bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence of Hepatitis B Surface Antigen (HBs Ag) and Anti-HBs Antibodies in Chronic Hepatitis B Virus Carriers: Influence of “a” Determinant Variants
Authors: Lada Olivier , Benhamou Yves , Poynard Thierry , Thibault Vincent 
Published: February 2006

ABSTRACT

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the “a” determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (
P
= 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of “a” determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.
Dengue Virus Utilizes a Novel Strategy for Translation Initiation When Cap-Dependent Translation Is Inhibited
Authors: Edgil Dianna , Polacek Charlotta , Harris Eva 
Published: February 2006

ABSTRACTViruses have developed numerous mechanisms to usurp the host cell translation apparatus. Dengue virus (DEN) and other flaviviruses, such as West Nile and yellow fever viruses, contain a 5′ m7GpppN-capped positive-sense RNA genome with a nonpolyadenylated 3′ untranslated region (UTR) that has been presumed to undergo translation in a cap-dependent manner. However, the means by which the DEN genome is translated effectively in the presence of capped, polyadenylated cellular mRNAs is unknown. This report demonstrates that DEN replication and translation are not affected under conditions that inhibit cap-dependent translation by targeting the cap-binding protein eukaryotic initiation factor 4E, a key regulator of cellular translation. We further show that under cellular conditions in which translation factors are limiting, DEN can alternate between canonical cap-dependent translation initiation and a noncanonical mechanism that appears not to require a functional m7G cap. This DEN noncanonical translation is not mediated by an internal ribosome entry site but requires the interaction of the DEN 5′ and 3′ UTRs for activity, suggesting a novel strategy for translation of animal viruses.
RNase L Plays a Role in the Antiviral Response to West Nile Virus
Authors: Scherbik Svetlana V. , Paranjape Jayashree M. , Stockman Bronislava M. , Silverman Robert H. , Brinton Margo A. 
Published: February 2006

ABSTRACT

Alleles at the
Flv
locus determine disease outcome after a flavivirus infection in mice. Although comparable numbers of congenic resistant and susceptible mouse embryo fibroblasts (MEFs) are infected by the flavivirus West Nile virus (WNV), resistant MEFs produce ∼100- to 150-fold lower titers than susceptible ones and flavivirus titers in the brains of resistant and susceptible animals can differ by >10,000-fold. The
Flv
locus was previously identified as the 2′-5′ oligoadenylate synthetase 1b (
Oas1b
) gene.
Oas
gene expression is up-regulated by interferon (IFN), and after activation by double-stranded RNA, some mouse synthetases produce 2-5A, which activates latent RNase L to degrade viral and cellular RNAs. To determine whether the lower levels of intracellular flavivirus genomic RNA from resistant mice detected in cells at all times after infection were mediated by RNase L, RNase L activity levels in congenic resistant and susceptible cells were compared. Similar moderate levels of RNase L activation by transfected 2-5A were observed in both types of uninfected cells. After WNV infection, the mRNAs of IFN-β and three
Oas
genes were up-regulated to similar levels in both types of cells. However, significant levels of RNase L activity were not detected until 72 h after WNV infection and the patterns of viral RNA cleavage products generated were similar in both types of cells. When RNase L activity was down-regulated in resistant cells via stable expression of a dominant negative RNase L mutant, ∼5- to 10-times-higher yields of WNV were produced. Similarly, about ∼5- to 10-times-higher virus yields were produced by susceptible C57BL/6 RNase L
−/−
cells compared to RNase L
+/+
cells that were either left untreated or pretreated with IFN and/or poly(I) · poly(C). The data indicate that WNV genomic RNA is susceptible to RNase L cleavage and that RNase L plays a role in the cellular antiviral response to flaviviruses. The results suggest that RNase L activation is not a major component of the
Oas1b
-mediated flavivirus resistance phenotype.
Biological Relevance of a Stable Biochemical Interaction between the Tombusvirus-Encoded P19 and Short Interfering RNAs
Authors: Omarov Rustem , Sparks Kim , Smith Lindsay , Zindovic Jelena , Scholthof Herman B. 
Published: February 2006

ABSTRACT

The
Tomato bushy stunt virus
(TBSV)-encoded
p19
protein (P19) is widely used as a robust tool to suppress RNA interference (RNAi) in various model organisms. P19 dimers appropriate 21-nucleotide (nt) duplex short interfering RNAs (siRNAs) generated by Dicer presumably to prevent programming of the RNA-induced silencing complex (RISC). In the context of virus infection, this model predicts that P19 mutants compromised for siRNA binding cannot prevent RISC-mediated degradation of TBSV RNA and thus reduce viral pathogenicity. To test this, we used P19/43 (R→W), which is less pathogenic than wild-type P19 (wtP19), and P19/75-78 (RR→GG), with pathogenicity properties (i.e., viral spread and symptom induction) comparable to those of a P19-null mutant. We demonstrate that P19/43 still suppresses RNAi-mediated viral RNA degradation in infected
Nicotiana benthamiana
, while P19/75-78 is unable to prevent this clearance of viral RNA, leading to an irreversible recovery phenotype. Gel filtration and immunoprecipitation assays show that at the onset of the infection, wtP19, P19/43, and P19/75-78 readily accumulate, and they form dimers. The wtP19 is stably associated with duplex ∼21-nt TBSV siRNAs, while P19/75-78 does not bind these molecules, and the electrostatic interaction of P19/43 with siRNAs is perturbed for ∼21-nt duplexes but not for longer siRNAs. This is the first clear demonstration of a direct correlation between a novel structurally orchestrated siRNA binding of an RNAi suppressor and its roles in viral pathogenesis. The findings should be particularly valuable for the RNAi field in general because the P19 mutants enable precise determination of siRNA appropriation effects.
Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence
Authors: Kash John C. , Mühlberger Elke , Carter Victoria , Grosch Melanie , Perwitasari Olivia , Proll Sean C. , Thomas Matthew J. , Weber Friedemann , Klenk Hans-Dieter , Katze Michael G. 
Published: February 2006

ABSTRACT

We studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with Zaire
Ebolavirus
(ZEBOV), Reston
Ebolavirus
(REBOV), and
Marburgvirus
(MARV), using transcriptional profiling and bioinformatics. Expression microarray analysis demonstrated that filovirus infection resulted in the up-regulation of immune-related genes and the down-regulation of many coagulation and acute-phase proteins. These studies further revealed that a common feature of filovirus virulence is suppression of key cellular antiviral responses, including TLR-, interferon (IFN) regulatory factor 3-, and PKR-related pathways. We further showed that ZEBOV and MARV were more potent antagonists of the IFN response and inhibited the expression of most of the IFN-stimulated genes (ISGs) observed in mock-infected IFN-α-2b treated cells, compared to REBOV infection, which activated more than 20% of these ISGs. Finally, we examined IFN-related gene expression in filovirus-infected cells treated with IFN-α-2b. These experiments revealed that a majority of genes induced in mock-infected cells treated with type I IFN were antagonized in treated ZEBOV- and MARV-infected cells, while in contrast, REBOV infection resulted in a significant increase in ISG expression. Analysis of STAT1 and -2 phosphorylation following IFN treatment showed a significant reduction of STAT phosphorylation for MARV but not for ZEBOV and REBOV, indicating that different mechanisms might be involved in antagonizing IFN signaling pathways by the different filovirus species. Taken together, these studies showed a correlation between antagonism of type I IFN responses and filovirus virulence.
Identification of the Nucleocapsid, Tegument, and Envelope Proteins of the Shrimp White Spot Syndrome Virus Virion
Authors: Tsai Jyh-Ming , Wang Han-Ching , Leu Jiann-Horng , Wang Andrew H.-J. , Zhuang Ying , Walker Peter J. , Kou Guang-Hsiung , Lo Chu-Fang 
Published: February 2006

ABSTRACT
The protein components of the white spot syndrome virus (WSSV) virion have been well established by proteomic methods, and at least 39 structural proteins are currently known. However, several details of the virus structure and assembly remain controversial, including the role of one of the major structural proteins, VP26. In this study, Triton X-100 was used in combination with various concentrations of NaCl to separate intact WSSV virions into distinct fractions such that each fraction contained envelope and tegument proteins, tegument and nucleocapsid proteins, or nucleocapsid proteins only. From the protein profiles and Western blotting results, VP26, VP36A, VP39A, and VP95 were all identified as tegument proteins distinct from the envelope proteins (VP19, VP28, VP31, VP36B, VP38A, VP51B, VP53A) and nucleocapsid proteins (VP664, VP51C, VP60B, VP15). We also found that VP15 dissociated from the nucleocapsid at high salt concentrations, even though DNA was still present. These results were confirmed by CsCl isopycnic centrifugation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry, by a trypsin sensitivity assay, and by an immunogold assay. Finally, we propose an assembly process for the WSSV virion.
Identification and Characterization of the Orf49 Protein of Kaposi's Sarcoma-Associated Herpesvirus
Authors: González Carlos M. , Wong Emily L. , Bowser Brian S. , Hong Gregory K. , Kenney Shannon , Damania Blossom 
Published: February 2006

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Kaposi's sarcoma is the most common neoplasm among human immunodeficiency virus-positive individuals. Like other herpesviruses, KSHV is able to establish a predominantly latent, life-long infection in its host. The KSHV lytic cycle can be triggered by a number of stimuli that induce the expression of the key lytic switch protein, the replication and transcription activator (RTA) encoded by Orf50. The expression of Rta is necessary and sufficient to trigger the full lytic program resulting in the ordered expression of viral proteins, release of viral progeny, and host cell death. We have characterized an unknown open reading frame, Orf49, which lies adjacent and in the opposite orientation to Orf50. Orf49 is expressed during the KSHV lytic cycle and shows early transcription kinetics. We have mapped the 5′ and 3′ ends of the unspliced Orf49 transcript, which encodes a 30-kDa protein that is localized to both the nucleus and the cytoplasm. Interestingly, we found that Orf49 was able to cooperate with Rta to activate several KSHV lytic promoters containing AP-1 sites. The Orf49-encoded protein was also able to induce transcriptional activation through c-Jun but not the ATF1, ATF2, or CREB transcription factor. We found that Orf49 could induce phosphorylation and activation of the transcription factor c-Jun, the Jun N-terminal kinase (JNK), and p38. Our data suggest that Orf49 functions to activate the JNK and p38 pathways during the KSHV lytic cycle.
Perforin Expression in the Gastrointestinal Mucosa Is Limited to Acute Simian Immunodeficiency Virus Infection
Authors: Quigley Máire F. , Abel Kristina , Zuber Bartek , Miller Christopher J. , Sandberg Johan K. , Shacklett Barbara L. 
Published: February 2006

ABSTRACT
Perforin-mediated cytotoxicity is a major effector function of virus-specific CD8 T cells. We have investigated the expression of perforin in the gut, an important site of simian immunodeficiency virus (SIV) pathogenesis, during experimental SIV infection of rhesus macaques. We observed significant increases in perforin protein and mRNA expression levels in the colons of SIV-infected macaques as early as 21 days after infection. However, during chronic infection, despite ongoing viral replication, perforin expression returned to levels similar to those detected in SIV-naïve animals. These findings demonstrate the presence of a robust perforin-positive response in gastrointestinal CD8 T cells during acute, but not chronic, SIV infection.
Rhesus Rhadinovirus R15 Encodes a Functional Homologue of Human CD200
Authors: Langlais Carly L. , Jones John M. , Estep Ryan D. , Wong Scott W. 
Published: February 2006

ABSTRACT
A viral CD200 homologue (vCD200) encoded by open reading frame R15 of rhesus rhadinovirus (RRV), a gammaherpesvirus closely related to human herpesvirus 8 (HHV-8), is described here. RRV vCD200 shares 30% and 28% amino acid identity with human CD200 (huCD200) and HHV-8 vCD200, respectively. In vitro analysis indicated that an Fc fusion (vCD200-Fc) is expressed as a glycoprotein with a core molecular mass of 53 kDa. Utilizing monoclonal antibodies raised against vCD200-Fc, vCD200 expression was detected on the surfaces of and within supernatants from infected fibroblasts. Furthermore, in vitro assays demonstrated that vCD200-Fc treatment of monocyte-derived macrophages reduces tumor necrosis factor transcript and protein levels, implying that RRV encodes a functional vCD200.
Identification of Mutations Causing Temperature-Sensitive Defects in Semliki Forest Virus RNA Synthesis
Authors: Lulla Valeria , Merits Andres , Sarin Peter , Kääriäinen Leevi , Keränen Sirkka , Ahola Tero 
Published: February 2006

ABSTRACT
We have sequenced the nonstructural protein coding region of Semliki Forest virus temperature-sensitive (ts) mutant strains ts1, ts6, ts9, ts10, ts11, ts13, and ts14. In each case, the individual amino acid changes uncovered were transferred to the prototype strain background and thereby identified as the underlying cause of the altered RNA synthesis phenotype. All mutations mapping to the protease domain of nonstructural protein nsP2 caused defects in nonstructural polyprotein processing and subgenomic RNA synthesis, and all mutations in the helicase domain of nsP2 affected subgenomic RNA production. These types of defects were not associated with mutations in other nonstructural proteins.
c-mycAmplifications in primary breast carcinomas and their local recurrences
Authors: Aulmann S , Adler N , Rom J , Helmchen B , Schirmacher P , Sinn H P 
Published: February 2006

Objective:To evaluate the role of c-myconcogene amplifications in the progression of invasive breast carcinomas.Methods:c-mycgene copy number was evaluated in a series of 49 primary breast carcinomas and the corresponding local recurrences using fluorescence in situ hybridisation.Results:11 of the primary carcinomas (22%) harboured c-mycamplifications; these tumours typically were hormone receptor negative and occurred in younger patients (43v53 years). At the time of relapse, six additional tumours had acquired a c-mycamplification. The mean recurrence-free survival was 24 months; c-mycamplified tumours relapsed significantly earlier than carcinomas without amplification (18v27 months). Univariate analysis showed a worse overall survival in these patients.Conclusions:While c-mycamplifications can be observed in early stage breast cancer, especially in younger patients, they often occur later in tumour development and appear to be associated with disease progression.
The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma
Authors: Cserni G , Bianchi S , Vezzosi V , Peterse H , Sapino A , Arisio R , Reiner-Concin A , Regitnig P , Bellocq J-P , Marin C , Bori R , Penuela J M , Córdoba Iturriagagoitia A 
Published: February 2006

Background:Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients.Objective:To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma.Methods:The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis.Results:189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general.Conclusions:IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.
Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways
Authors: Schmitz K J , Callies R , Wohlschlaeger J , Kimmig R , Otterbach F , Bohr J , Lee H-S , Takeda A , Schmid K W , Baba H A 
Published: February 2006

Background and aim:The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways—namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu—is assessed in a series of 113 node-negative breast cancers.Results:COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis.Conclusions:The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed—COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.
Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort
Authors: Kouvonen A , Kivimäki M , Elovainio M , Pentti J , Linna A , Virtanen M , Vahtera J 
Published: February 2006

Objectives:To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle.Methods:Cross sectional data from the ongoing Finnish Public Sector Study related to 30 433 women and 7718 men aged 17–64 were used (n = 35 918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as <2.00 metabolic equivalent task (MET) hours/day. Logistic regression with generalised estimating equations was used as an analysis method to include both individual and work unit level predictors in the models. Adjustments were made for age, marital status, occupational status, job contract, smoking, and heavy drinking.Results:Twenty five per cent of women and 27% of men had a sedentary lifestyle. High individual level ERI was associated with a higher likelihood of sedentary lifestyle both among women (odds ratio (OR) = 1.08, 95% CI 1.01 to 1.16) and men (OR = 1.17, 95% CI 1.02 to 1.33). These associations were not explained by relevant confounders and they were also independent of work unit level job strain measured as a ratio of job demands and control.Conclusions:A mismatch between high occupational effort spent and low reward received in turn seems to be associated with an increased risk of sedentary lifestyle, although this association is relatively weak.
Healthcare use before and after a workplace injury in British Columbia, Canada
Authors: Brown J A , McDonough P , Mustard C A , Shannon H S 
Published: February 2006

Objectives:There is growing evidence that occupational injuries influence workers’ emotional and physical wellbeing, extending healthcare use beyond what is covered by the Workers’ Compensation Board (WCB).Methods:The authors used an administrative database that links individual publicly funded healthcare and WCB data for the population of British Columbia (BC), Canada. They examined change in service use, relative to one year before the injury, for workers who required time off for their injuries (lost time = LT) and compared them to other injured workers (no lost time = NLT) and individuals in the population who were not injured (non-injured = NI).Results:LT workers increased physician visits (22%), hospital days (50%), and mental healthcare use (43% physician visits; and 70% hospital days) five years after the injury, relative to the year before the injury, at a higher rate than the NI group. For the NLT workers, the level of increased use following the injury was between that of these two groups. These patterns persisted when adjusting for registration in the BC Medical Service Plan (MSP) and several workplace characteristics.Conclusions:Although the WCB system is the primary mechanism for processing claims and providing information about workplace injury, it is clear that the consequences of workplace injury extend beyond what is covered by the WCB into the publicly funded healthcare system.