bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Toll-Like Receptor 3-Mediated Antiviral Response Is Important for Protection against Poliovirus Infection in Poliovirus Receptor Transgenic Mice
Authors: Abe Yuko , Fujii Ken , Nagata Noriyo , Takeuchi Osamu , Akira Shizuo , Oshiumi Hiroyuki , Matsumoto Misako , Seya Tsukasa , Koike Satoshi 
Published: November 2011

ABSTRACT

RIG-I-like receptors and Toll-like receptors (TLRs) play important roles in the recognition of viral infections. However, how these molecules contribute to the defense against poliovirus (PV) infection remains unclear. We characterized the roles of these sensors in PV infection in transgenic mice expressing the PV receptor. We observed that alpha/beta interferon (IFN-α/β) production in response to PV infection occurred in an MDA5-dependent but RIG-I-independent manner in primary cultured kidney cells
in vitro
. These results suggest that, similar to the RNA of other picornaviruses, PV RNA is recognized by MDA5. However, serum IFN-α levels, the viral load in nonneural tissues, and mortality rates did not differ significantly between MDA5-deficient mice and wild-type mice. In contrast, we observed that serum IFN production was abrogated and that the viral load in nonneural tissues and mortality rates were both markedly higher in TIR domain-containing adaptor-inducing IFN-β (TRIF)-deficient and TLR3-deficient mice than in wild-type mice. The mortality rate of MyD88-deficient mice was slightly higher than that of wild-type mice. These results suggest that multiple pathways are involved in the antiviral response in mice and that the TLR3-TRIF-mediated signaling pathway plays an essential role in the antiviral response against PV infection.
Conserved Glycine 33 Residue in Flexible Domain I of Hepatitis C Virus Core Protein Is Critical for Virus Infectivity
Authors: Angus Allan G. N. , Loquet Antoine , Stack Séamus J. , Dalrymple David , Gatherer Derek , Penin François , Patel Arvind H. 
Published: November 2011

ABSTRACT

Hepatitis C virus core protein forms the viral nucleocapsid and plays a critical role in the formation of infectious particles. In this study, we demonstrate that the highly conserved residue G33, located within domain 1 of the core protein, is important for the production of cell culture-infectious virus (HCVcc). Alanine substitution at this position in the JFH1 genome did not alter viral RNA replication but reduced infectivity by ∼2 logs. Virus production by this core mutant could be rescued by compensatory mutations located immediately upstream and downstream of the original G33A mutation. The examination of the helix-loop-helix motif observed in the core protein structure (residues 15 to 41; Protein Data Bank entry
1CWX
) indicated that the residues G33 and F24 are in close contact with each other, and that the G33A mutation induces a steric clash with F24. Molecular simulations revealed that the compensatory mutations increase the helix-loop-helix flexibility, allowing rescue of the core active conformation required for efficient virus production. Taken together, these data highlight the plasticity of core domain 1 conformation and illustrate the relationship between its structural tolerance to mutations and virus infectivity.
Combination of PB2 271A and SR Polymorphism at Positions 590/591 Is Critical for Viral Replication and Virulence of Swine Influenza Virus in Cultured Cells and
In Vivo
Authors: Liu Qinfang , Qiao Chuanling , Marjuki Henju , Bawa Bhupinder , Ma Jingqun , Guillossou Stephane , Webby Richard J. , Richt Jürgen A. , Ma Wenjun 
Published: November 2011

ABSTRACT
Triple reassortant swine influenza viruses (SIVs) and 2009 pandemic H1N1 (pH1N1) virus contain an avian-origin PB2 with 271A, 590S, 591R, and 627E. To evaluate the role of PB2 271A, 590S, and 591R in the replication and virulence of SIV, single (1930-TX98-PB2-271T)-, double (1930-TX98-PB2-590A591A)-, and triple (1930-TX98-PB2-271T590A591A)-mutated viruses were generated in the background of the H1N1 A/swine/Iowa/15/30 (1930) virus with an avian-origin PB2 from the triple-reassortant A/swine/Texas/4199-2/98 (TX98) virus, called the parental 1930-TX98-PB2. Compared to parental virus and single- and double-mutated viruses, the triple-mutated virus replicated less efficiently in cell cultures and was attenuated in mice. These results suggest that a combination of 271A with the 590/591 SR polymorphism is critical for pH1N1 and triple-reassortant SIVs for efficient replication and adaptation in mammals.
Genetic Inactivation of COPI Coatomer Separately Inhibits Vesicular Stomatitis Virus Entry and Gene Expression
Authors: Cureton David K. , Burdeinick-Kerr Rebeca , Whelan Sean P. J. 
Published: November 2011

ABSTRACT
Viruses coopt cellular membrane transport to invade cells, establish intracellular sites of replication, and release progeny virions. Recent genome-wide RNA interference (RNAi) screens revealed that genetically divergent viruses require biosynthetic membrane transport by the COPI coatomer complex for efficient replication. Here we found that disrupting COPI function by RNAi inhibited an early stage of vesicular stomatitis virus (VSV) replication. To dissect which replication stage(s) was affected by coatomer inactivation, we used visual and biochemical assays to independently measure the efficiency of viral entry and gene expression in hamster (ldlF) cells depleted of the temperature-sensitive ε-COP subunit. We show that ε-COP depletion for 12 h caused a primary block to virus internalization and a secondary defect in viral gene expression. Using brefeldin A (BFA), a chemical inhibitor of COPI function, we demonstrate that short-term (1-h) BFA treatments inhibit VSV gene expression, while only long-term (12-h) treatments block virus entry. We conclude that prolonged coatomer inactivation perturbs cellular endocytic transport and thereby indirectly impairs VSV entry. Our results offer an explanation of why COPI coatomer is frequently identified in screens for cellular factors that support cell invasion by microbial pathogens.
Complex Dynamic Development of Poliovirus Membranous Replication Complexes
Authors: Belov George A. , Nair Vinod , Hansen Bryan T. , Hoyt Forrest H. , Fischer Elizabeth R. , Ehrenfeld Ellie 
Published: November 2011

ABSTRACT

Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from
cis
-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses.
Recent Mumps Outbreaks in Vaccinated Populations: No Evidence of Immune Escape
Authors: Rubin Steven A. , Link Malen A. , Sauder Christian J. , Zhang Cheryl , Ngo Laurie , Rima Bert K. , Duprex W. Paul 
Published: November 2011

ABSTRACTRecently, numerous large-scale mumps outbreaks have occurred in vaccinated populations. Clinical isolates sequenced from these outbreaks have invariably been of genotypes distinct from those of vaccine viruses, raising concern that certain mumps virus strains may escape vaccine-induced immunity. To investigate this concern, sera obtained from children 6 weeks after receipt of measles, mumps, and rubella (MMR) vaccine were tested for the ability to neutralize a carefully selected group of genetically diverse mumps virus strains. Although the geometric mean neutralizing antibody titer of the sera was lower against some virus strains than others, all viruses were readily neutralized, arguing against immune escape.
Epigenetic Changes Mediated by MicroRNA miR29 Activate Cyclooxygenase 2 and Lambda-1 Interferon Production during Viral Infection
Authors: Fang Jiali , Hao Qian , Liu Li , Li Yongkui , Wu Jianguo , Huo Xixiang , Zhu Ying 
Published: November 2011

ABSTRACTLambda-1 interferon (IFN-λ1) and cyclooxygenase-2 (COX-2) were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-λ1 and COX2 are activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-λ1 and COX2-derived prostaglandin E2 (PGE2) was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-λ1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells but enhanced by overexpression of COX2, indicating that the production of IFN-λ1 is COX2 dependent. COX2 was able to increase IFN-λ1 expression by promoting NF-κB binding to the enhancer in the IFN-λ1 promoter. We found that epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase 3a (DNMT3a) and DNMT3b, but not that of DNMT1, was downregulated following influenza A virus infection in both A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA miR29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection.
Impact of Vaccination on Cytotoxic T Lymphocyte Immunodominance and Cooperation against Simian Immunodeficiency Virus Replication in Rhesus Macaques
Authors: Ishii Hiroshi , Kawada Miki , Tsukamoto Tetsuo , Yamamoto Hiroyuki , Matsuoka Saori , Shiino Teiichiro , Takeda Akiko , Inoue Makoto , Iida Akihiro , Hara Hiroto , Shu Tsugumine , Hasegawa Mamoru , Naruse Taeko K. , Kimura Akinori , Takiguchi Masafumi , Matano Tetsuro 
Published: November 2011

ABSTRACT

Cytotoxic T lymphocyte (CTL) responses play a central role in viral suppression in human immunodeficiency virus (HIV) infections. Prophylactic vaccination resulting in effective CTL responses after viral exposure would contribute to HIV control. It is important to know how CTL memory induction by vaccination affects postexposure CTL responses. We previously showed vaccine-based control of a simian immunodeficiency virus (SIV) challenge in a group of Burmese rhesus macaques sharing a major histocompatibility complex class I haplotype. Gag
206-216
and Gag
241-249
epitope-specific CTL responses were responsible for this control. In the present study, we show the impact of individual epitope-specific CTL induction by prophylactic vaccination on postexposure CTL responses. In the acute phase after SIV challenge, dominant Gag
206-216
-specific CTL responses with delayed, naive-derived Gag
241-249
-specific CTL induction were observed in Gag
206-216
epitope-vaccinated animals with prophylactic induction of single Gag
206-216
epitope-specific CTL memory, and vice versa in Gag
241-249
epitope-vaccinated animals with single Gag
241-249
epitope-specific CTL induction. Animals with Gag
206-216
-specific CTL induction by vaccination selected for a Gag
206-216
-specific CTL escape mutation by week 5 and showed significantly less decline of plasma viral loads from week 3 to week 5 than in Gag
241-249
epitope-vaccinated animals without escape mutations. Our results present evidence indicating significant influence of prophylactic vaccination on postexposure CTL immunodominance and cooperation of vaccine antigen-specific and non-vaccine antigen-specific CTL responses, which affects virus control. These findings provide great insights into antigen design for CTL-inducing AIDS vaccines.
Human Pulmonary Microvascular Endothelial Cells Support Productive Replication of Highly Pathogenic Avian Influenza Viruses: Possible Involvement in the Pathogenesis of Human H5N1 Virus Infection
Authors: Zeng Hui , Pappas Claudia , Belser Jessica A. , Houser Katherine V. , Zhong Weiming , Wadford Debra A. , Stevens Troy , Balczon Ron , Katz Jacqueline M. , Tumpey Terrence M. 
Published: November 2011

ABSTRACT
Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (α2-3-linked) receptors were more abundant than human-like (α2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses.
Interspecific and intraspecific variations in water storage in epiphytic old forest foliose lichens
Authors: Gauslaa Yngvar , Coxson Darwyn 
Published: November 2011

Cyanolichens ( Lobaria hallii , Lobaria retigera , Lobaria scrobiculata , Pseudocyphellaria anomala ) and cephalodial ( Lobaria pulmonaria ) and noncephalodial ( Platismatia glauca ) chlorolichens were sampled in dry open, mesic open, and mesic closed forests in central British Columbia. Specific thallus mass (STM), water-holding capacity (WHC), percent water content at saturation, and thickness of upper cortex, photobiont layer, and medulla plus lower cortex were measured. Whereas STM did not differ much between cyanolichens (9.8 ± 0.1 mg dry mass·cm–2) and chlorolichens (8.0 ± 0.1 mg dry mass·cm–2), cyanolichens had a WHC (20.3 ± 0.2 mg H2O·cm–2) that was nearly twice that of the chlorolichens (10.8 ± 0.2 mg H2O·cm–2). STM and WHC increased with light exposure at the studied sites, presumably as an acclimation to higher evaporation demands. Within species, WHC was strongly coupled to STM and increased substantially faster with STM in cyanolichens, compensating their inability to use humid air to restore photosynthesis. The photobiont layer was two times thicker in cyanolichens, whereas the thickest layer (the hydrophobic medulla) did not differ between cyanolichens and chlorolichens. Most interspecific variation (88.3%) in WHC could be accounted for in a multiple regression model where STM and photobiont to total thickness ratio were the most important independent variables. Photobionts thus play significant roles in the water economy of lichens.
The Importance of Doing Trials Right While Doing the Right Trials
Authors: Dilts David M. , Cheng Steven K. 
Published: November 2011

Abstract
Effort is being expended in investigating efficiency measures (i.e., doing trials right) through achievement of accrual and endpoint goals for clinical trials. It is time to assess the impact of such trials on meeting the critical needs of cancer patients by establishing effectiveness measures (i.e., doing the right trials). Clin Cancer Res; 18(1); 3–5. ©2011 AACR.
Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis
Authors: Buttari Brigitta , Petrone Linda , Straface Elisabetta , Gambardella Lucrezia , Pietraforte Donatella , Genuini Igino , Capoano Raffaele , Salvati Bruno , Malorni Walter , Riganò Rachele , Profumo Elisabetta 
Published: November 2011

SummaryOxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis.
Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients
Authors: Lee Keun-Wook , Bang Soo-Mee , Kim Sujung , Lee Jeong-Ok , Kim Yu , Kim Jee Hyun , Park Young , Kim Duck-Woo , Kang Sung-Bum , Kim Jae-Sung , Oh Doyeun , Lee Jong , Choi Seyoun 
Published: November 2011

SummaryThis study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.
Comparative natural aging of thermoplastic elastomeric and silicon rubber insulators in Pakistan
Authors: Amin Salman 
Published: November 2011

Polymeric insulators have gained popularity since the last 30 years throughout the world. The main concern about them is variation in their performance with varying environments. Investigation of their performance by natural and artificial aging experiments is under the way by many researchers all over the world. The natural aging is usually short-term experiment ranging from few days to few years. The artificial aging is usually long-term investigation in lab that simulates the real service environment. However, first of all to develop the artificial aging schemes, natural aging to some extent is necessary. This article presents a part of research on polymeric insulators ongoing at the University of Engineering & Technology, Taxila, in which 2 different kinds of polymeric insulators were naturally aged in a period of 1 year. The materials used were the thermoplastic elastomeric and thermoset silicone rubber (SiR) insulators. They were aged in outdoor environment of Hattar, which is a heavily polluted industrial area of Pakistan. The actual 11 kV full-scale insulators were installed in open environment at a height of about 30 m. The samples were cut from the insulators and analyzed using visual observation, hydrophobicity classification, leakage current and Fourier transform infrared spectroscopy and scanning electron microscopy. The main aims of this aging were estimation of the useful life of these insulators under the environment studied and development of basis for multistress lab aging cycles. The results were also used to compare the performance of these two materials with each other.