bluuebunny/crossref_metadata_2025_split huggingface dataset:
Islam and Democracy: Is Modernization a Barrier?
Authors: Voll John O. 
Published: November 2006

AbstractThe relationship between Islam and democracy is a hotly debated topic. Usually the disagreements are expressed in a standard form. In this form, the debaters’ definitions of “Islam” and “democracy” determine the conclusions arrived at. It is possible, depending upon the definitions used, to “prove” both positions: Islam and democracy are compatible and that they are not. To escape from the predefined conclusions, it is necessary to recognize that “Islam” and “democracy” are concepts with many definitions. In the twenty‐first century, important interpretations of Islam open the way for political visions in which Islam and democracy are mutually supportive.
Respiratory Syncytial Virus F Envelope Protein Associates with Lipid Rafts without a Requirement for Other Virus Proteins
Authors: Fleming Elisa H. , Kolokoltsov Andrey A. , Davey Robert A. , Nichols Joan E. , Roberts Norbert J. 
Published: November 2006

ABSTRACT
Like many enveloped viruses, human respiratory syncytial virus (RSV) assembles at and buds from lipid rafts. Translocation of the envelope proteins to these membrane subdomains is essential for production of infectious virus, but the targeting mechanism is poorly understood and it is not known if other virus proteins are required. Here we demonstrate that F protein of RSV intrinsically targets to lipid rafts without a requirement for any other virus protein, including the SH and G envelope proteins. Recombinant virus deficient in SH and G but retaining F protein expression was used to demonstrate that F protein still localized in rafts in both A549 and HEp-2 cells. Expression of a recombinant F gene by use of plasmid vectors demonstrated that F contains its own targeting domain and localized to rafts in the absence of other virus proteins. The domain responsible for translocation was then mapped. Unlike most other virus envelope proteins, F is unusual since the target signal is not contained within the cytoplasmic domain nor did it involve fatty acid modified residues. Furthermore, exchange of the transmembrane domain with that of the vesicular stomatitis virus G protein, a nonraft protein, did not alter F protein raft localization. Taken together, these data suggest that domains present in the extracellular portion of the protein are responsible for lipid raft targeting of the RSV F protein.
Evidence of Influenza A Virus RNA in Siberian Lake Ice
Authors: Zhang Gang , Shoham Dany , Gilichinsky David , Davydov Sergei , Castello John D. , Rogers Scott O. 
Published: November 2006

ABSTRACT
Influenza A virus infects a large proportion of the human population annually, sometimes leading to the deaths of millions. The biotic cycles of infection are well characterized in the literature, including in studies of populations of humans, poultry, swine, and migratory waterfowl. However, there are few studies of abiotic reservoirs for this virus. Here, we report the preservation of influenza A virus genes in ice and water from high-latitude lakes that are visited by large numbers of migratory birds. The lakes are along the migratory flight paths of birds flying into Asia, North America, Europe, and Africa. The data suggest that influenza A virus, deposited as the birds begin their autumn migration, can be preserved in lake ice. As birds return in the spring, the ice melts, releasing the viruses. Therefore, temporal gene flow is facilitated between the viruses shed during the previous year and the viruses newly acquired by birds during winter months spent in the south. Above the Arctic Circle, the cycles of entrapment in the ice and release by melting can be variable in length, because some ice persists for several years, decades, or longer. This type of temporal gene flow might be a feature common to viruses that can survive entrapment in environmental ice and snow.
Strain Fidelity of Chronic Wasting Disease upon Murine Adaptation
Authors: Sigurdson Christina J. , Manco Giuseppe , Schwarz Petra , Liberski Pawel , Hoover Edward A. , Hornemann Simone , Polymenidou Magdalini , Miller Michael W. , Glatzel Markus , Aguzzi Adriano 
Published: November 2006

ABSTRACT

Chronic wasting disease (CWD), a prion disease of deer and elk, is highly prevalent in some regions of North America. The establishment of mouse-adapted CWD prions has proven difficult due to the strong species barrier between mice and deer. Here we report the efficient transmission of CWD to transgenic mice overexpressing murine PrP. All mice developed disease 500 ± 62 days after intracerebral CWD challenge. The incubation period decreased to 228 ± 103 days on secondary passage and to 162 ± 6 days on tertiary passage. Mice developed very large, radially structured cerebral amyloid plaques similar to those of CWD-infected deer and elk. PrP
Sc
was detected in spleen, indicating that murine CWD was lymphotropic. PrP
Sc
glycoform profiles maintained a predominantly diglycosylated PrP pattern, as seen with CWD in deer and elk, across all passages. Therefore, all pathological, biochemical, and histological strain characteristics of CWD appear to persist upon repetitive serial passage through mice. These findings indicate that the salient strain-specific properties of CWD are encoded by agent-intrinsic components rather than by host factors.
Analyses of the Interaction between the Origin Binding Domain from Simian Virus 40 T Antigen and Single-Stranded DNA Provide Insights into DNAUnwinding and Initiation of DNA Replication
Authors: Reese Danielle K. , Meinke Gretchen , Kumar Anuradha , Moine Stephanie , Chen Kathleen , Sudmeier James L. , Bachovchin William , Bohm Andrew , Bullock Peter A. 
Published: November 2006

ABSTRACT
DNA
helicases are essential for DNA metabolism; however, at the molecular
level little is known about how they assemble or function. Therefore,
as a model for a eukaryotic helicase, we are analyzing T antigen (T-ag)
the helicase encoded by simian virus 40. In this study, nuclear
magnetic resonance (NMR) methods were used to investigate the transit
of single-stranded DNA (ssDNA) through the T-ag origin-binding domain
(T-ag OBD). When the residues that interact with ssDNA are viewed in
terms of the structure of a hexamer of the T-ag OBD, comprised of
residues 131 to 260, they indicate that ssDNA passes over one face of
the T-ag OBD and then transits through a gap in the open ring
structure. The NMR-based conclusions are supported by an analysis of
previously described mutations that disrupt critical steps during the
initiation of DNA replication. These and related observations are
discussed in terms of the threading of DNA through T-ag hexamers and
the initiation of viral DNA
replication.
Characterization of an Immunodominant Antigenic Site on GB Virus C Glycoprotein E2 That Is Involved in Cell Binding
Authors: McLinden James H. , Kaufman Thomas M. , Xiang Jinhua , Chang Qing , Klinzman Donna , Engel Alfred M. , Hess Georg , Schmidt Urban , Houghton Michael , Stapleton Jack T. 
Published: November 2006

ABSTRACT
GB virus type C (GBV-C) is a human flavivirus that may cause persistent infection, although most infected individuals clear viremia and develop antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to topologically map immunogenic sites on GBV-C E2 and for the ability to detect or block recombinant E2 binding to various cell lines. Five competition groups of MAbs were identified. Groups I and II did not compete with each other. Group III competed with both groups I and II. Group IV did not compete with group I, II, or III. One MAb competed with all of the other MAbs, suggesting that the epitopes bound by these MAbs are intimately related. Individually, none of the MAbs competed extensively with polyclonal human convalescent antibody (PcAb); however, combinations of all five MAb groups completely blocked PcAb binding to E2, suggesting that the epitopes bound by these MAbs form a single, immunodominant antigenic site. Only group I and III MAbs detected purified recombinant E2 bound to cells in binding assays. In contrast, group II MAbs neutralized the binding of E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the peptide included four C-terminal or eight N-terminal residues, suggesting that the GBV-C E2 protein contains a single immunodominant antigenic site which includes a complex epitope that is involved in specific cellular binding.
Reovirus μ1 Structural Rearrangements That Mediate Membrane Penetration
Authors: Zhang Lan , Chandran Kartik , Nibert Max L. , Harrison Stephen C. 
Published: November 2006

ABSTRACT
Membrane penetration by nonenveloped reoviruses is mediated by the outer-capsid protein, μ1 (76 kDa). Previous evidence has suggested that an autolytic cleavage in μ1 allows the release of its N-terminally myristoylated peptide, μ1N (4 kDa), which probably then interacts with the target-cell membrane. A substantial rearrangement of the remaining portion of μ1, μ1C (72 kDa), must also have occurred for μ1N to be released, and some regions in μ1C may make additional contacts with the membrane. We describe here a particle-free system to study conformational rearrangements of μ1. We show that removal of the protector protein σ3 is not sufficient to trigger rearrangement of free μ1 trimer and that free μ1 trimer undergoes conformational changes similar to those of particle-associated μ1 when induced by similar conditions. The μ1 rearrangements require separation of the μ1 trimer head domains but not the μ1N/C autocleavage. We have also obtained a relatively homogeneous form of the structurally rearranged μ1 (μ1*) in solution. It is an elongated monomer and retains substantial α-helix content. We have identified a protease-resistant ∼23-kDa fragment of μ1*, which contains the largely α-helical regions designated domains I and II in the conformation of μ1 prior to rearrangement. We propose that the μ1 conformational changes preceding membrane penetration or disruption during cell entry involve (i) separation of the β-barrel head domains in the μ1 trimer, (ii) autolytic cleavage at the μ1N/C junction, associated with partial unfolding of μ1C and release of μ1N, and (iii) refolding of the N-terminal helical domains of μ1C, with which μ1N was previously complexed, accompanied by dissociation of the μ1 trimer.
Mutational Analysis of the Lassa Virus Promoter
Authors: Hass Meike , Westerkofsky Martina , Müller Stefanie , Becker-Ziaja Beate , Busch Carola , Günther Stephan 
Published: November 2006

ABSTRACT
The
promoter sequences directing viral gene expression and genome
replication of arenaviruses reside within the 3′ and 5′
termini of each RNA segment. The terminal 19 nucleotides at both ends
are highly conserved among all arenavirus species and are almost
completely complementary to each other. This study aimed at
characterizing the Lassa virus promoter in detail. The relevance of
each position in the promoter was studied by site-directed mutagenesis
using the Lassa virus minireplicon system. The data indicate that the
Lassa virus promoter functions as a duplex, regulates transcription and
replication in a coordinated manner, and is composed of two functional
elements, a sequence-specific region from residue 1 to 12 and a
variable complementary region from residue 13 to 19. The first region
appears to interact with the replication complex mainly via
base-specific interactions, while in the second region solely base
pairing between 3′ and 5′ promoter ends is important
for promoter
function.
NFAT4 Is Required for JC Virus Infection of Glial Cells
Authors: Manley Kate , O'Hara Bethany A. , Gee Gretchen V. , Simkevich Carl P. , Sedivy John M. , Atwood Walter J. 
Published: November 2006

ABSTRACT
The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In immunosuppressed patients, JCV infection can lead to progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). The majority of PML cases occur in the setting of human immunodeficiency virus (HIV) infection, and it has been suggested that the link between HIV and the development of PML is in part related to the production of numerous cytokines in the CNS during HIV infection. To examine the link between the expression of inflammatory cytokines and JCV infection, we tested an anti-inflammatory compound, cyclosporine A (CsA), for its ability to block JCV infection of glial cells. We found that CsA inhibited JCV infection by preventing the activation of the transcription factor nuclear factor of activated T cells 4 (NFAT4). Luciferase reporter assays and chromatin immunoprecipitation assays revealed that NFAT4 directly bound the JCV promoter during infection and was important for the activation of both early and late transcription. In addition, the expression of the JCV early viral gene products increased NFAT activity to further aid viral transcription. The necessity of NFAT for JCV infection suggests that calcium signaling and the activation of NFAT in glial cells are required for JCV infection of the CNS.
Access to Nectin Favors Herpes Simplex Virus Infection at the Apical Surface of Polarized Human Epithelial Cells
Authors: Galen Benjamin , Cheshenko Natalia , Tuyama Ana , Ramratnam Bharat , Herold Betsy C. 
Published: November 2006

ABSTRACT
Viral entry may preferentially occur at the apical or the basolateral surfaces of polarized cells, and differences may impact pathogenesis, preventative strategies, and successful implementation of viral vectors for gene therapy. The objective of these studies was to examine the polarity of herpes simplex virus (HSV) entry using several different human epithelial cell lines. Human uterine (ECC-1), colonic (CaCo-2), and retinal pigment (ARPE-19) epithelial cells were grown on collagen-coated inserts, and the polarity was monitored by measuring the transepithelial cell resistance. Controls were CaSki cells, a human cervical cell line that does not polarize in vitro. The polarized cells, but not CaSki cells, were 16- to 50-fold more susceptible to HSV infection at the apical surface than at the basolateral surface. Disruption of the tight junctions by treatment with EGTA overcame the restriction on basolateral infection but had no impact on apical infection. No differences in binding at the two surfaces were observed. Confocal microscopy demonstrated that nectin-1, the major coreceptor for HSV entry, sorted preferentially to the apical surface, overlapping with adherens and tight junction proteins. Transfection with small interfering RNA specific for nectin-1 resulted in a significant reduction in susceptibility to HSV at the apical surface but had little impact on basolateral infection. Infection from the apical but not the basolateral surface triggered focal adhesion kinase phosphorylation and led to nuclear transport of viral capsids and viral gene expression. These studies indicate that access to nectin-1 contributes to preferential apical infection of these human epithelial cells by HSV.
Preclinical Model To Test Human Papillomavirus Virus (HPV) Capsid Vaccines In Vivo Using Infectious HPV/Cottontail Rabbit Papillomavirus Chimeric Papillomavirus Particles
Authors: Mejia Andres F. , Culp Timothy D. , Cladel Nancy M. , Balogh Karla K. , Budgeon Lynn R. , Buck Christopher B. , Christensen Neil D. 
Published: November 2006

ABSTRACT
A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach.
Human Immunodeficiency Virus Type 1 Resistance to the Small Molecule Maturation Inhibitor 3-
O
-(3′,3′-Dimethylsuccinyl)-Betulinic Acid Is Conferred by a Variety of Single Amino Acid Substitutions at the CA-SP1 Cleavage Site in Gag
Authors: Zhou Jing , Chen Chin Ho , Aiken Christopher 
Published: November 2006

ABSTRACT

The compound 3-
O
-(3′,3′-dimethylsuccinyl)-betulinic acid (DSB) potently and specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired maturation of the viral core. In this study, we investigated HIV-1 resistance to DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid substitutions in the CA-SP1 cleavage site. Three of the substitutions were lethal to HIV-1 replication owing to a deleterious effect on particle assembly. The remaining mutants exhibited a range of replication efficiencies; however, each mutant was capable of replicating in the presence of concentrations of DSB that effectively inhibited wild-type HIV-1. Mutations conferring resistance to DSB also led to impaired binding of the compound to immature HIV-1 virions and loss of DSB-mediated inhibition of cleavage of Gag. Surprisingly, two of the DSB-resistant mutants retained an intermediate ability to bind the compound, suggesting that binding of DSB to immature HIV-1 particles may not be sufficient for antiviral activity. Overall, our results indicate that Gag amino acids L363 and A364 are critical for inhibition of HIV-1 replication by DSB and suggest that these residues form key contacts with the drug in the context of the assembling HIV-1 particle. These results have implications for the design of and screening for novel inhibitors of HIV-1 maturation.
Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Viral Attachment to Cells
Authors: Jones Jeremy C. , Turpin Elizabeth A. , Bultmann Hermann , Brandt Curtis R. , Schultz-Cherry Stacey 
Published: November 2006

ABSTRACT
Influenza A viruses continue to cause widespread morbidity and mortality. There is an added concern that the highly pathogenic H5N1 influenza A viruses, currently found throughout many parts of the world, represent a serious public health threat and may result in a pandemic. Intervention strategies to halt an influenza epidemic or pandemic are a high priority, with an emphasis on vaccines and antiviral drugs. In these studies, we demonstrate that a 20-amino-acid peptide (EB, for entry blocker) derived from the signal sequence of fibroblast growth factor 4 exhibits broad-spectrum antiviral activity against influenza viruses including the H5N1 subtype in vitro. The EB peptide was protective in vivo, even when administered postinfection. Mechanistically, the EB peptide inhibits the attachment to the cellular receptor, preventing infection. Further studies demonstrated that the EB peptide specifically binds to the viral hemagglutinin protein. This novel peptide has potential value as a reagent to study virus attachment and as a future therapeutic.
Antibody Recognition and Neutralization Determinants on Domains I and II of West Nile Virus Envelope Protein
Authors: Oliphant Theodore , Nybakken Grant E. , Engle Michael , Xu Qing , Nelson Christopher A. , Sukupolvi-Petty Soila , Marri Anantha , Lachmi Bat-El , Olshevsky Udy , Fremont Daved H. , Pierson Theodore C. , Diamond Michael S. 
Published: November 2006

ABSTRACTPrevious studies have demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral surface of domain III (DIII) of the West Nile virus (WNV) envelope (E) strongly protect against infection in animals. Herein, we observed significantly less efficient neutralization by 89 MAbs that recognized domain I (DI) or II (DII) of WNV E protein. Moreover, in cells expressing Fc γ receptors, many of the DI- and DII-specific MAbs enhanced infection over a broad range of concentrations. Using yeast surface display of E protein variants, we identified 25 E protein residues to be critical for recognition by DI- or DII-specific neutralizing MAbs. These residues cluster into six novel and one previously characterized epitope located on the lateral ridge of DI, the linker region between DI and DIII, the hinge interface between DI and DII, and the lateral ridge, central interface, dimer interface, and fusion loop of DII. Approximately 45% of DI-DII-specific MAbs showed reduced binding with mutations in the highly conserved fusion loop in DII: 85% of these (34 of 40) cross-reacted with the distantly related dengue virus (DENV). In contrast, MAbs that bound the other neutralizing epitopes in DI and DII showed no apparent cross-reactivity with DENV E protein. Surprisingly, several of the neutralizing epitopes were located in solvent-inaccessible positions in the context of the available pseudoatomic model of WNV. Nonetheless, DI and DII MAbs protect against WNV infection in mice, albeit with lower efficiency than DIII-specific neutralizing MAbs.
Immunogenicity of Heterologous Recombinant Adenovirus Prime-Boost Vaccine Regimens Is Enhanced by Circumventing Vector Cross-Reactivity
Authors: Thorner Anna R. , Lemckert Angelique A. C. , Goudsmit Jaap , Lynch Diana M. , Ewald Bonnie A. , Denholtz Matthew , Havenga Menzo J. E. , Barouch Dan H. 
Published: November 2006

ABSTRACT
The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad subgroup D, including rAd49. However, the optimal combination of vectors for heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have shown previously that the closely related vectors rAd11 and rAd35 elicited low levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs correlated with substantial sequence homology in the hexon hypervariable regions (HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These data suggest that optimal heterologous rAd prime-boost regimens should include two vectors that are both rare in human populations to circumvent preexisting antivector immunity as well as sufficiently immunologically distinct to avoid cross-reactive antivector immunity.