bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ty3 Nucleocapsid Controls Localization of Particle Assembly
Authors: Larsen Liza S. Z. , Beliakova-Bethell Nadejda , Bilanchone Virginia , Zhang Min , Lamsa Anne , DaSilva Rhonda , Hatfield G. Wesley , Nagashima Kunio , Sandmeyer Suzanne 
Published: December 2007

ABSTRACT

Expression of the budding yeast retrotransposon Ty3 results in production of viruslike particles (VLPs) and retrotransposition. The Ty3 major structural protein, Gag3, similar to retrovirus Gag, is processed into capsid, spacer, and nucleocapsid (NC) during VLP maturation. The 57-amino-acid Ty3 NC protein has 17 basic amino acids and contains one copy of the CX
2
CX
4
HX
4
C zinc-binding motif found in retrovirus NC proteins. Ty3 RNA, protein, and VLPs accumulate in clusters associated with RNA processing bodies (P bodies). This study investigated the role of the NC domain in Ty3-P body clustering and VLP assembly. Fifteen Ty3 NC Ala substitution and deletion mutants were examined using transposition, immunoblot, RNA protection, cDNA synthesis, and multimerization assays. Localization of Ty3 proteins and VLPs was characterized microscopically. Substitutions of each of the conserved residues of the zinc-binding motif resulted in the loss of Ty3 RNA packaging. Substitution of the first two of four conserved residues in this motif caused the loss of Ty3 RNA and protein clustering with P bodies and disrupted particle formation. NC was shown to be a mediator of formation of Ty3 RNA foci and association of Ty3 RNA and protein with P bodies. Mutations that disrupted these NC functions resulted in various degrees of Gag3 nuclear localization and a spectrum of different particle states. Our findings are consistent with the model that Ty3 assembly is associated with P-body components. We hypothesize that the NC domain acts as a molecular switch to control Gag3 conformational states that affect both assembly and localization.
Fusogenicity of Jaagsiekte Sheep Retrovirus Envelope Protein Is Dependent on Low pH and Is Enhanced by Cytoplasmic Tail Truncations
Authors: Côté Marceline , Zheng Yi-Min , Albritton Lorraine M. , Liu Shan-Lu 
Published: December 2007

ABSTRACT

Jaagsiekte sheep retrovirus (JSRV) envelope (
Env
) is an active oncogene responsible for neoplastic transformation in animals and cultured cells. In this study, we used syncytium induction and fluorescence-based cell fusion assays to investigate JSRV Env fusion and its modulation by the cytoplasmic tail (CT). We found that JSRV Env induced syncytia in cells overexpressing the receptor for JSRV and that a low pH was required for this process to occur. Fusion kinetics studies revealed that cell-cell fusion by JSRV Env at neutral pH was poor, taking up to a day, in sharp contrast to fusion at low pH, which peaked within 2 min following a low-pH trigger. Deletion of the C-terminal 7 or 16 amino acids of the JSRV Env CT had no or little effect on fusion, yet additional truncation toward the membrane-spanning domain, resulting in mutants retaining as little as 1 amino acid of the CT, led to progressively increased syncytium formation at neutral pH that was further enhanced by low-pH treatment. Notably, the severely truncated mutants showed elevated levels of surface subunits in culture medium, suggesting that the CT truncations resulted in conformational changes in the ectodomain of Env that impaired surface subunit associations. Taken together, this study reveals for the first time that the fusion activity of the JSRV Env protein is dependent on a low pH and is modulated by the CT, whose truncation overcomes, at least partially, the low-pH requirement for fusion and enhances Env fusion activity and kinetics.
Tobacco Mosaic VirusReplicase-Auxin/Indole Acetic Acid Protein Interactions: Reprogramming the Auxin Response Pathway To Enhance Virus Infection
Authors: Padmanabhan Meenu S. , Kramer Sabrina R. , Wang Xiao , Culver James N. 
Published: December 2007

ABSTRACTThe replicase protein ofTobacco mosaic virus(TMV) disrupts the localization and stability of interacting auxin/indole acetic acid (Aux/IAA) proteins inArabidopsis, altering auxin-mediated gene regulation and promoting disease development (M. S. Padmanabhan, S. P. Goregaoker, S. Golem, H. Shiferaw, and J. N. Culver, J. Virol. 79:2549-2558, 2005). In this study, a similar replicase-Aux/IAA interaction affecting disease development was identified in tomato. The ability of the TMV replicase to interact with Aux/IAA proteins from diverse hosts suggests that these interactions contribute to the infection process. To examine the role of this interaction in virus pathogenicity, the replication and spread of a TMV mutant with a reduced ability to interact with specific Aux/IAA proteins were examined. Within young (4- to 6-week-old) leaf tissue, there were no significant differences in the abilities of Aux/IAA-interacting or -noninteracting viruses to replicate and spread. In contrast, in mature (10- to 12-week-old) leaf tissue, the inability to interact with specific Aux/IAA proteins correlated with a significant reduction in virus accumulation. Correspondingly, interacting Aux/IAA levels are significantly higher in older tissue and the overaccumulation of a degradation-resistant Aux/IAA protein reduced virus accumulation in young leaf tissue. Combined, these findings suggest that TMV replicase-Aux/IAA interactions selectively enhance virus pathogenicity in tissues where Aux/IAA proteins accumulate. We speculate that the virus disrupts Aux/IAA functions as a means to reprogram the cellular environment of older cells to one that is more compatible for virus replication and spread.
Pseudodiploid Genome Organization Aids Full-Length Human Immunodeficiency Virus Type 1 DNA Synthesis
Authors: King Steven R. , Duggal Nisha K. , Ndongmo Clement B. , Pacut Crystal , Telesnitsky Alice 
Published: December 2007

ABSTRACT

Template switching between copackaged human immunodeficiency virus type 1 (HIV-1) genomic RNAs is genetically silent when identical RNAs are copackaged but yields recombinants when virions contain two distinct RNAs. Sequencing has revealed that errors at retroviral recombination junctions are infrequent, suggesting that template switching is not intrinsically mutagenic. Here, we tested the hypothesis that template switching may instead contribute to replication fidelity. This hypothesis predicts that reverse transcription of a single-copy gene will be more error prone than replication in the presence of a second copy. To test this, HIV-1-based vectors containing both
lacZ
and the puromycin resistance marker were expressed either alone or with an excess of an “empty” vector lacking
lacZ
and
puro
. This resulted in virions with either RNA homodimers or haploid genomes with only a single
lacZ-puro
RNA. In untreated cells,
lacZ
inactivation rates suggested that haploid vector reverse transcription was slightly more error prone than that of homodimerized pseudodiploid vectors. Haploid reverse transcription was at least threefold more error prone than pseudodiploid-templated synthesis when slowed by hydroxyurea treatment or stopped prematurely with zidovudine. Individual products of one- and two-copy genes revealed both nucleotide substitutions and deletions, with deletions more frequent than point mutations among haploid genome products. Similar spectra of defective products were observed at early reverse transcription time points and among products of haploid virions. These results indicate that faithful, full-length reverse transcription products were underrepresented in the absence of a reserve of genetic information and suggest that template switching contributes to HIV-1 genomic integrity.
Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug Design
Authors: Xue Xiaoyu , Yu Hongwei , Yang Haitao , Xue Fei , Wu Zhixin , Shen Wei , Li Jun , Zhou Zhe , Ding Yi , Zhao Qi , Zhang Xuejun C. , Liao Ming , Bartlam Mark , Rao Zihe 
Published: December 2007

ABSTRACT

Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M
pro
), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) M
pro
and a severe acute respiratory syndrome CoV (SARS-CoV) M
pro
mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M
pro
. A monomeric form of IBV M
pro
was identified for the first time in CoV M
pro
structures. A comparison of these two structures to other available M
pro
structures provides new insights for the design of substrate-based inhibitors targeting CoV M
pro
s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M
pro
and was found to demonstrate in vitro inactivation of IBV M
pro
and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M
pro
.
Transdominant Inhibition of Bovine Viral Diarrhea Virus Entry
Authors: Tscherne Donna M. , Evans Matthew J. , MacDonald Margaret R. , Rice Charles M. 
Published: December 2007

ABSTRACT

Bovine viral diarrhea virus
(BVDV) is a positive-strand RNA virus and a member of the genus
Pestivirus
in the family
Flaviviridae
. To identify and characterize essential factors required for BVDV replication, a library expressing random fragments of the BVDV genome was screened for sequences that act as transdominant inhibitors of viral replication by conferring resistance to cytopathic BVDV-induced cell death. We isolated a BVDV-nonpermissive MDBK cell clone that harbored a 1.2-kb insertion spanning the carboxy terminus of the envelope glycoprotein 1 (E1), the envelope glycoprotein E2, and the amino terminus of p7. Confirming the resistance phenotype conferred by this library clone, naïve MDBK cells expressing this fragment were found to be 100- to 1,000-fold less permissive to both cytopathic and noncytopathic BVDV infection compared to parental MDBK cells, although these cells remained fully permissive to vesicular stomatitis virus. This restriction could be overcome by electroporation of BVDV RNA, indicating a block at one or more steps in viral entry prior to translation of the viral RNA. We determined that the E2 ectodomain was responsible for the inhibition to BVDV entry and that this block occurred downstream from BVDV interaction with the cellular receptor CD46 and virus binding, suggesting interference with a yet-unidentified BVDV entry factor.
A Single-Amino-Acid Substitution in the Tvb
S1
Receptor Results in Decreased Susceptibility to Infection by Avian Sarcoma and Leukosis Virus Subgroups B and D and Resistance to Infection by Subgroup E In Vitro and In Vivo
Authors: Reinišová Markéta , Šenigl Filip , Yin Xueqian , Plachý Jiří , Geryk Josef , Elleder Daniel , Svoboda Jan , Federspiel Mark J. , Hejnar Jiří 
Published: December 2007

ABSTRACT

The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of ASLV. The
tvb
gene encodes the receptor for subgroups B, D, and E ASLVs. The wild-type Tvb
S1
receptor confers susceptibility to subgroups B, D, and E ASLVs. In this study, the genetic defect that accounts for the altered susceptibility of an inbred chicken line, line M, to infection by ASLV(B), ASLV(D), and ASLV(E) was identified. The
tvb
gene in line M,
tvb

r2

, encodes a mutant Tvb
S1
receptor protein with a substitution of a serine for a cysteine at position 125 (C125S). Here, we show that the C125S substitution in Tvb
S1
significantly reduces the susceptibility of line M cells to infection by ASLV(B) and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in cultured cells and in the incidence and growth of avian sarcoma virus-induced sarcomas in chickens. The C125S substitution significantly reduces the binding affinity of the Tvb
S1
receptor for the subgroup B, D, and E ASLV envelope glycoproteins. These are the first results that demonstrate a possible role of the cysteine-rich domain 3 in the function of the Tvb receptors.
Molecular Characterization of Feline Immunodeficiency Virus Budding
Authors: Luttge Benjamin G. , Shehu-Xhilaga Miranda , Demirov Dimiter G. , Adamson Catherine S. , Soheilian Ferri , Nagashima Kunio , Stephen Andrew G. , Fisher Robert J. , Freed Eric O. 
Published: December 2007

ABSTRACT
Infection of domestic cats with feline immunodeficiency virus (FIV) is an important model system for studying human immunodeficiency virus type 1 (HIV-1) infection due to numerous similarities in pathogenesis induced by these two lentiviruses. However, many molecular aspects of FIV replication remain poorly understood. It is well established that retroviruses use short peptide motifs in Gag, known as late domains, to usurp cellular endosomal sorting machinery and promote virus release from infected cells. For example, the Pro-Thr/Ser-Ala-Pro [P(T/S)AP] motif of HIV-1 Gag interacts directly with Tsg101, a component of the endosomal sorting complex required for transport I (ESCRT-I). A Tyr-Pro-Asp-Leu (YPDL) motif in equine infectious anemia virus (EIAV), and a related sequence in HIV-1, bind the endosomal sorting factor Alix. In this study we sought to identify and characterize FIV late domain(s) and elucidate cellular machinery involved in FIV release. We determined that mutagenesis of a PSAP motif in FIV Gag, small interfering RNA-mediated knockdown of Tsg101 expression, and overexpression of a P(T/S)AP-binding fragment of Tsg101 (TSG-5′) each inhibited FIV release. We also observed direct binding of FIV Gag peptides to Tsg101. In contrast, mutagenesis of a potential Alix-binding motif in FIV Gag did not affect FIV release. Similarly, expression of the HIV-1/EIAV Gag-binding domain of Alix (Alix-V) did not disrupt FIV budding, and FIV Gag peptides showed no affinity for Alix-V. Our data demonstrate that FIV relies predominantly on a Tsg101-binding PSAP motif in the C terminus of Gag to promote virus release in HeLa cells, and this budding mechanism is highly conserved in feline cells.
Facts and theories on the Andes
Authors: GANSSER AUGUSTO 
Published: December 2007

Theories on the relation of oceanic plates with continents frequently use the Andes as a model. Simplified assumptions neglect the fact that only the recent morphogenic uplift made the apparently uniform Andes, masking a most complicated geological history.
Three main subdivisions are recognized. (I) The Southern Andes that show a virgation leading into the Scotia arc. Oceanic formations characterize the interior ranges and disappear towards the Gulf of Penas, where the Chile fracture zone joins the continent. (2) From here the Central Andes begin with a Coastal Cordillera of metamorphic, highly compressed Paleozoic and probably older rocks with an abnormal northwest strike. They are transgressed by thick, mostly volcanic Mesozoic rocks, with block fold tectonics. An intense young acid volcanism characterizes the Central ranges together with strong seismic activity that is missing in the Southern Andes. The Central Andes are bordered by the Nasca plate, which is subdivided by the aseismic Nasca ridge. The latter projects into the Andes where the metamorphic Coastal belt disappears.
(3) The Northern Andes have a marked virgation leading into the Caribbean are and display a Coastal and Western (Caribbean) Cordillera of more or less metamorphic Mesozoic oceanic rocks, in strong contrast to the Central Andes. Their southern border coincides with a major east-west lineament. This is outlined by the Carnegie–Galapagos ridge and a possible renewal of an old Amazon fracture trend aligned with the Romanche fracture zone which displaces the Mid-Atlantic ridge. The continental edge of the Cocos plate, bordering the Northern Andes, exposes oceanic sediments in marked contrast to the coastal metamorphic “basement” of the Central Andes, that borders the Nasca plate.
The Andes, being a marginal chain, are influenced by the shields to the east, which display younger remobilization along fracture zones, and by the east Pacific plates in the west. The geological complexities of the Andes, with their marked volcanism and irregular but strong seismicity, suggest that the east Pacific plates have had a much more complicated pattern than has generally been supposed.
The overturned anticline of the Northern Range of Trinidad near Port of Spain
Authors: POTTER HENRY C. 
Published: December 2007

Formerly
the Northern Range of Trinidad was assumed to be the south flank of an anticline, with the north flank either out to sea or displaced by faulting. Mapping has shown that the structure is that of an anticline overturned to the north.

The steep southern limb begins with nearly vertical dips in the Chancellor formation and the Morvant beds along the Lady Young Road, and between Port of Spain and Maraval. In this upright limb are local folds 100 m to 500 m in wavelength, parallel with both the main structure and minor folds. Folds of this size have not been recognised in the overturned northern limb. West of Maraval step-like folds with alternating horizontal and vertical limbs occur on east–west axes 10 m to 100 m apart. Axial surfaces dip about 35°N, but all other minor folds in the area have axial surfaces dipping steeply southwards.
Along the axis of the main fold, which occurs in the outcrop of the Maraval limestones, dips are 40°–60°S and the flanks are isoclinal. In the whole of the over-turned northern limb dips are much flatter, commonly less than 25°, and appear to become even flatter to the north. The size of this recumbent limb suggests that it is a nappe. The underlying autochthonous beds are not seen.
A number of phases of folding are recognisable. The first folds on east-west axes were refolded on more or less parallel axes. The step-like folding west of Maraval may belong to this
A lead isotope study of Archaean mineralized areas in Tanzania
Authors: COOMER PETER G. , ROBERTSON DAVID K. 
Published: December 2007

Single-stage lead extracted from pyrite and galena collected from Nyanzian greenstone belts in the northern half of the Tanzanian Shield yields a recalculated model age of 2700 ± 150 m.y. for the gold mineralization, a date that is consistent with existing radiometric ages. Anomalous multi-stage lead has also been found in the Nyanzian sulphides, and is interpreted as indicating that radiogenic lead was added to the original lead during an event 900 ± 300 m.y. ago. This event is tentatively correlated with the Bukoban phase of basic dyke intrusion.
Two mineralized areas in the adjacent Ubendian Orogenic Belt were also investigated. Lead from the Mpanda Mineral Field, also apparently single-stage, yields a model age of 1400 ±150 m.y. for the mineralization. Anomalous multi-stage leads from the Lupa Goldfield indicate that the area has experienced a complex history starting with a mineralizing event at least 2400 ±150 m.y. ago.
Facies relations in the Eocene-Oligocene in the Santa Ynez Mountains, California
Authors: VAN DE KAMP P. C. , HARPER J. D. , GONNIFF J. J. , MORRIS D. A. 
Published: December 2007

Facies relationships between deep and shallow marine to continental deposits in the Eocene-Oligocene sequence of the Santa Ynez Mountains, California, have been studied in detail to (i) determine interrelationships between shallower and deeper marine sands (coastal and turbidite); (2) establish criteria for the recognition of genetic sand types; (3) determine factors influencing facies distribution; and (4) propose hypotheses of marine sand deposition. The rocks studied include the Anita, Sierra Blanca, Juncal (with the Camino Cielo Member), Matilija, Cozy Dell, and “Coldwater” formations but not the topmost unit of the Eocene-Oligocene sequence, the non-marine Sespe formation.
In landward sequence, the facies recognized include: Turbidites and marine lutites, proximal turbidites, shallow marine, coastal and continental facies. These occur in two major regressive sequences. In the first, the Juncal-Matilija sequence, thin-bedded turbidites and marine lutites are overlain by, and are laterally equivalent to, very thick proximal turbidites which pass upward into shallow marine and coastal sands. The major sand accumulations are in the basin margin shallow marine, coastal, and proximal turbidite facies. The second regression, the Cozy Dell-Sespe sequence, lacks significant proximal turbidite deposits but has extensive shallow marine and coastal deposits. Facies distribution and stratigraphical sequence are explained as responses to the interplay of depositional and structural processes.
Detailed stratigraphical mapping has clarified correlation in the Eocene sequence to the Santa Ynez Mountains. Micropaleontology is used in support of correlations and bathy-metric interpretations.
Cyprus umbers: basalt-sediment relationships on a Mesozoic ocean ridge
Authors: ROBERTSON A. H. F. 
Published: December 2007

Overlying the upper pillow Lavas, the latest extrusives of the Troodos Massif, interpreted as Cretaceous ocean floor, there occur umbers; iron, manganese and trace-metal enriched mudstones of volcanic exhalative origin.Umber deposits occur in hollows, underline by thin lava breccias, also by deeper zones of intensely veined and fragmented pillow lavas. Occasional thicker umber deposits are located in elongate fault-controlled depressions; within and above thick lava breccias, restricted to the south margin of the Troodos Massif; and also in depressoions inherited from earlier emplacement of stratiform cupriferous sulphides.Umbers originated in the Campanian due to volcanism on an ocean ridge. The sub-umber veining and brecciation was produced by late-stage hydrothermal activity, associated initially, with a brief episode of violent volcanism, then with more quiescent discharge of submarine thermal springs from a geothermal system. Large volumes if dilute metalliferous brines were released into open marine waters whereupon umbers were rapidly precipitated.