bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Human Immunodeficiency Virus Type 1 Gene Expression by Clade-Specific Tat Proteins
Authors: Desfosses Yan , Solis Mayra , Sun Qiang , Grandvaux Nathalie , Van Lint Carine , Burny Arsene , Gatignol Anne , Wainberg Mark A. , Lin Rongtuan , Hiscott John 
Published: July 2005

ABSTRACT
The major group of human immunodeficiency virus type 1 (HIV-1) strains that comprise the current global pandemic have diversified during their worldwide spread into at least 10 distinct subtypes, or clades. Subtype C predominates in sub-Saharan Africa and is responsible for the majority of worldwide HIV-1 infections, subtype B predominates in North America and Europe, and subtype E is prevalent in Southeast Asia. Significant amino acid variations have been observed among the clade-specific Tat proteins. For the present study, we examined clade-specific interactions between Tat, transactivation-responsive (TAR) element, and P-TEFb proteins and how these interactions may modulate the efficiency of HIV-1 transcription. Clade-specific Tat proteins significantly modified viral gene expression. Tat proteins derived from HIV-1 clades C and E were strong transactivators of long terminal repeat (LTR) activity; Tat E also had a longer half-life than the other Tat proteins and interacted more efficiently with the stem-loop TAR element. Chimeric Tat proteins harboring the Tat E activation domain were strong transactivators of LTR expression. While Tat B, C, and E were able to rescue a Tat-defective HIV-1 proviral clone, Tat E was significantly more efficient at rescue than Tat C, possibly due to the relative stability of the Tat protein. Swapping the activation domains of Tat B, C, and E identified the cyclin T1 association domain as a critical determinant of the transactivation efficiency and of Tat-defective HIV-1 provirus rescue.
Mannose Binding Lectin Genotypes Influence Recovery from Hepatitis B Virus Infection
Authors: Thio Chloe L. , Mosbruger Timothy , Astemborski Jacquie , Greer Spencer , Kirk Gregory D. , O'Brien Stephen J. , Thomas David L. 
Published: July 2005

ABSTRACTMannose binding lectin (MBL) is a central component of the innate immune response and thus may be important for determining hepatitis B virus (HBV) persistence. Since single-nucleotide polymorphisms (SNPs) in the gene encoding MBL (mbl2) alter the level of functional MBL, we hypothesized thatmbl2genotypes are a determinant of HBV persistence or recovery from viral infection. We tested this hypothesis by using a nested case control design with 189 persons with HBV persistence matched to 338 individuals who had naturally recovered from HBV infection. We determined genotypes of two promoter and three exon 1 SNPs inmbl2and grouped these genotypes according to the amount of functional MBL production. We found that the promoter SNP −221C, which leads to deficient MBL production, was more common in those subjects with viral persistence (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.01 to 1.89;P= 0.04). Those subjects homozygous for the combination of promoter and exon 1 genotypes associated with the highest amount of functional MBL had significantly increased odds of recovery from infection (OR, 0.55; 95% CI, 0.37 to 0.84;P= 0.005). Conversely, those homozygous for the combination of promoter and exon 1 genotypes which produce the lowest amount of functional MBL were more likely to have viral persistence (OR, 1.76; 95% CI, 1.02 to 3.01;P= 0.04). These data are consistent with the hypothesis that functional MBL plays a central role in the pathogenesis of acute hepatitis B.
In Vitro Suppression of Human Immunodeficiency Virus Type 1 Replication by Measles Virus
Authors: García Mayra , Yu Xiao-Fang , Griffin Diane E. , Moss William J. 
Published: July 2005

ABSTRACTDuring the acute phase of measles, human immunodeficiency virus type 1 (HIV-1)-infected children have a transient, but dramatic, decrease in plasma HIV-1 RNA levels (W. J. Moss, J. J. Ryon, M. Monze, F. Cutts, T. C. Quinn, and D. E. Griffin, J. Infect. Dis.185:1035-1042, 2002). To determine the mechanism(s) by which coinfection with measles virus (MV) decreases HIV-1 replication, we established an in vitro culture system that reproduces this effect. The addition of MV to CCR5- or CXCR4-tropic HIV-1-infected human peripheral blood mononuclear cells (PBMCs) decreased HIV-1 p24 antigen production in a dose-dependent manner. This decrease occurred with the addition of MV before or after HIV-1. The inhibition of HIV-1 p24 antigen production was decreased when UV-inactivated MV or virus-free supernatant fluid from MV-infected PBMCs was used. Inhibition was not due to increased production of chemokines known to block coreceptor usage by HIV-1, a decrease in the percentage of CD4+T cells, or a decrease in chemokine receptor expression by CD4+T cells. Viability of PBMCs was decreased only 10 to 20% by MV coinfection; however, lymphocyte proliferation was decreased by 60 to 90% and correlated with decreased production of p24 antigen. These studies showed that an in vitro system of coinfected PBMCs could be used to dissect the mechanism(s) by which MV suppresses HIV-1 replication in coinfected children and suggest that inhibition of lymphocyte proliferation by MV may play a role in the suppression of HIV-1 p24 antigen production.
Propagation and Dissemination of Infection after Vaginal Transmission of Simian Immunodeficiency Virus
Authors: Miller Christopher J. , Li Qingsheng , Abel Kristina , Kim Eun-Young , Ma Zhong-Min , Wietgrefe Stephen , La Franco-Scheuch Lisa , Compton Lara , Duan Lijie , Shore Marta Dykhuizen , Zupancic Mary , Busch Marc , Carlis John , Wolinksy Steven , Haase Ashley T. 
Published: July 2005

ABSTRACT
In the current global AIDS pandemic, more than half of new human immunodeficiency virus type 1 (HIV-1) infections are acquired by women through intravaginal HIV exposure. For this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using an animal model in which female rhesus macaques were exposed intravaginally to a high dose of simian immunodeficiency virus (SIV). We examined in detail the events that transpire from hours to a few days after intravaginal SIV exposure through week 4 to provide a framework for understanding the propagation, dissemination, and establishment of infection in lymphatic tissues (LTs) during the acute stage of infection. We show that the mucosal barrier greatly limits the infection of cervicovaginal tissues, and thus the initial founder populations of infected cells are small. While there was evidence of rapid dissemination to distal sites, we also show that continuous seeding from an expanding source of production at the portal of entry is likely critical for the later establishment of a productive infection throughout the systemic LTs. The initially small founder populations and dependence on continuous seeding to establish a productive infection in systemic LTs define a small window of maximum vulnerability for the virus in which there is an opportunity for the host, vaccines, or other interventions to prevent or control infection.
CD8+T-Lymphocyte Response to Major Immunodominant Epitopes after Vaginal Exposure to Simian Immunodeficiency Virus: Too Late and Too Little
Authors: Reynolds Matthew R. , Rakasz Eva , Skinner Pamela J. , White Cara , Abel Kristina , Ma Zhong-Min , Compton Lara , Napoé Gnankang , Wilson Nancy , Miller Christopher J. , Haase Ashley , Watkins David I. 
Published: July 2005

ABSTRACTIn the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8+T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletion of CD4+T lymphocytes in gut-associated lymphatic tissue (GALT). We explored hypothetical explanations for this failure to clear infection and prevent CD4+T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal transmission. We examined the relationship between the timing and magnitude of the CD8+T-lymphocyte response to immunodominant SIV epitopes and viral replication, and we show first that the failure to contain infection is not because the female reproductive tract is a poor inductive site. We documented robust responses in cervicovaginal tissues and uterus, but only several days after the peak of virus production. Second, while we also documented a modest response in the draining genital and peripheral lymph nodes, the response at these sites also lagged behind peak virus production in these LT compartments. Third, we found that the response in GALT was surprisingly low or undetectable, possibly contributing to the severe and sustained depletion of CD4+T lymphocytes in the GALT. Thus, the virus-specific CD8+T-lymphocyte response is “too late and too little” to clear infection and prevent CD4+T-lymphocyte loss. However, the robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.
Protease-Dependent Uncoating of a Complex Retrovirus
Authors: Lehmann-Che Jacqueline , Giron Marie-Lou , Delelis Olivier , Löchelt Martin , Bittoun Patricia , Tobaly-Tapiero Joelle , de Thé Hugues , Saïb Ali 
Published: July 2005

ABSTRACT
Although retrovirus egress and budding have been partly unraveled, little is known about early stages of the replication cycle. In particular, retroviral uncoating, a process during which incoming retroviral cores are altered to allow the integration of the viral genome into host chromosomes, is poorly understood. To get insights into these early events of the retroviral cycle, we have used foamy complex retroviruses as a model. In this report, we show that a protease-defective foamy retrovirus is noninfectious, although it is still able to bud and enter target cells efficiently. Similarly, a retrovirus mutated in an essential viral protease-dependent cleavage site in the central part of Gag is noninfectious. Following entry, wild-type and mutant retroviruses are able to traffic along microtubules towards the microtubule-organizing center (MTOC). However, whereas nuclear import of Gag and of the viral genome was observed for the wild-type virus as early as 8 hours postinfection, incoming capsids and genome from mutant viruses remained at the MTOC. Interestingly, a specific viral protease-dependent Gag cleavage product was detected only for the wild-type retrovirus early after infection, demonstrating that cleavage of Gag by the viral protease at this stage of the virus life cycle is absolutely required for productive infection, an unprecedented observation among retroviruses.
Growth Suppression Induced by Downregulation of E6-AP Expression in Human Papillomavirus-Positive Cancer Cell Lines Depends on p53
Authors: Hengstermann Arnd , D'silva Michael A. , Kuballa Petric , Butz Karin , Hoppe-Seyler Felix , Scheffner Martin 
Published: July 2005

ABSTRACT
The ubiquitin-protein ligase E6-AP is utilized by the E6 oncoprotein of human papillomaviruses (HPVs) associated with cervical cancer to target the tumor suppressor p53 for degradation. Here, we report that downregulation of E6-AP expression by RNA interference results in both the accumulation of p53 and growth suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa. In addition, HeLa cells, in which p53 expression was suppressed by RNA interference, are significantly less sensitive to the downregulation of E6-AP expression with respect to growth suppression than parental HeLa cells. These data indicate that the anti-growth-suppressive properties of E6-AP in HPV-positive cells depend on its ability to induce p53 degradation.
Evidence of Recombination between Divergent Hepatitis E Viruses
Authors: van Cuyck Hélène , Fan Jun , Robertson David L. , Roques Pierre 
Published: July 2005

ABSTRACT
Phylogenetic and recombination analysis was performed on 32 complete hepatitis E virus (HEV) genomes from infected humans and pigs. For the first time, evidence for recombination between divergent HEV strains was obtained, with at least two strains being found to have discordant phylogenetic relationships consistent with the occurrence of intragenotype recombination. This finding confirms that humans can be dually infected with divergent HEV strains and has implications for the emergence and evolution of new HEV epidemics.
Identification of TRAIL as an Interferon Regulatory Factor 3 Transcriptional Target
Authors: Kirshner Jessica R. , Karpova Alla Y. , Kops Maren , Howley Peter M. 
Published: July 2005

ABSTRACTInterferon production and apoptosis in virus-infected cells are necessary to prevent progeny virus production and to eliminate infected cells. Paramyxovirus infection induces apoptosis through interferon regulatory factor 3 (IRF-3), but the exact mechanism of how IRF-3 functions is unknown. We show that IRF-3 is involved in the transcriptional induction of TRAIL, a key player in the apoptosis pathway. IRF-3 upregulates TRAIL transcription following viral infection and binds an interferon-stimulated response element in the TRAIL promoter. The mRNA for TRAIL and its receptor, DR5, are induced following viral infection. These studies identify TRAIL as a novel IRF-3 transcriptional target.
Identification of Proteins Phosphorylated Directly by the Us3 Protein Kinase Encoded by Herpes Simplex Virus 1
Authors: Kato Akihisa , Yamamoto Mayuko , Ohno Takashi , Kodaira Hiroshi , Nishiyama Yukihiro , Kawaguchi Yasushi 
Published: July 2005

ABSTRACT
We have developed a system to analyze the specific protein kinase activity of herpes simplex virus 1 Us3 in vitro and shown that Us3 directly phosphorylates viral proteins UL34, ICP22, and Us9 and the cellular protein Bad, previously reported to be putative substrates. Using this system, we determined the phosphorylation sites of UL34 and identified UL31 as a previously unreported, novel substrate of Us3. This system will be useful for further identification of Us3 substrates and their phosphorylation sites, clarification of the role of Us3 in viral replication, and identification of additional Us3 function(s).
Dissection of Gammaretroviral Receptor Function by Using Type III Phosphate Transporters as Models
Authors: Farrell Karen B. , Eiden Maribeth V. 
Published: July 2005

ABSTRACT

Gammaretroviruses that enter cells via binding to a surface receptor use one of two fundamental mechanisms. In the first, binding of the virus particle to its cognate receptor is followed by fusion and internalization. The second, less common mechanism requires the addition of an accessory protein in order to achieve fusion and entry into the target cells; this protein is usually the soluble form of the envelope protein containing the receptor-binding domain (RBD). For some viruses, such as amphotropic murine leukemia virus (A-MLV), particles with fusion-defective envelope proteins can enter cells in the presence of their own RBD or that of another viral envelope, regardless of its cognate receptor, suggesting that these viruses share a common entry mechanism. A notable exception is gibbon ape leukemia virus (GALV). Fusion-impaired GALV envelope mutants can be
trans
-activated for infectivity only by GALV RBDs. Using dually functional GALV/A-MLV receptors, we examined the role of receptor with respect to which RBD could overcome fusion impaired virus entry.
Role of CXCR3 in the Immune Response to Murine Gammaherpesvirus 68
Authors: Lee Bong Joo , Giannoni Francesca , Lyon Ashley , Yada Shinichiro , Lu Bao , Gerard Craig , Sarawar Sally R. 
Published: July 2005

ABSTRACT

The chemokine IP-10 (CXCL10) and its cellular receptor CXCR3 are upregulated in the lung during murine gammaherpesvirus 68 (MHV-68) infection. In order to determine the role of the CXCR3 chemokine receptor in the immune response to MHV-68, CXCR3
−/−
mice were infected with the virus. CXCR3
−/−
mice showed delayed clearance of replicating MHV-68 from the lungs. This correlated with delayed T-cell recruitment to the lungs and reduced cytolytic activity prior to viral clearance. Splenomegaly and the numbers of latently infected cells per spleen were transiently increased. Ηowever, CXCR3
−/−
mice showed normal virus-specific antibody titers and effective long-term control of MHV-68 infection.
Intrapatient Escape in the A*0201-Restricted Epitope SLYNTVATL Drives Evolution of Human Immunodeficiency Virus Type 1 at the Population Level
Authors: Edwards Charles T. T. , Pfafferott Katja J. , Goulder Philip J. R. , Phillips Rodney E. , Holmes Edward C. 
Published: July 2005

ABSTRACT

The hypothesis that the intrapatient emergence of cytotoxic T-lymphocyte escape variants contributes to the evolution of human immunodeficiency virus type 1 at the population (interpatient) level was tested using the HLA-A*0201-restricted
gag p17
epitope SLYNTVATL. Using a simple experimental design, we investigated the evolutionary processes operating within this epitope among patients while compensating for the confounding influence of intrapatient natural selection. Using this approach, we revealed a pattern of A*0201-driven escape within patients, followed by the sustained transmission of these escape variants among patients irrespective of their HLA type.
Justice and the NHS: a comment on Culyer
Authors: McLachlan H V 
Published: July 2005

The nature and significance of equity and equality in relation to health and healthcare policy is discussed in the light of a recent article by Culyer. Culyer makes the following claims: (a) the importance of equity in relation to the provision of health care derives from the human need for health in order to flourish; and (b) for the sake of equity, equality of health among the members of particular political jurisdictions should be the aim of health policy. Both these claims are challenged in this paper.The argument put forward is that it is only when needs arise and are met in particular contexts that need and equity are fused. The state and its agents and agencies should distribute what it distributes impartially, whatever it distributes. Whether or not equity applies to the distribution of healthcare services depends on how they are provided and not on their nature as “primary goods”. Contrary to what Culyer suggests, a policy of trying to produce the outcome of health equality would be inequitable. It would not be impartial and it would fail to treat persons as persons ought to be treated.
SIX-DIMENSIONAL DYNAMICS OF DISSOCIATIVE CHEMISORPTION OFH2ON METAL SURFACES
Authors: KROES GEERT-JAN , SOMERS MARK F. 
Published: July 2005

The theory of time-dependent quantum dynamics of dissociative chemisorption of hydrogen on metal surfaces is reviewed, in the framework of electronically adiabatic scattering from static surfaces. Four implementations of the time-dependent wave packet (TDWP) method are discussed. In the direct product pseudo-spectral and the spherical harmonics pseudo-spectral methods, no use is made of the symmetry associated with the surface unit cell. This symmetry is exploited by the symmetry adapted wave packet and the symmetry adapted pseudo-spectral (SAPS) method, which are efficient for scattering at normal incidence. The SAPS method can be employed for potential energy surfaces of general form.Comparison to experiment shows that the TDWP method yields good, but not yet excellent, quantitative accuracy for dissociation of (ν = 0, j = 0) H2if the calculations are based on accurately fitted density functional theory calculations that are performed using the generalized gradient approximation. The influence of the molecule's vibration (rotation) is well (reasonably well) described. The theory does not yet yield quantitatively accurate results for rovibrationally inelastic scattering. The theory has helped with the interpretation of existing experimental results, for instance, by solving a parodox regarding the corrugation of Pt(111) as seen by reacting and scattering H2. The theory has also provided some exciting new predictions, for instance, concerning where on the surface of Cu(100) H2reacts depending on its vibrational state. Future theoretical studies of H2reacting on metal surfaces will likely be aimed at validating GGAs for molecule-surface interactions, and understanding trends in collisions of H2with complex metal surfaces.
The English Fetus and the Right to Life
Authors: Scott Rosamund 
Published: July 2005

AbstractFollowing the enactment of the Human Rights Act 1998 in English law, there was speculation as to whether the English legal position that the fetus has no right to life is compatible with Article 2 of the European Convention on Human Rights (ECHR). The recent decision of the European Court of Human Rights in Vo v. France provides an opportunity to reflect on the current English and ECtHR approaches to the fetus. The problems of finding a fetal right to life, which Vo sidesteps, are noted. At the same time, the "all or nothingness" of rights language is not without difficulties and troubled the judges in Vo. In particular, the idea that the fetus has no right to life gives the impression that neither English nor ECHR law values the fetus. In this light, we find English and ECtHR judges trying to express a concern for the fetus which does not undermine a pregnant woman's legal interests. This article considers these issues and highlights the importance, in a highly genetic age, of developing ways of valuing the fetus without invoking the language of rights and thus without affecting the current legal balance of interests in the maternal-fetal relationship. The idea of valuing the fetus in this way is briefly explored with particular reference to aspects of selective abortion.
Problems of practice and principle if centring law reform on the concept of genetic discrimination
Authors: Taylor  
Published: July 2005

AbstractAdvances in genetic science are increasing the significance of genetic information within the contractual environment. While there may be an obligation upon governments to respond to this trend a number of problems may be associable with any attempt to do so that is centred on the concept of genetic discrimination as such. An attempt to exclusively limit regulatory reform to the acquisition and use of specifically genetic information may prove ultimately indefensible: the nature of genetic information is likely to render any such reform either ineffective or unworkable in practice or prove it arbitrary in principle.This position may be defended through a sustained look at what might conceivably be understood by the term 'genetic discrimination'. The term may, broadly speaking, be understood to refer to one of three kinds of discrimination. Tracing the conceptual contours of genetic discrimination in a primary, secondary and tertiary sense helps to illustrate potential regulatory difficulties of both principle and practice.If the identified practical problems are to be avoided then lines must be drawn not between the three 'kinds' of genetic discrimination described but rather through them. However, drawing a line through a particular concept of genetic discrimination (and of genetic information) involves undeniably excluding certain genetic information from the scope of the regulation.If an unblinking focus upon the concept of genetic information per se demonstrates the limits of this concept as a focus of legislative reform then questions are raised as to the significance of 'genetic' interpretation to the raison d'être of regulation. I conclude by proposing that, while advances in genetic science may provide the motivation, the most appropriate target of reform may not indeed be genetic information per se at all.