bluuebunny/crossref_metadata_2025_split huggingface dataset:
The H5N1 Influenza Virus NS Genes Selected after 1998 Enhance Virus Replication in Mammalian Cells
Authors: Twu Karen Y. , Kuo Rei-Lin , Marklund Jesper , Krug Robert M. 
Published: May 2007

ABSTRACT
The NS1A proteins of human influenza A viruses bind CPSF30, a cellular factor required for the processing of cellular pre-mRNAs, thereby inhibiting the production of all cellular mRNAs, including beta interferon mRNA. Here we show that the NS1A protein of the pathogenic H5N1 influenza A/Hong Kong/483/97 (HK97) virus isolated from humans has an intrinsic defect in CPSF30 binding. It does not bind CPSF30 in vitro and causes high beta interferon mRNA production and reduced virus replication in MDCK cells when expressed in a recombinant virus in which the other viral proteins are encoded by influenza A/Udorn/72. We traced this defect to the identities of amino acids 103 and 106 in the HK97 NS1A protein, which differ from the consensus amino acids, F and M, respectively, found in the NS1A proteins of almost all human influenza A virus strains. X-ray crystallography has shown that F103 and M106, which are not part of the CPSF30 binding pocket of the NS1A protein, stabilize the NS1A-CPSF30 complex. In contrast to the HK97 NS1A protein, the NS1A proteins of H5N1 viruses isolated from humans after 1998 contain F103 and M106 and hence bind CPSF30 in vitro and do not attenuate virus replication. The HK97 NS1A protein is less attenuating when expressed in a virus that also encodes the other internal HK97 proteins and under these conditions binds to CPSF30 to a substantial extent in vivo. Consequently, these internal HK97 proteins largely compensate for the absence of F103 and M106, presumably by stabilizing the NS1A-CPSF30 complex.
Adaptation of Borna Disease Virus to New Host Species Attributed to Altered Regulation of Viral Polymerase Activity
Authors: Ackermann Andreas , Staeheli Peter , Schneider Urs 
Published: May 2007

ABSTRACT
Borna disease virus (BDV) can persistently infect the central nervous system of a broad range of mammalian species. Mice are resistant to infections with primary BDV isolates, but certain laboratory strains can be adapted to replicate in mice. We determined the molecular basis of adaptation by studying mutations acquired by a cDNA-derived BDV strain during one brain passage in rats and three passages in mice. The adapted virus propagated efficiently in mouse brains and induced neurological disease. Its genome contained seven point mutations, three of which caused amino acid changes in the L polymerase (L1116R and N1398D) and in the polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either alone or in combination all showed enhanced multiplication speed in Vero cells, indicating improved intrinsic viral polymerase activity rather than adaptation to a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred replication competence of recombinant BDV in mice if introduced individually. Virus propagation in mouse brains was substantially enhanced if both L mutations were present simultaneously, but infection remained mostly nonsymptomatic. Only if all three amino acid substitutions were combined did BDV replicate vigorously and induce early disease in mice. Interestingly, the virulence-enhancing effect of the R66K mutation in P could be attributed to reduced negative regulation of polymerase activity by the viral X protein. Our data demonstrate that BDV replication competence in mice is mediated by the polymerase complex rather than the viral envelope and suggest that altered regulation of viral gene expression can favor adaptation to new host species.
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing
Authors: Kwun Hyun Jin , da Silva Suzane Ramos , Shah Ishita M. , Blake Neil , Moore Patrick S. , Chang Yuan 
Published: May 2007

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses.
Rates of Reactivation of Latent Herpes Simplex Virus from Mouse Trigeminal Ganglia Ex Vivo Correlate Directly with Viral Load and Inversely with Number of Infiltrating CD8+T Cells
Authors: Hoshino Yo , Pesnicak Lesley , Cohen Jeffrey I. , Straus Stephen E. 
Published: May 2007

ABSTRACTHerpes simplex viruses (HSV) reactivate at rates proportional to the viral loads in latently infected ganglia. However, these rates vary substantially among infected animals. We assessed whether the numbers of HSV-specific CD8+T cells infiltrating latently infected ganglia also affect reactivation rates and contribute to their variability. Following corneal infection of mice with HSV type 2 (HSV-2), we quantified the latent viral loads in dissociated trigeminal ganglia by real-time PCR, the numbers of infiltrating CD8+T cells by flow cytometry, and the rates of reactivation by the detection of cell-free virus released from ganglion cells cultured in 96-well plates. The reactivation rates correlated directly with the latent viral loads (P= 0.001) but did so more strongly (P= 10−7) when cultures were depleted of CD8+T cells. Reactivation rates were reduced in a dose-dependent fashion by adding back ganglion CD8+T cells to the cultures (P= 0.003). We related the latent viral loads, numbers of CD8+T cells, and reactivation rates by mathematical equations. The rates of reactivation predicted from latent viral loads and numbers of infiltrating CD8+T cells in dissociated ganglia correlated with the observed rates of reactivation (P= 0.04). The reactivation of HSV-2 from ganglia ex vivo is determined both by the latent viral load and the number of infiltrating CD8+T cells.
The N Terminus of the Herpes Simplex Virus Type 1 Triplex Protein, VP19C, Cannot Be Detected on the Surface of the Capsid Shell by Using an Antibody (Hemagglutinin) Epitope Tag
Authors: Solé Marieta , Perkins Edward M. , Frisancho Augusto , Huang Eugene , Desai Prashant 
Published: May 2007

ABSTRACT
The herpes simplex virus (HSV) triplex is a complex of three protein subunits, VP19C and a dimer of VP23 that is essential for capsid assembly. We have derived HSV-1 recombinant viruses that contain monomeric red fluorescent protein (mRFP1), a Flu hemagglutinin (HA) epitope, and a six-histidine tag fused to the amino terminus of VP19C. These viruses were capable of growth on Vero cells, indicating that the amino terminus of VP19C could tolerate these fusions. By use of immunoelectron microscopy methods, capsids that express VP19C-mRFP but not VP19C-HA were labeled with gold particles when incubated with the corresponding antibody. Our conclusion from the data is that a large tag at the N terminus of VP19C was sufficiently exposed on the capsid surface for polyclonal antibody reactivity, while the small HA epitope was inaccessible to the antibody. These data indicate that an epitope tag at the amino terminus of VP19C is not exposed at the capsid surface for reactivity to its antibody.
Human Immunodeficiency Virus Type 1 Assembly, Budding, and Cell-Cell Spread in T Cells Take Place in Tetraspanin-Enriched Plasma Membrane Domains
Authors: Jolly Clare , Sattentau Quentin J. 
Published: May 2007

ABSTRACT

Human immunodeficiency virus type-1 (HIV-1) egress from infected CD4
+
T cells is thought to be via assembly and budding at the plasma membrane and may involve components of the T-cell secretory apparatus, including tetraspanins. However, many studies on HIV-1 assembly have examined the trafficking of viral proteins in isolation, and most have used immortalized epithelial, fibroblastic, or hematopoietic cell lines that may not necessarily reflect natural infection of susceptible T cells. Here we have used immunofluorescence and cryoimmunoelectron microscopy (CEM) to examine protein transport during HIV-1 assembly in productively infected Jurkat CD4
+
T cells and primary CD4
+
T cells. The HIV-1 envelope glycoprotein (Env) and the core protein (Gag) colocalize strongly with CD63 and CD81 and less strongly with CD9, whereas no colocalization was seen between Env or Gag and the late endosome/lysosomal marker Lamp2. CEM revealed incorporation of CD63 and CD81 but not Lamp2 into virions budding at the plasma membrane, and this was supported by immunoprecipitation studies, confirming that HIV-1 egress in T cells is trafficked via tetraspanin-enriched membrane domains (TEMs) that are distinct from lysosomal compartments. CD63, CD81, and, to a lesser extent, CD9 were recruited to the virological synapse (VS), and antibodies against these tetraspanins reduced VS formation. We propose that HIV-1 promotes virus assembly and cell-cell transfer in T cells by targeting plasma membrane TEMs.
Vif Counteracts a Cyclophilin A-Imposed Inhibition of Simian Immunodeficiency Viruses in Human Cells
Authors: Takeuchi Hiroaki , Buckler-White Alicia , Goila-Gaur Ritu , Miyagi Eri , Khan Mohammad A. , Opi Sandrine , Kao Sandra , Sokolskaja Elena , Pertel Thomas , Luban Jeremy , Strebel Klaus 
Published: May 2007

ABSTRACT

Vif is a primate lentiviral accessory protein that is crucial for viral infectivity. Vif counteracts the antiviral activity of host deaminases such as APOBEC3G and APOBEC3F. We now report a novel function of African green monkey simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in human cells lacking detectable deaminase activity. We found that cyclophilin A (CypA) was excluded from wild-type SIV particles but was efficiently packaged into
vif
-deficient SIVagm virions. The presence of CypA in
vif
-defective SIVagm was correlated with reduced viral replication. Infection of CypA knockout Jurkat cells or treatment of Jurkat cells with cyclosporine A eliminated the Vif-sensitive inhibition and resulted in replication profiles that were similar for wild-type and
vif
-deficient SIVagm. Importantly, the inhibitory effect of CypA was restricted to virus-producing cells and was TRIM5α independent. The abilities of SIVagm Vif to inhibit encapsidation of CypA and to increase viral infectivity were shared by rhesus macaque SIV Vif and thus seem to be general properties of SIV Vif proteins. Exclusion of CypA from SIVagm particles was not associated with intracellular degradation, suggesting a mode of Vif action distinct from that proposed for APOBEC3G. This is the first report of a novel
vif
-sensitive antiviral activity of human CypA that may limit zoonotic transmission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunodeficiency virus type 1.
Natural Variation in the V3 Crown of Human Immunodeficiency Virus Type 1 Affects Replicative Fitness and Entry Inhibitor Sensitivity
Authors: Lobritz Michael A. , Marozsan Andre J. , Troyer Ryan M. , Arts Eric J. 
Published: May 2007

ABSTRACTNatural polymorphisms in the heterogeneous human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein may have an impact on both sensitivity to entry inhibitors and viral replicative fitness. Of significant interest is variation in the V3 crown due to its involvement in direct engagement with the coreceptor. Two positions in the crown (318 and 319) appear to be important in determining intrinsic susceptibility to multiple entry inhibitors. Thus, we evaluated a series of natural polymorphisms at positions 318 and 319 in three distinct CCR5-tropic envelope genetic backgrounds to address their role in replicative fitness and sensitivity to entry inhibitors. Change at position 319 to each of the three major consensus amino acids (A, T, and R) resulted in variation in sensitivity to entry inhibitors and altered replicative fitness, but the effects of any one amino acid depended on the envelope context. Change of the nearly invariant tyrosine at position 318 to a rare arginine resulted in increased sensitivity to entry inhibitors and decreased replicative fitness independent of envelope context. Polymorphisms in the V3 crown that showed increased susceptibility to entry inhibitors also exhibited decreased entry efficiency, replicative fitness in primary peripheral blood mononuclear cells, and ability to replicate in primary macrophages. These findings suggest that differences in coreceptor affinity and/or avidity may underlie these phenotypic characteristics.
Susceptibility of Recently Transmitted Subtype B Human Immunodeficiency Virus Type 1 Variants to Broadly Neutralizing Antibodies
Authors: Quakkelaar Esther D. , van Alphen Floris P. J. , Boeser-Nunnink Brigitte D. M. , van Nuenen Ad C. , Pantophlet Ralph , Schuitemaker Hanneke 
Published: May 2007

ABSTRACT
The ability of the broadly neutralizing human immunodeficiency virus type 1 (HIV-1) specific human monoclonal antibodies (MAbs) b12, 2G12, 2F5, and 4E10 to neutralize recently transmitted viruses has not yet been explored in detail. We investigated the neutralization sensitivity of subtype B HIV-1 variants obtained from four primary HIV infection cases and six transmission couples (four homosexual and two parenteral) to these MAbs. Sexually transmitted HIV-1 variants isolated within the first 2 months after seroconversion were generally sensitive to 2F5, moderately resistant to 4E10 and b12, and initially resistant but later more sensitive to 2G12 neutralization. In the four homosexual transmission couples, MAb neutralization sensitivity of HIV in recipients did not correlate with the MAb neutralization sensitivity of HIV from their source partners, whereas the neutralization sensitivity of donor and recipient viruses involved in parenteral transmission was more similar. For a fraction (11%) of the HIV-1 variants analyzed here, neutralization by 2G12 could not be predicted by the presence of N-linked glycosylation sites previously described to be involved in 2G12 binding. Resistance to 2F5 and 4E10 neutralization did also not correlate with mutations in the respective core epitopes. Overall, we observed that the neutralization resistance of recently transmitted subtype B HIV-1 variants was relatively high. Although 8 of 10 patients had viruses that were sensitive to neutralization by at least one of the four broadly neutralizing antibodies studied, 4 of 10 patients harbored at least one virus variant that seemed resistant to all four antibodies. Our results suggest that vaccine antigens that only elicit antibodies equivalent to b12, 2G12, 2F5, and 4E10 may not be sufficient to protect against all contemporary HIV-1 variants and that additional cross-neutralizing specificities need to be sought.
Effects of training to implement new working methods to reduce knee strain in floor layers. A two-year follow-up
Authors: Jensen L K , Friche C 
Published: May 2007

Objectives:Follow-up study after two years to measure the effects of an implementation strategy consisting of information, education and training in the use of new tools and working-methods for the purpose of reducing knee strain and knee complaints in floor layers.Methods:Training of floor layers (n = 292) in using new working methods was evaluated by questionnaires during the courses. Two years later, this follow-up included questionnaires for the course participants (n = 216) and a control group of floor layers (not trained on courses) (n = 454).Results:Two years after training, 38% used the new working methods weekly or daily compared to 37% three months after the courses, and 10% before. Among controls, only 16% had used the new working methods weekly or daily. The risk of knee complaints >30 days (OR 2.46, 95% CI 1.03 to 5.83) or locking of the knees (OR 2.89, 95% CI 1.11 to 7.5) was more than double among floor layers who had used the new working-methods for less than one year compared to those who had used them more. The results were adjusted for age, body mass index, and stress. The reduction in more severe knee complaints was greatest if floor layers started to use the new working methods before they developed knee problems. Other musculoskeletal complaints did not increase.Conclusion:This indicates that, within a two-year perspective, the implementation strategy to introduce new working methods in the floor laying trade has been effective; the number of floor layers using the new working-methods has increased, and severe knee problems have reduced.
Prognostic factors for work ability in sicklisted employees with chronic diseases
Authors: Slebus Frans G , Kuijer P Paul F M , Willems J (Han) H B M , Sluiter Judith K , Frings-Dresen Monique H W 
Published: May 2007

Objective:Identifying prognostic factors for work ability in sicklisted employees with myocardial infarction (MI), chronic low back pain (cLBP) and major depressive disorder (MDD) in order to establish an objective basis for work ability evaluation.Design:Systematic literature search in PubMed database (1 January 1990 to 1 July 2006) with the Yale prognostic research filter. Inclusion criteria were as follows: (1) work-disabled employees; (2) MI, cLBP or MDD patients; (3) longitudinal designs; and (4) return to work or compensation status as outcome measure.Results:Four studies on MI met the inclusion criteria and described the following prognostic factors for work ability in the acute phase of the disease and disablement: lower age; male gender; no financial basis on which to retire; lower physical job demands; fewer somatic complaints; no anxiety attacks; no diabetes; no heart failure; no atrial fibrillation; no Q waves; and a short time interval between MI and presentation at the occupational medicine clinic. Two studies on cLBP met the inclusion criteria and described the following prognostic factors for work ability after 3 months’ work disablement: lower age; male gender; no treatment before sick listing; surgery in the first year of sick listing; being a breadwinner; less pain; better general health; higher job satisfaction; lower physical and/or psychological demands at work; and a higher decision latitude at work. No relevant MDD studies were found.Conclusion:In the earlier phases of work disablement in MI and cLBP patients, only a few studies describe disease-specific, environmental and personal prognostic factors for return to work. No studies describe prognostic factors for MDD. More evidence is needed on the topic of prognostic factors for return to work in employees with chronic diseases.
Media oracles
Authors: Neiger Motti 
Published: May 2007

As noted by Jaworski et al. (2003a, 2003b, 2004), a significant amount of news items refer to future events. This article examines the `discourse of the future' in order to identify its extent and different types. The research examined headlines in Israeli newspapers over a period of 18 years (1985—2003) and found that approximately 70 percent of the main headlines deal not only with past events but with future ones as well. Thus, contrary to the conventional perception of journalism, this type of journalism does not report what has already happened, but speculates on future events, whether directly or by quoting military or political figures. The qualitative analysis suggests four types of discourse of the future: Predictable Future, Informed Assessment, Speculative Assessment, and Conjectured Future. During the last two decades, we can witness a gradual rise of speculation levels. `The discourse of the future' carries cultural significance and political import. From the cultural standpoint, journalists encourage us to raise questions regarding the future of the community: What will happen next? Where do we go from here, in the short, medium and long term? What are our hopes? What do we fear most? Nevertheless, in the highest levels of speculation, such discourse bears political import because it provides fertile ground for releasing trial balloons, magnifying threats, creating solidarity, and justifying acts of government.
Regeneration of neural crest derivatives in the Xenopustadpole tail
Authors: Lin Gufa , Chen Ying , Slack Jonathan MW 
Published: May 2007

AbstractBackgroundAfter amputation of theXenopustadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper.ResultsLabelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration.There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation.The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them.ConclusionOn regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.