bluuebunny/crossref_metadata_2025_split huggingface dataset:
RUNX1 Permits E4orf6-Directed Nuclear Localization of the Adenovirus E1B-55K Protein and Associates with Centers of Viral DNA and RNA Synthesis
Authors: Marshall Leslie J. , Moore Amy C. , Ohki Misao , Kitabayashi Issay , Patterson David , Ornelles David A. 
Published: April 2008

ABSTRACT

The localization of the adenovirus E1B-55K-E4orf6 protein complex is critical for its function. Prior studies demonstrated that E4orf6 directs the nuclear localization of E1B-55K in human cells and in rodent cells that contain part of human chromosome 21. We show here that the relevant activity on chromosome 21 maps to
RUNX1
. RUNX1 proteins are transcription factors that serve as scaffolds for the assembly of proteins that regulate transcription and RNA processing. After transfection, the RUNX1a, RUNX1b, and RUNX1-ΔN variants allowed E4orf6-directed E1B-55K nuclear localization. The failure of RUNX1c to allow nuclear colocalization was relieved by the deletion of amino-terminal residues of this protein. In the adenovirus-infected mouse cell, RUNX1 proteins were localized to discrete structures about the periphery of viral replication centers. These sites are enriched in viral RNA and RNA-processing factors. RUNX1b and RUNX1a proteins displaced E4orf6 from these sites. The association of E1B-55K at viral replication centers was enhanced by the RUNX1a and RUNX1b proteins, but only in the absence of E4orf6. In the presence of E4orf6, E1B-55K occurred in a perinuclear cytoplasmic body resembling the aggresome and was excluded from the nucleus of the infected mouse cell. We interpret these findings to mean that a dynamic relationship exists between the E4orf6, E1B-55K, and RUNX1 proteins. In cooperation with E4orf6, RUNX1 proteins are able to modulate the localization of E1B-55K and even remodel virus-specific structures that form at late times of infection. Subsequent studies will need to determine a functional consequence of the interaction between E4orf6, E1B-55K, and RUNX1.
Porcine Rotavirus Bearing an Aberrant Gene Stemming from an Intergenic Recombination of the NSP2 and NSP5 Genes Is Defective and Interfering
Authors: Cao Dianjun , Barro Mario , Hoshino Yasutaka 
Published: April 2008

ABSTRACT
Serial undiluted passage of a porcine rotavirus in MA104 cells yielded three distinct virus populations, each of which bore different rearranged genes. Sequencing revealed that each of two populations bore a distinct intragenic recombinant NSP3 gene consisting of a partial duplication in a head-to-tail orientation without altering the NSP3 open reading frame and the third population carried both an intragenic recombinant NSP3 gene and an intergenic recombinant gene (1,647 nucleotides in length) which contained a truncated NSP2 gene inserted into the NSP5 gene at residue 332. The former two populations were viable, whereas the latter population was defective and interfering.
Antibody Is Critical for the Clearance of Murine Norovirus Infection
Authors: Chachu Karen A. , Strong David W. , LoBue Anna D. , Wobus Christiane E. , Baric Ralph S. , Virgin Herbert W. 
Published: April 2008

ABSTRACT

Human noroviruses cause more than 90% of epidemic nonbacterial gastroenteritis. However, the role of B cells and antibody in the immune response to noroviruses is unclear. Previous studies have demonstrated that human norovirus specific antibody levels increase upon infection, but they may not be protective against infection. In this report, we used murine norovirus (MNV), an enteric norovirus, as a model to determine the importance of norovirus specific B cells and immune antibody in clearance of norovirus infection. We show here that mice genetically deficient in B cells failed to clear primary MNV infection as effectively as wild-type mice. In addition, adoptively transferred immune splenocytes derived from B-cell-deficient mice or antibody production-deficient mice were unable to efficiently clear persistent MNV infection in RAG1
−/−
mice. Further, adoptive transfer of either polyclonal anti-MNV serum or neutralizing anti-MNV monoclonal antibodies was sufficient to reduce the level of MNV infection both systemically and in the intestine. Together, these data demonstrate that antibody plays an important role in the clearance of MNV and that immunoglobulin G anti-norovirus antibody can play an important role in clearing mucosal infection.
A Single
Banana Streak Virus
Integration Event in the Banana Genome as the Origin of Infectious Endogenous Pararetrovirus
Authors: Gayral Philippe , Noa-Carrazana Juan-Carlos , Lescot Magali , Lheureux Fabrice , Lockhart Benham E. L. , Matsumoto Takashi , Piffanelli Pietro , Iskra-Caruana Marie-Line 
Published: April 2008

ABSTRACT

Sequencing of plant nuclear genomes reveals the widespread presence of integrated viral sequences known as endogenous pararetroviruses (EPRVs). Banana is one of the three plant species known to harbor infectious EPRVs.
Musa balbisiana
carries integrated copies of
Banana streak virus
(BSV), which are infectious by releasing virions in interspecific hybrids. Here, we analyze the organization of the EPRV of BSV Goldfinger (BSGfV) present in the wild diploid
M. balbisiana
cv. Pisang Klutuk Wulung (PKW) revealed by the study of
Musa
bacterial artificial chromosome resources and interspecific genetic cross. cv. PKW contains two similar EPRVs of BSGfV. Genotyping of these integrants and studies of their segregation pattern show an allelic insertion. Despite the fact that integrated BSGfV has undergone extensive rearrangement, both EPRVs contain the full-length viral genome. The high degree of sequence conservation between the integrated and episomal form of the virus indicates a recent integration event; however, only one allele is infectious. Analysis of BSGfV EPRV segregation among an F1 population from an interspecific genetic cross revealed that these EPRV sequences correspond to two alleles originating from a single integration event. We describe here for the first time the full genomic and genetic organization of the two EPRVs of BSGfV present in cv. PKW in response to the challenge facing both scientists and breeders to identify and generate genetic resources free from BSV. We discuss the consequences of this unique host-pathogen interaction in terms of genetic and genomic plant defenses versus strategies of infectious BSGfV EPRVs.
Identification of a Critical Motif for the Human Immunodeficiency Virus Type 1 (HIV-1) gp41 Core Structure: Implications for Designing Novel Anti-HIV Fusion Inhibitors
Authors: He Yuxian , Cheng Jianwei , Li Jingjing , Qi Zhi , Lu Hong , Dong Mingxin , Jiang Shibo , Dai Qiuyun 
Published: April 2008

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) entry into the host cell involves a cascade of events and currently represents one of most attractive targets in the search for new antiviral drugs. The fusion-active gp41 core structure is a stable six-helix bundle (6-HB) folded by its trimeric N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR). Peptides derived from the CHR region of HIV-1 gp41 are potent fusion inhibitors that target the NHR to block viral and cellular membrane fusion in a dominant negative fashion. However, all CHR peptides reported to date are derived primarily from residues 628 to 673 of gp41; little attention has been paid to the upstream sequence of the pocket binding domain (PBD) in the CHR. Here, we have identified a motif (621QIWNNMT627) located at the upstream region of the gp41 CHR, immediately adjacent to the PBD (628WMEWEREI635). Biophysical characterization demonstrated that this motif is critical for the stabilization of the gp41 6-HB core. The peptide CP621-652, containing the621QIWNNMT627motif, was able to interact with T21, a counterpart peptide derived from the NHR, to form a typical 6-HB structure with a high thermostability (thermal unfolding transition [Tm] value of 82°C). In contrast, the 6-HB formed by the peptides N36 and C34, which has been considered to be a core structure of the fusion-active gp41, had aTmof 64°C. Different from T-20 (brand name Fuseon), which is the first and only HIV-1 fusion inhibitor approved for clinical use, CP621-652 could efficiently block 6-HB formation in a dose-dependent manner. Significantly, CP621-652 had potent inhibitory activity against HIV-1-mediated cell-cell fusion and infection, especially against T-20- and C34-resistant virus. Therefore, our works provide important information for understanding the core structure of the fusion-active gp41 and for designing novel anti-HIV peptides.
Henipavirus
V Protein Association with Polo-Like Kinase Reveals Functional Overlap with STAT1 Binding and Interferon Evasion
Authors: Ludlow Louise E. , Lo Michael K. , Rodriguez Jason J. , Rota Paul A. , Horvath Curt M. 
Published: April 2008

ABSTRACT

Emerging viruses in the paramyxovirus genus
Henipavirus
evade host antiviral responses via protein interactions between the viral V and W proteins and cellular STAT1 and STAT2 and the cytosolic RNA sensor MDA5. Polo-like kinase (PLK1) is identified as being an additional cellular partner that can bind to Nipah virus P, V, and W proteins. For both Nipah virus and Hendra virus, contact between the V protein and the PLK1 polo box domain is required for V protein phosphorylation. Results indicate that PLK1 is engaged by Nipah virus V protein amino acids 100 to 160, previously identified as being the STAT1 binding domain responsible for host interferon (IFN) signaling evasion, via a Thr-Ser-Ser-Pro motif surrounding residue 130. A distinct Ser-Thr-Pro motif surrounding residue 199 mediates the PLK1 interaction with Hendra virus V protein. Select mutations in the motif surrounding residue 130 also influenced STAT1 binding and innate immune interference, and data indicate that the V:PLK1 and V:STAT complexes are V mediated yet independent of one another. The effects of STAT1/PLK1 binding motif mutations on the function the Nipah virus P protein in directing RNA synthesis were tested. Remarkably, mutations that selectively disrupt the STAT or PLK1 interaction site have no effects on Nipah virus P protein-mediated viral RNA synthesis. Therefore, mutations targeting V protein-mediated IFN evasion will not alter the RNA synthetic capacity of the virus, supporting an attenuation strategy based on disrupting host protein interactions.
Rotavirus Infection Accelerates Type 1 Diabetes in Mice with Established Insulitis
Authors: Graham Kate L. , Sanders Natalie , Tan Yan , Allison Janette , Kay Thomas W. H. , Coulson Barbara S. 
Published: April 2008

ABSTRACTInfection modulates type 1 diabetes, a common autoimmune disease characterized by the destruction of insulin-producing islet β cells in the pancreas. Childhood rotavirus infections have been associated with exacerbations in islet autoimmunity. Nonobese diabetic (NOD) mice develop lymphocytic islet infiltration (insulitis) and then clinical diabetes, whereas NOD8.3 TCR mice, transgenic for a T-cell receptor (TCR) specific for an important islet autoantigen, show more rapid diabetes onset. Oral infection of infant NOD mice with the monkey rotavirus strain RRV delays diabetes development. Here, the effect of RRV infection on diabetes development once insulitis is established was determined. NOD and NOD8.3 TCR mice were inoculated with RRV aged ≥12 and 5 weeks, respectively. Diabetes onset was significantly accelerated in both models (P< 0.024), although RRV infection was asymptomatic and confined to the intestine. The degree of diabetes acceleration was related to the serum antibody titer to RRV. RRV-infected NOD mice showed a possible trend toward increased insulitis development. Infected males showed increased CD8+T-cell proportions in islets. Levels of β-cell major histocompatibility complex class I expression and islet tumor necrosis factor alpha mRNA were elevated in at least one model. NOD mouse exposure to mouse rotavirus in a natural experiment also accelerated diabetes. Thus, rotavirus infection after β-cell autoimmunity is established affects insulitis and exacerbates diabetes. A possible mechanism involves increased exposure of β cells to immune recognition and activation of autoreactive T cells by proinflammatory cytokines. The timing of infection relative to mouse age and degree of insulitis determines whether diabetes onset is delayed, unaltered, or accelerated.
Hepatitis C Virus (HCV)-Induced Immunoglobulin Hypermutation Reduces the Affinity and Neutralizing Activities of Antibodies against HCV Envelope Protein
Authors: Machida Keigo , Kondo Yasuteru , Huang Jeffrey Y. , Chen Yung-Chia , Cheng Kevin T.-H. , Keck Zhenyong , Foung Steven , Dubuisson Jean , Sung Vicky M.-H. , Lai Michael M. C. 
Published: April 2008

ABSTRACT

Hepatitis C virus (HCV) often causes persistent infection despite the presence of neutralizing antibodies against the virus in the sera of hepatitis C patients. HCV infects both hepatocytes and B cells through the binding of its envelope glycoprotein E2 to CD81, the putative viral receptor. Previously, we have shown that E2-CD81 interaction induces hypermutation of heavy-chain immunoglobulin (
V

H

) in B cells. We hypothesize that if HCV infects antibody-producing B cells, the resultant hypermutation of

V
H

may lower the affinity and specificity of the HCV-specific antibodies, enabling HCV to escape from immune surveillance. To test this hypothesis, we infected human hybridoma clones producing either neutralizing or non-neutralizing anti-E2 or anti-E1 antibodies with a lymphotropic HCV (SB strain). All of the hybridoma clones, except for a neutralizing antibody-producing hybridoma, could be infected with HCV and support virus replication for at least 8 weeks after infection. The

V
H

sequences in the infected hybridomas had a significantly higher mutation frequency than those in the uninfected hybridomas, with mutations concentrating in complementarity-determining region 3. These mutations lowered the antibody affinity against the targeting protein and also lowered the virus-neutralizing activity of anti-E2 antibodies. Furthermore, antibody-mediated complement-dependent cytotoxicity with the antibodies secreted from the HCV-infected hybridomas was impaired. These results suggest that HCV infection could cause some anti-HCV-antibody-producing hybridoma B cells to make less-protective antibodies.
Cytomegalovirus Proteins vMIA and m38.5 Link Mitochondrial Morphogenesis to Bcl-2 Family Proteins
Authors: Norris Kristi L. , Youle Richard J. 
Published: April 2008

ABSTRACT
Apoptosis is a host defense mechanism against viruses that can be subverted by viral gene products. Human cytomegalovirus encodes viral mitochondria-localized inhibitor of apoptosis (vMIA; also known as pUL37x1), which is targeted to mitochondria and functions as a potent cell death suppressor by binding to and inhibiting proapoptotic Bcl-2 family members Bax and Bak. vMIA expression also dramatically alters mitochondrial morphology, causing the fragmentation of these organelles. A potential ortholog of vMIA, m38.5, which was identified in murine cytomegalovirus, has been shown to localize to mitochondria and protect against chemically induced apoptosis by unknown mechanisms. Despite sharing negligible homology with vMIA and no region detectably corresponding to the vMIA Bax-binding domain, we find that m38.5, like vMIA, binds to Bax and recruits Bax to mitochondria. Interestingly, m38.5 and vMIA appear to block Bax downstream of translocation to mitochondria and after an initial stage of Bax conformational change. In contrast to vMIA, m38.5 neither binds to Bak nor causes mitochondrial fragmentation. Consistently with Bax-selective inactivation by m38.5, m38.5 fragments mitochondria in Bak knockout (KO) cells and protects Bak KO cells from apoptosis better than Bax KO cells. Thus, vMIA and m38.5 share some, but not all, features of apoptosis regulation through Bcl-2 family interaction and allow the dissection of Bax translocation into discrete steps.
Occupation and male infertility: glycol ethers and other exposures
Authors: Cherry N , Moore H , McNamee R , Pacey A , Burgess G , Clyma J-A , Dippnall M , Baillie H , Povey A ,   participating centres of Chaps-UK
Published: April 2008

Objectives:To investigate the relation between male infertility and occupational exposures, particularly glycol ethers.Methods:A case-referent study was designed in which men attending 14 fertility clinics in 11 centres across the UK in 1999–2002 were recruited following 12 months of unprotected intercourse and without a previous semen analysis. Cases were those with low motile sperm concentration (MSC) relative to the time since their last ejaculation (MSC <12×106 for 3 days of abstinence). Referents were other men attending these clinics and meeting the inclusion criteria. A single semen sample was collected at the clinic and analysed at the andrology laboratory serving each hospital. Concentration was determined manually with motility assessed centrally from video recordings. Exposures and confounding factors were assessed from self-completed and nurse–interviewer questionnaires, completed prior to the results of the semen analysis. The occupational histories were assessed for exposures relative to UK norms by a team of occupational hygienists blind to case status.Results:Of 2118 men in employment at the time of the interview, 874 (41.3%) were cases. Work with organic solvents, particularly glycol ethers, in the 3 months before the first clinic visit was associated with the likelihood of low motile sperm count. Unadjusted odds ratios (OR) for moderate and high glycol ether exposure (compared with none) were 1.70 (95% CI: 1.11 to 2.61) and 2.54 (95% CI: 1.24 to 5.21). Adjustment for potential confounders (surgery to the testes, previous conception, wearing boxer shorts, drinking alcohol, employed in manual work) reduced the risk associated with glycol ether exposure: moderate OR = 1.46 (95% CI: 0.93 to 2.28), high OR = 2.25 (95% CI: 1.08 to 4.69). No other occupational risk factor was identified.Conclusions:Glycol ether exposure was related to low motile sperm count in men attending fertility clinics. This suggests that, at the time of the study, glycol ethers continued to be a hazard for male fertility.
Meta-analysis of benzene exposure and non-Hodgkin lymphoma: biases could mask an important association
Authors: Steinmaus C , Smith A H , Jones R M , Smith M T 
Published: April 2008

Objectives:Benzene is a widely recognised cause of leukaemia but its association with non-Hodgkin’s lymphoma (NHL) is less well established. The goal of this project is to review the current published literature on this association.Methods:We performed a meta-analysis of cohort and case-control studies of benzene exposure and NHL and a meta-analysis of NHL and refinery work, a potential source of benzene exposure.Results:In 22 studies of benzene exposure, the summary relative risk for NHL was 1.22 (95 CI 1.02 to 1.47; one-sided p value  0.01). When studies that likely included unexposed subjects in the “exposed” group were excluded, the summary relative risk increased to 1.49 (95 CI 1.12 to 1.97, n  13), and when studies based solely on self-reported work history were excluded, the relative risk rose to 2.12 (95 CI 1.11 to 4.02, n  6). In refinery workers, the summary relative risk for NHL in all 21 studies was 1.21 (95 CI 1.00 to 1.46; p  0.02). When adjusted for the healthy worker effect, this relative risk estimate increased to 1.42 (95 CI 1.19 to 1.69).Conclusions:The finding of elevated relative risks in studies of both benzene exposure and refinery work provides further evidence that benzene exposure causes NHL. In addition, the finding of increased relative risks after removing studies that included unexposed or lesser exposed workers in “exposed” cohorts, and increased relative risk estimates after adjusting for the healthy worker effect, suggest that effects of benzene on NHL might be missed in occupational studies if these biases are not accounted for.
Chronic health problems and risk of accidental injury in the workplace: a systematic literature review
Authors: Palmer K T , Harris E C , Coggon D 
Published: April 2008

Objectives:To investigate whether common important health conditions and their treatments increase risks of occupational injury.Methods:A systematic search was conducted of MEDLINE, EMBASE and PsycINFO databases from inception to November 2006 employing terms for occupational injury, medications, and a broad range of diseases and impairments. Papers related solely to driving, alcohol, or substance abuse were excluded, as were studies that did not allow analysis of injury risk. For each paper that was retrieved we abstracted standard information on the population, design, exposure(s), outcome(s), response rates, confounders and effect estimates; and rated the quality of information provided.Results:We found 38 relevant papers (33 study populations): 16 studies were of cross-sectional design, 13 were case-control and 4 were prospective. The overall quality was rated as excellent for only two studies. Most commonly investigated were problems of hearing (15 studies), mental health (11 studies) and vision (10 studies).For impaired hearing, neurotic illness, diabetes, epilepsy and use of sedating medication there were moderate positive associations with occupational injury (odds ratios 1.5–2.0), but there were major gaps in the evidence base. Studies covering vision did not present risks by category of eye disease; no evidence was found on psychotic illness; for diabetes, epilepsy and cardiovascular disease there were remarkably few papers; studies seldom distinguished risks by sub-category of external cause or anatomical site and nature of injury; and exposures and outcomes were mostly ascertained by self-report at a single time point, with a lack of clarity about exposure timings.Conclusion:Improved research is needed to define the risks of occupational injury arising from common health complaints and treatments. Such research should delineate exposures and outcomes in more detail, and ensure by design that the former precede the latter.
Defense Mechanisms of Arthropods. XI. The Structure, Function, and Phenolic Secretions of the Glands of a Chordeumoid Millipede and a Carabid Beetle
Authors: Eisner T. , Hurst J. J. , Meinwald J. 
Published: April 2008

In the course of exploratory field studies on arthropods with defensive
glands, we came across two species which emit a strong and
persistent phenolic odor when handled. One is a carabid beetle
(Chlaenius cordicollis Kirby), the other a chordeumoid millipede
[Abacion magnum (Loomis)]. The fact that both animals produce
repellent secretions is not surprising, since many other carabids and
millipedes are well known for their defensive glands. But the particular
phenolic odor possessed by these two species is unIike the odor of
any other arthropod secretion that has been studied (for a summary
of defensive secretions of arthropods see Roth and Eisner, 1962).The purpose of this paper is to report on the nature of the two
phenols involved, and to discuss the structure and mode of operation
of the glands, as well as their defensive effectiveness. Both species
were collected in the environs of Ithaca, N. Y. Abacion was from
leaf litter in deciduous woods, and Chlaenius from beneath rocks near
a creek bed. We had available for study ten specimens of Abaciorz
and about two dozen Chlaenius.