bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Import of Bovine Papillomavirus Type 1 E1 Protein Is Mediated by Multiple Alpha Importins and Is Negatively Regulated by Phosphorylation near a Nuclear Localization Signal
Authors: Bian Xue-Lin , Rosas-Acosta Germán , Wu Yu-Chieh , Wilson Van G. 
Published: December 2006

ABSTRACT
Papillomavirus DNA replication occurs in the nucleus of infected cells and requires the viral E1 protein, which enters the nuclei of host epithelial cells and carries out enzymatic functions required for the initiation of viral DNA replication. In this study, we investigated the pathway and regulation of the nuclear import of the E1 protein from bovine papillomavirus type 1 (BPV1). Using an in vitro binding assay, we determined that the E1 protein interacted with importins α3, α4, and α5 via its nuclear localization signal (NLS) sequence. In agreement with this result, purified E1 protein was effectively imported into the nucleus of digitonin-permeabilized HeLa cells after incubation with importin α3, α4, or α5 and other necessary import factors. We also observed that in vitro binding of E1 protein to all three α importins was significantly decreased by the introduction of pseudophosphorylation mutations in the NLS region. Consistent with the binding defect, pseudophosphorylated E1 protein failed to enter the nucleus of digitonin-permeabilized HeLa cells in vitro. Likewise, the pseudophosphorylation mutant showed aberrant intracellular localization in vivo and accumulated primarily on the nuclear envelope in transfected HeLa cells, while the corresponding alanine replacement mutant displayed the same cellular location pattern as wild-type E1 protein. Collectively, our data demonstrate that BPV1 E1 protein can be transported into the nucleus by more than one importin α and suggest that E1 phosphorylation by host cell kinases plays a regulatory role in modulating E1 nucleocytoplasmic localization. This phosphoregulation of nuclear E1 protein uptake may contribute to the coordination of viral replication with keratinocyte proliferation and differentiation.
The Antiviral Efficacy of Simian Immunodeficiency Virus-Specific CD8
+
T Cells Is Unrelated to Epitope Specificity and Is Abrogated by Viral Escape
Authors: Loffredo John T. , Burwitz Benjamin J. , Rakasz Eva G. , Spencer Sean P. , Stephany Jason J. , Giraldo Vela Juan Pablo , Martin Sarah R. , Reed Jason , Piaskowski Shari M. , Furlott Jessica , Weisgrau Kim L. , Rodrigues Denise S. , Soma Taeko , Napoé Gnankang , Friedrich Thomas C. , Wilson Nancy A. , Kallas Esper G. , Watkins David I. 
Published: December 2006

ABSTRACT

CD8
+
T lymphocytes appear to play a role in controlling human immunodeficiency virus (HIV) replication, yet routine immunological assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8
+
T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient. We used a functional in vitro assay to assess the abilities of different epitope-specific CD8
+
T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies of 26 epitope-specific CD8
+
T-cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01 or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificities of the CD8
+
T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat
28-35
SL8- and Gag
181-189
CM9-specific CD8
+
T-cell lines were consistently superior at suppressing viral replication compared to the other five SIV-specific CD8
+
T-cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat
28-35
SL8- and Gag
181-189
CM9-specific CD8
+
T-cell lines could suppress the replication of an escaped virus. Viral escape abrogated the abilities of Tat
28-35
SL8- and Gag
181-189
CM9-specific CD8
+
T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine.
Reduced Apoptosis in Human Intestinal Cells Cured of Persistent Poliovirus Infection
Authors: Labadie Karine , Saulnier Aure , Martin-Latil Sandra , Colbère-Garapin Florence 
Published: December 2006

ABSTRACT
Cells cured of persistent virus infection can be used to investigate cellular pathways of resistance to viral cytopathic effects. Persistent poliovirus (PV) infections were established in human intestinal Caco-2 cells, and spontaneously cured cell cultures were obtained. Two cell clones, cl6 and b13, cured of type 3 PV mutant infection and their parental Caco-2 cells were compared for susceptibility to PV infection, PV receptor CD155 expression, capacity to differentiate into polarized enterocytes, and PV-, staurosporine-, and actinomycin D-induced apoptosis. Our results strongly suggest that cells that are partially resistant to apoptosis can be selected during persistent virus infection.
Phylogenetic Analysis of Feline Immunodeficiency Virus in Feral and Companion Domestic Cats of New Zealand
Authors: Hayward Jessica J. , Taylor John , Rodrigo Allen G. 
Published: December 2006

ABSTRACTNested PCR was used to amplify envelope V3-V6 gene fragments of feline immunodeficiency virus (FIV) from New Zealand cats. Phylogenetic analyses established that subtypes A and C predominate among New Zealand cats, with clear evidence of intersubtype recombination. In addition, 17 sequences were identified that were distinct from all known FIV clades, and we tentatively suggest these belong to a novel subtype.
Complete Genome Analysis of 33 Ecologically and Biologically Diverse Rift Valley Fever Virus Strains Reveals Widespread Virus Movement and Low Genetic Diversity due to Recent Common Ancestry
Authors: Bird Brian H. , Khristova Marina L. , Rollin Pierre E. , Ksiazek Thomas G. , Nichol Stuart T. 
Published: December 2006

ABSTRACT

Rift Valley fever (RVF) virus is a mosquito-borne RNA virus responsible for large explosive outbreaks of acute febrile disease in humans and livestock in Africa with significant mortality and economic impact. The successful high-throughput generation of the complete genome sequence was achieved for 33 diverse RVF virus strains collected from throughout Africa and Saudi Arabia from 1944 to 2000, including strains differing in pathogenicity in disease models. While several distinct virus genetic lineages were determined, which approximately correlate with geographic origin, multiple exceptions indicative of long-distance virus movement have been found. Virus strains isolated within an epidemic (e.g., Mauritania, 1987, or Egypt, 1977 to 1978) exhibit little diversity, while those in enzootic settings (e.g., 1970s Zimbabwe) can be highly diverse. In addition, the large Saudi Arabian RVF outbreak in 2000 appears to have involved virus introduction from East Africa, based on the close ancestral relationship of a 1998 East African virus. Virus genetic diversity was low (∼5%) and primarily involved accumulation of mutations at an average of 2.9 × 10
−4
substitutions/site/year, although some evidence of RNA segment reassortment was found. Bayesian analysis of current RVF virus genetic diversity places the most recent common ancestor of these viruses in the late 1800s, the colonial period in Africa, a time of dramatic changes in agricultural practices and introduction of nonindigenous livestock breeds. In addition to insights into the evolution and ecology of RVF virus, these genomic data also provide a foundation for the design of molecular detection assays and prototype vaccines useful in combating this important disease.
Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis
Authors: Mottet-Osman Geneviève , Iseni Frédéric , Pelet Thierry , Wiznerowicz Maciej , Garcin Dominique , Roux Laurent 
Published: December 2006

ABSTRACT
Short RNA interference is more and more widely recognized as an effective method to specifically suppress viral functions in eukaryotic cells. Here, we used an experimental system that allows suppression of the Sendai virus (SeV) M protein by using a target sequence, derived from the green fluorescent protein gene, that was introduced in the 3′ untranslated region of the M protein mRNA. Silencing of the M protein gene was eventually achieved by a small interfering RNA (siRNA) directed against this target sequence. This siRNA was constitutively expressed in a cell line constructed by transduction with an appropriate lentivirus vector. Suppression of the M protein was sufficient to diminish virus production by 50- to 100-fold. This level of suppression had no apparent effect on viral replication and transcription, supporting the lack of M involvement in SeV transcription or replication control.
Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis
Authors: Samuel Melanie A. , Morrey John D. , Diamond Michael S. 
Published: December 2006

ABSTRACT

West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that has become a significant global cause of viral encephalitis. To examine the mechanisms of WNV-induced neuronal death and the importance of apoptosis in pathogenesis, we evaluated the role of a key apoptotic regulator, caspase 3. WNV infection induced caspase 3 activation and apoptosis in the brains of wild-type mice. Notably, congenic caspase 3
−/−
mice were more resistant to lethal WNV infection, although there were no significant differences in the tissue viral burdens or the kinetics of viral spread. Instead, decreased neuronal death was observed in the cerebral cortices, brain stems, and cerebella of caspase 3
−/−
mice. Analogously, primary central nervous system (CNS)-derived neurons demonstrated caspase 3 activation and apoptosis after WNV infection, and treatment with caspase inhibitors or a genetic deficiency in caspase 3 significantly decreased virus-induced death. These studies establish that caspase 3-dependent apoptosis contributes to the pathogenesis of lethal WNV encephalitis and suggest possible novel therapeutic targets to restrict CNS injury.
Evolution and Molecular Epidemiology of H9N2 Influenza A Viruses from Quail in Southern China, 2000 to 2005
Authors: Xu K. M. , Li K. S. , Smith G. J. D. , Li J. W. , Tai H. , Zhang J. X. , Webster R. G. , Peiris J. S. M. , Chen H. , Guan Y. 
Published: December 2006

ABSTRACT
H9N2 influenza viruses have become established and maintain long-term endemicity in terrestrial poultry in Asian countries. Occasionally these viruses transmit to other mammals, including humans. Increasing epidemiological and laboratory findings suggest that quail may be an important host, as they are susceptible to different subtypes of influenza viruses. To better understand the role of quail in influenza virus ecology and evolution, H9N2 viruses isolated from quail during 2000 to 2005 were antigenically and genetically characterized. Our results showed that H9N2 viruses are prevalent year-round in southern China and replicate mainly asymptomatically in the respiratory tract of quail. Genetic analysis revealed that both the G1-like and Ck/Bei-like H9N2 lineages were cocirculating in quail since 2000. Phylogenetic analyses demonstrated that most of the isolates tested were double- or multiple-reassortant variants, with four G1-like and 16 Ck/Bei-like genotypes recognized. A novel genotype of G1-like virus became predominant in quail since 2003, while multiple Ck/Bei-like genotypes were introduced into quail, wherein they incorporated G1-like gene segments, but none of them became established in this host. Those Ck/Bei-like reassortants generated in quail have then been introduced into other poultry. These complex interactions form a two-way transmission system between quail and other types of poultry. The present study provides evidence that H9N2 and H5N1 subtype viruses have also exchanged gene segments to generate currently circulating reassortants of both subtypes that have pandemic potential. Continuing influenza virus surveillance in poultry is critical to understanding the genesis and emergence of potentially pandemic strains in this region.
Aurintricarboxylic Acid Inhibits the Early Stage of Vaccinia Virus Replication byTargeting both Cellular and Viral Factors
Authors: Myskiw Chad , Deschambault Yvon , Jefferies Kristel , He Runtao , Cao Jingxin 
Published: December 2006

ABSTRACTAurintricarboxylic acid (ATA) has been shown to inhibit the replication of viruses from several different families, including human immunodeficiency virus, vesicular stomatitis virus, and the coronavirus causing severe acute respiratory syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is significantly abrogated upon ATA treatment, which is associated with the inhibition of early viral gene transcription. This inhibitory effect may be attributed to two findings. First, ATA blocks the phosphorylation of extracellular signal-regulated kinase 1/2, an event shown to be essential for vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA inhibits vaccinia virus replication by targeting both cellular and viral factors essential for the early stage of replication.
Sequence-Independent Targeting of Transmembrane Proteins Synthesized within Vaccinia Virus Factories to Nascent Viral Membranes
Authors: Husain Matloob , Weisberg Andrea S. , Moss Bernard 
Published: December 2006

ABSTRACT

The primary membrane of vaccinia virus, as well as those of other
poxviruses, forms within a discrete cytoplasmic factory region. We
recently determined the existence of an operative pathway from the
endoplasmic reticulum within the virus factory to nascent viral
membranes and demonstrated that a viral protein could be diverted from
this pathway to Golgi membranes by the addition of COPII-binding sites
(M. Husain, A. S. Weisberg, and B. Moss, Proc. Natl. Acad.
Sci. USA,
103:
19506-19511, 2006). Here we describe an
investigation of the structural features that are required for transit
of proteins to the viral membrane. Deletion of either the N-terminal
domain or the C-terminal cytoplasmic tail from the conserved A9 protein
did not prevent its incorporation into viral membranes, whereas
deletion of the transmembrane domain resulted in its distribution
throughout the cytoplasm. Nevertheless, replacement of the A9
transmembrane domain with the corresponding region of a nonpoxvirus
transmembrane protein or of a vaccinia virus extracellular envelope
protein allowed viral membrane targeting, indicating no requirement for
a specific amino acid sequence. Remarkably, the epitope-tagged A9
transmembrane domain alone, as well as a heterologous transmembrane
domain lacking a poxvirus sequence, was sufficient for viral membrane
association. The data are consistent with a sequence-independent
pathway in which transmembrane proteins that are synthesized within the
virus factory and lack COPII or other binding sites that enable
conventional endoplasmic reticulum exiting are incorporated into
nascent viral
membranes.
The Fitness Cost of Mutations Associated with Human Immunodeficiency Virus Type 1 Drug Resistance Is Modulated by Mutational Interactions
Authors: Cong Mian-er , Heneine Walid , García-Lerma J. Gerardo 
Published: December 2006

ABSTRACTIt is generally accepted that the fitness cost of resistance mutations plays a role in the persistence of transmitted drug-resistant human immunodeficiency virus type 1 and that mutations that confer a high fitness cost are less able to persist in the absence of drug pressure. Here, we show that the fitness cost of reverse transcriptase (RT) mutations can vary within a 72-fold range. We also demonstrate that the fitness cost of M184V and K70R can be decreased or enhanced by other resistance mutations such as D67N and K219Q. We conclude that the persistence of transmitted RT mutants might range widely on the basis of fitness and that the modulation of fitness cost by mutational interactions will be a critical determinant of persistence.
Prevalence and Abundance of Latently Transcribed Varicella-Zoster Virus Genes in Human Ganglia
Authors: Cohrs Randall J. , Gilden Donald H. 
Published: December 2006

ABSTRACT
In human ganglia latently infected with varicella-zoster virus (VZV), sequence analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66) are transcribed. However, their comparative prevalence and abundance are unknown. Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for RNA corresponding to the five virus genes known to be transcribed in latently infected human ganglia. The most prevalent transcript found was VZV gene 63 (78%), followed by gene 66 (43%), gene 62 (36%), and gene 29 (21%). No gene 21 transcripts were detected in any of the 28 ganglia. VZV gene 63 RNA was also the most abundant (3,710 ± 6,895 copies per 1 μg of mRNA) transcript detected in latently infected human ganglia, followed by VZV gene 29 (491 ± 594), VZV gene 66 (117 ± 85), and VZV gene 62 (64 ± 38). Thus, the repeated detection and high abundance of VZV gene 63 transcripts in latently infected ganglia suggests that VZV gene 63 may be more important for the maintenance of virus latency than the less abundantly transcribed and randomly detected VZV genes 21, 29, 62, and 66.
ALGORITHM FOR MULTIPLYING SCHUBERT CLASSES
Authors: DUAN HAIBAO , ZHAO XUEZHI 
Published: December 2006

Based on the formula for multiplying Schubert classes obtained in [17], we develop an algorithm computing the product of two arbitrary Schubert classes in a flag manifold G/H, where G is a compact connected Lie group and H ⊂ G is the centralizer of a one-parameter subgroup in G.Since all Schubert classes on G/H constitute a basis for the integral cohomology H*(G/H), the algorithm gives also a method to compute the integral cohomology ring H*(G/H) independent of the classical spectral sequence method of Leray and Borel [32, 33, 8, 9].
THE INDEX OF (WHITE) NOISES AND THEIR PRODUCT SYSTEMS
Authors: SKEIDE MICHAEL 
Published: December 2006

Almost every paper about Arveson systems (i.e. product systems of Hilbert spaces) starts by recalling their basic classification assigning to every Arveson system a type and an index. So it is natural to ask in how far an analogue classification can also be proposed for product systems of Hilbert modules. However, while the definition of type is plain, there are obstacles for the definition of index. But all obstacles can be removed when restricting to the category which we introduce here as spatial product systems and that matches the usual definition of spatial in the case of Arveson systems. This is not really a loss because the definition of index for nonspatial Arveson systems is rather formal and does not reflect the information the index carries for spatial Arveson systems.E0-semigroups give rise to product systems. Our definition of spatial product system, namely, existence of a unital unit that is central, matches Powers' definition of spatial in the sense that the E0-semigroup from which the product system is derived admits a semigroup of intertwining isometries. We show that every spatial product system contains a unique maximal completely spatial subsystem (generated by all units) that is isomorphic to a product system of time ordered Fock modules. (There exist nonspatial product systems that are generated by their units. Consequently, these cannot be Fock modules.) The index of a spatial product system we define as the (unique) Hilbert bimodule that determines the Fock module. In order to show that the index merits the name index we provide a product of product systems under which the index is additive (direct sum). While for Arveson systems there is the tensor product, for general product systems the tensor product does not make sense as a product system. Even for Arveson systems our product is, in general, only a subsystem of the tensor product. Moreover, its construction depends explicitly on the choice of the central reference units of its factors.Spatiality of a product system means that it may be derived from an E0-semigroup with an invariant vector expectation, i.e. from a noise. We extend our product of spatial product systems to a product of noises and study its properties.Finally, we apply our techniques to show the module analogue of Fowler's result that free flows are comletely spatial, and we compute their indices.
THE ANALYSIS OF BINDING PATTERNS ON DIFFERENT RECEPTORS BOUND TO HEMAGGLUTININ OF AVIAN AND AVIAN-LIKE INFLUENZA VIRUS USING QUANTUM CHEMICAL CALCULATIONS
Authors: SANGMA C. , NUNRIUM P. , HANNONGBUA S. 
Published: December 2006

While there has been no pandemic outbreak of influenza evolving from the H5N1 strain yet, the virus has already killed people. This suggests that without any significant mutations the influenza virus can live within the human body for days in which its life cycles can continue. The first step for infection is the host cell surface binding which is the function of the glycoprotein hemagglutinin (HA). In this investigation, quantum chemical calculations were performed on the systems comprising four structures coming from parts of the HA, with its cell receptor-analog substrate, determined from X-ray structures of the 1934 Spanish flu and avian influenza antigens. The calculations are aimed at partitioning the system into several parts, thus obtaining global and partial contributions of binding energy from each of them. As a result, it was possible to propose quantitatively the main contributions of key amino residues of the avian influenza virus glycoprotein around the binding pocket relevant to the binding process.The main binding energy contributions of the Spanish flu HA were from Tyr95, Val135, Thr136, Ala137, Glu190, Asp225, and Gln226, while the main contributions of the avian flu HA were from Ser129, Val131, Ser132, and Ser133. It was also found that the effect from the HA with an avian characteristic, Gln226 and Gly228, was not relatively high according to the contributed binding energy, whereas the effect from nearby water molecules was significant. Thus, it was concluded that both human and avian virus HA could recognize human cell receptors better than the avian cell receptors according to the binding energy. Therefore, the preference to any particular cell receptor types might involve some other factors rather than being determined solely by the HA binding process.