRACT

The role of the
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) immediate-early protein IE0 in the baculoviral infection is not clear. In this study, we constructed the recombinant virus vAcΔie0 null for
ie0
expression by targeted mutagenesis replacing
exon0
with the
cat
gene. We found that vAcΔie0 replicated efficiently in
Spodoptera littoralis
SL2 cells, which are poorly permissive for AcMNPV. In contrast, in
Spodoptera frugiperda
SF9 cells, which are fully permissive for AcMNPV, vAcΔie0 DNA replication and budded virus production were delayed. These results and recently published data (X. Dai et al., J. Virol.
78:
9633-9644, 2004) indicate that
ie0
is not essential for AcMNPV replication but enhances it in permissive SF9 cells.
Identification of Two New HLA-A*1101-Restricted Tax Epitopes Recognized by Cytotoxic T Lymphocytes in an Adult T-Cell Leukemia Patient after Hematopoietic Stem Cell Transplantation
Authors: Harashima Nanae , Tanosaki Ryuji , Shimizu Yukiko , Kurihara Kiyoshi , Masuda Takao , Okamura Jun , Kannagi Mari 
Published: July 2005

ABSTRACTWe previously reported that Tax-specific CD8+cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo.
Identification of Secret Agent as the
O-
GlcNAc Transferase That Participates in Plum Pox Virus Infection
Authors: Chen D. , Juárez S. , Hartweck L. , Alamillo J. M. , Simón-Mateo C. , Pérez J. J. , Fernández-Fernández M. R. , Olszewski N. E. , García J. A. 
Published: July 2005

ABSTRACT

Serine and threonine of many nuclear and cytoplasmic proteins are posttranslationally modified with O-linked
N
-acetylglucosamine (
O
-GlcNAc). This modification is made by O-linked
N
-acetylglucosamine transferases (OGTs). Genetic and biochemical data have demonstrated the existence of two OGTs of
Arabidopsis thaliana
, SECRET AGENT (SEC) and SPINDLY (SPY), with at least partly overlapping functions, but there is little information on their target proteins. The N terminus of the capsid protein (CP) of
Plum pox virus
(PPV) isolated from
Nicotiana clevelandii
is
O
-GlcNAc modified. We show here that
O-
GlcNAc modification of PPV CP also takes place in other plant hosts,
N. benthamiana
and
Arabidopsis
. PPV was able to infect the
Arabidopsis
OGT mutants
sec-1
,
sec-2
, and
spy-3
, but at early times of the infection, both rate of virus spread and accumulation were reduced in
sec-1
and
sec-2
relative to
spy-3
and wild-type plants. By matrix-assisted laser desorption ionization-time of flight mass spectrometry, we determined that a 39-residue tryptic peptide from the N terminus of CP of PPV purified from the
spy-3
mutant, but not
sec-1
or
sec-2
, was
O
-GlcNAc modified, suggesting that SEC but not SPY modifies the capsid. While our results indicate that
O-
GlcNAc modification of PPV CP by SEC is not essential for infection, they show that the modification has a role(s) in the process.
Morphological and Molecular Characterization of a Cypovirus (
Reoviridae
) from the Mosquito
Uranotaenia sapphirina
(Diptera: Culicidae)
Authors: Shapiro Alexandra , Green Terry , Rao Shujing , White Susan , Carner Gerry , Mertens Peter P. C. , Becnel James J. 
Published: July 2005

ABSTRACT

A novel cypovirus has been isolated from the mosquito
Uranotaenia sapphirina
(UsCPV) and shown to cause a chronic infection confined to the cytoplasm of epithelial cells of the gastric ceca and posterior stomach. The production of large numbers of virions and inclusion bodies and their arrangement into paracrystalline arrays gives the gut of infected insects a distinctive blue iridescence. The virions, which were examined by electron microscopy, are icosahedral (55 to 65 nm in diameter) with a central core that is surrounded by a single capsid layer. They are usually packaged individually within cubic inclusion bodies (polyhedra, ∼100 nm across), although two to eight virus particles were sometimes occluded together. The virus was experimentally transmitted per os to several mosquito species. The transmission rate was enhanced by the presence of magnesium ions but was inhibited by calcium ions. Most of the infected larvae survived to adulthood, and the adults retained the infection. Electrophoretic analysis of the UsCPV genome segments (using 1% agarose gels) generated a migration pattern (electropherotype) that is different from those of the 16
Cypovirus
species already recognized. UsCPV genome segment 10 (Seg-10) showed no significant nucleotide sequence similarity to the corresponding segment of the other cypoviruses that have previously been analyzed, and it has different “conserved” termini. A BLAST search of the UsCPV deduced amino acid sequence also showed little similarity to
Antheraea mylitta
CPV-4 (67 of 290 [23%]) or
Choristoneura fumiferana
CPV-16 (33 of 111 [29%]). We conclude that UsCPV should be recognized as a member of a new
Cypovirus
species (Cypovirus 17, strain UsCPV-17).
Humoral Immune Response Recognizes a Complex Set of Epitopes on Human Papillomavirus Type 6 L1 Capsomers
Authors: Orozco Johnnie J. , Carter Joseph J. , Koutsky Laura A. , Galloway Denise A. 
Published: July 2005

ABSTRACT
Although epitope mapping has identified residues on the human papillomavirus (HPV) major capsid protein (L1) that are important for binding mouse monoclonal antibodies, epitopes recognized by human antibodies are not known. To map epitopes on HPV type 6 (HPV6) L1, surface-exposed loops were mutated to the corresponding sequence of HPV11 L1. HPV6 L1 capsomers had one to six regions mutated, including the BC, DE, EF, FG, and HI loops and the 139 C-terminal residues. After verifying proper conformation, hybrid capsomers were used in enzyme-linked immunosorbent assays with 36 HPV6-seropositive sera from women enrolled in a study of incident HPV infection. Twelve sera were HPV6 specific, while the remainder reacted with both HPV6 and HPV11 L1. By preadsorption studies, 6/11 of these sera were shown to be cross-reactive. Among the HPV6-specific sera there was no immunodominant epitope recognized by all sera. Six of the 12 sera recognized epitopes that contained residues from combinations of the BC, DE, and FG loops, one serum recognized an epitope that consisted partially of the C-terminal arm, and three sera recognized complex epitopes to which reactivity was eliminated by switching all five loops. Reactivity in two sera was not eliminated even with all six regions swapped. The patterns of epitope recognition did not change over time in women whose sera were examined 9 years after their first-seropositive visit.
Determination of Interactions between Tegument Proteins of Herpes Simplex Virus Type 1
Authors: Vittone Valerio , Diefenbach Eve , Triffett Damian , Douglas Mark W. , Cunningham Anthony L. , Diefenbach Russell J. 
Published: July 2005

ABSTRACT

The aim of this study was to elucidate protein-protein interactions between tegument proteins of herpes simplex virus type 1 (HSV-1). To do so, we have cloned and expressed in the LexA yeast (
Saccharomyces cerevisiae
) two-hybrid system, 13 of the 21 currently known tegument proteins of HSV-1. These included the tegument proteins essential for replication in cell lines, UL17, UL36, UL37, UL48, and UL49, and the nonessential tegument proteins US11, UL11, UL14, UL16, UL21, UL41, UL46, and UL47. A total of 104 combinations were screened in the yeast two-hybrid assay, with 9 interactions identified. These included: UL11-UL16, UL36-UL37, UL36-UL48, UL46-UL48, UL47-UL48, and UL48-UL49. The remaining interactions consisted of self-associations that were observed for US11, UL37, and UL49. The interactions UL36-UL37, UL36-UL48, UL37-UL37, UL46-UL48, and UL47-UL48 have not been previously reported for HSV-1. The interaction of UL46-UL48 was verified using an in vitro pull-down assay. The interactions of UL36-UL37 and UL37-UL37 were verified with a coimmunoprecipitation assay. Knowledge of HSV-1 tegument protein-protein interactions will provide insights into the pathways of tegument assembly, and the identified interactions are potential targets for new antiviral drugs.
Regulation of Apobec3F and Human Immunodeficiency Virus Type 1 Vif by Vif-Cul5-ElonB/C E3 Ubiquitin Ligase
Authors: Liu Bindong , Sarkis Phuong Thi Nguyen , Luo Kun , Yu Yunkai , Yu Xiao-Fang 
Published: July 2005

ABSTRACT
The human cytidine deaminase Apobec3F (h-A3F), a protein related to the previously recognized antiviral factor Apobec3G (h-A3G), has antiviral activity against human immunodeficiency virus type 1 (HIV-1) that is suppressed by the viral protein Vif. The mechanism of HIV-1 Vif-mediated suppression of h-A3F is not fully understood. Here, we demonstrate that while h-A3F, like h-A3G, was able to suppress primate lentiviruses other than HIV-1 (simian immunodeficiency virus from African green monkeys [SIVagm] and Rhesus macaques [SIVmac]), the interaction between Vif proteins and h-A3F appeared to differ from that with h-A3G. H-A3F showed no change in its species specificity against HIV-1 or SIVagm Vif when a negatively charged amino acid was replaced with a lysine at position 128, a residue critical for h-A3G recognition by HIV-1 Vif. However, HIV-1 Vif, but not SIVagm Vif, was able to bind h-A3F and induce its polyubiquitination and degradation through the Cul5-containing E3 ubiquitin ligase. Interference with Cul5-E3 ligase function by depletion of Cul5, through RNA interference or overexpression of Cul5 mutants, blocked the ability of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that failed to recruit Cul5-E3 ligase but was still able to interact with h-A3F failed to suppress h-A3F. Interestingly, interference with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also increased the stability of HIV-1 Vif, suggesting that like the substrate molecules h-A3F and h-A3G, the substrate receptor protein Vif is itself also regulated by Cul5-E3 ligase. Our results indicate that Cul5-E3 ligase appears to be a common pathway hijacked by HIV-1 Vif to defeat both h-A3F and h-A3G. Developing inhibitors to disrupt the interaction between Vif and Cul5-E3 ligase could be therapeutically useful, allowing multiple host antiviral factors to suppress HIV-1.
mRNA Decay during Herpes Simplex Virus (HSV) Infections: Protein-Protein Interactions Involving the HSV Virion Host Shutoff Protein and Translation Factors eIF4H and eIF4A
Authors: Feng Pinghui , Everly David N. , Read G. Sullivan 
Published: July 2005

ABSTRACTDuring lytic infections, the virion host shutoff (Vhs) protein of herpes simplex virus accelerates the degradation of both host and viral mRNAs. In so doing, it helps redirect the cell from host to viral protein synthesis and facilitates the sequential expression of different viral genes. Vhs interacts with the cellular translation initiation factor eIF4H, and several point mutations that abolish its mRNA degradative activity also abrogate its ability to bind eIF4H. In addition, a complex containing bacterially expressed Vhs and a glutathioneS-transferase (GST)-eIF4H fusion protein has RNase activity. eIF4H shares a region of sequence homology with eIF4B, and it appears to be functionally similar in that both stimulate the RNA helicase activity of eIF4A, a component of the mRNA cap-binding complex eIF4F. We show that eIF4H interacts physically with eIF4A in the yeast two-hybrid system and in GST pull-down assays and that the two proteins can be coimmunoprecipitated from mammalian cells. Vhs also interacts with eIF4A in GST pull-down and coimmunoprecipitation assays. Site-directed mutagenesis of Vhs and eIF4H revealed residues of each that are important for their mutual interaction, but not for their interaction with eIF4A. Thus, Vhs, eIF4H, and eIF4A comprise a group of proteins, each of which is able to interact directly with the other two. Whether they interact simultaneously as a tripartite complex or sequentially is unclear. The data suggest a mechanism for linking the degradation of an mRNA to its translation and for targeting Vhs to mRNAs and to regions of translation initiation.
The Polerovirus Minor Capsid Protein Determines Vector Specificity and Intestinal Tropism in the Aphid
Authors: Brault Véronique , Périgon Sophie , Reinbold Catherine , Erdinger Monique , Scheidecker Danièle , Herrbach Etienne , Richards Ken , Ziegler-Graff Véronique 
Published: July 2005

ABSTRACTAphid transmission of poleroviruses is highly specific, but the viral determinants governing this specificity are unknown. We used a gene exchange strategy between two poleroviruses with different vectors,Beet western yellows virus(BWYV) andCucurbit aphid-borne yellows virus(CABYV), to analyze the role of the major and minor capsid proteins in vector specificity. Virus recombinants obtained by exchanging the sequence of the readthrough domain (RTD) between the two viruses replicated in plant protoplasts and in whole plants. The hybrid readthrough protein of chimeric viruses was incorporated into virions. Aphid transmission experiments using infected plants or purified virions revealed that vector specificity is driven by the nature of the RTD. BWYV and CABYV have specific intestinal sites in the vectors for endocytosis: the midgut for BWYV and both midgut and hindgut for CABYV. Localization of hybrid virions in aphids by transmission electron microscopy revealed that gut tropism is also determined by the viral origin of the RTD.
Regulation of Matrix Metalloproteinase 9 Expression by Epstein-Barr Virus Nuclear Antigen 3C and the Suppressor of Metastasis Nm23-H1
Authors: Kuppers Daniel A. , Lan Ke , Knight Jason S. , Robertson Erle S. 
Published: July 2005

ABSTRACT
Epstein-Barr virus latent protein EBNA3C has been shown to bind Nm23-H1, a known suppresser of cell migration and metastasis and a regulator of the guanine exchange factor Tiam-1. This interaction results in cellular translocation of Nm23-H1 to the nucleus and suppression of the antimigratory effect in vitro. Furthermore, these proteins can synergistically increase transcription of a basal promoter when targeted to DNA by fusion to a Gal4 DNA binding domain. In this report, we show that EBNA3C and Nm23-H1 can cooperate to upregulate expression of MMP-9, known to be expressed in aggressive forms of lymphomas. This upregulation resulted in increased levels of MMP-9 mRNA, as well as a detectable increase in MMP-9 gelatinolytic activity. Specific mutations in the MMP-9 promoter showed that the Ap1 and NFκB binding sites are important for upregulation by the proteins. Additionally, it was shown for the first time that EBNA3C and Nm23-H1 can bind subunits of these transcription factors. This suggests that the ability of EBNA3C to reverse the antimigratory effects of Nm23-H1 is likely to be in part through the synergistic upregulation of MMP-9, mediated through interactions with the AP1 and NFκB transcription factors.
Persistence of Bovine Viral Diarrhea Virus Is Determined by a Cellular Cofactor of a Viral Autoprotease
Authors: Lackner T. , Müller A. , König M. , Thiel H.-J. , Tautz N. 
Published: July 2005

ABSTRACTPolyprotein processing control is a crucial step in the life cycle of positive-strand RNA viruses. Recently, a vital autoprotease generating an essential viral replication factor was identified in such a virus, namely, the pestivirus bovine viral diarrhea virus. Surprisingly, the activity of this protease, which resides in nonstructural protein 2 (NS2), diminishes early after infection, resulting in the limitation of viral RNA replication. Here, we describe that a cellular chaperone termed Jiv (J-domain protein interacting with viral protein) acts as a cofactor of the NS2 protease. Consumption of the intracellular Jiv pool is responsible for temporal regulation of protease activity: overexpression of Jiv interfered with regulation and correlated with increased accumulation of viral RNA; downregulation of the cellular Jiv level accelerated the decline of protease activity and reduced intracellular viral RNA levels and virion production. Accordingly, the amount of a cellular protein controls pestiviral replication by limiting the generation of active viral protease molecules and replication complexes. Importantly, this unique mechanism of replication control is essential for maintenance of the noncytopathogenic phenotype of the virus and thereby for its ability to establish persistent infections. These results add an entirely novel aspect to the understanding of the molecular basis of viral persistence.