bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effects of Vaccination against Porcine Circovirus Type 2 (PCV2) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in a PCV2-PRRSV Challenge Model
Authors: Park Changhoon , Oh Yeonsu , Seo Hwi Won , Han Kiwon , Chae Chanhee 
Published: January 2013

ABSTRACTThe objective of the present study was to determine the effects of porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) vaccinations in an experimental PCV2-PRRSV challenge model, based on virological (viremia), immunological (neutralizing antibodies [NAs], gamma interferon-secreting cells [IFN-γ-SCs], and CD4+CD8+double-positive cells), and pathological (lesions and antigens in lymph nodes and lungs) evaluations. A total of 72 pigs were randomly divided into 9 groups (8 pigs per group): 5 vaccinated and challenged groups, 3 nonvaccinated and challenged groups, and a negative-control group. Vaccination against PCV2 induced immunological responses (NAs and PCV2-specific IFN-γ-SCs) and reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PCV2 did not affect the PRRSV immunological responses (NAs and PRRSV-specific IFN-γ-SCs), PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. Vaccination against PRRSV did not induce immunological responses (PRRSV-specific IFN-γ-SCs) or reduce PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. In addition, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. In summary, vaccination against PCV2 reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. Therefore, the PCV2 vaccine decreased the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs. In contrast, the PRRSV vaccine alone did not decrease the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs.
Pathogen Chip for Respiratory Tract Infections
Authors: Simões Eric A. F. , Patel Champa , Sung Wing-Kin , Lee Charlie W. H. , Loh Kuan Hon , Lucero Marilla , Nohynek Hanna , Nai Geraldine , Thien Pei Ling , Koh Chee Wee , Chan Yang Sun , Ma Jianmin , Maurer-Stroh Sebastian , Carosone-Link Phyllis , Hibberd Martin L. , Wong Christopher W. ,   ARIVAC Consortium
Published: January 2013

ABSTRACT
Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods—EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods.
Hepatitis B and E Co-Primary Infections in an HIV-1-Infected Patient
Authors: Bouamra Yanis , Benali Souad , Tissot-Dupont Hervé , Tamalet Catherine , Colson Philippe 
Published: January 2013

ABSTRACTWe report an autochthonous hepatitis E virus (HEV)-hepatitis B virus co-primary infection in a 41-year-old man having sex with men and infected with human immunodeficiency virus (HIV). This case prompts testing for HEV in HIV-infected patients with acute hepatitis even if primary infection with another hepatitis virus is diagnosed.
Klebsiella pneumoniae K1 Liver Abscess and Septic Endophthalmitis in a U.S. Resident
Authors: Sachdev Darpun D. , Yin Michael T. , Horowitz Jason D. , Mukkamala Sri Krishna , Lee Song Eun , Ratner Adam J. 
Published: January 2013

ABSTRACT

Klebsiella pneumoniae
K1 is a major agent of hepatic abscess with metastatic disease in East Asia, with sporadic reports originating elsewhere. We report a case of abscess complicated by septic endophthalmitis caused by a
wzyA
KpK1-positive
Klebsiella
strain in a U.S. resident, raising concern for global emergence.
Filoviruses Utilize Glycosaminoglycans for Their Attachment to Target Cells
Authors: Salvador Beatriz , Sexton Nicole R. , Carrion Ricardo , Nunneley Jerritt , Patterson Jean L. , Steffen Imke , Lu Kai , Muench Marcus O. , Lembo David , Simmons Graham 
Published: January 2013

ABSTRACT
Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells.
The Absence of M1 Leads to Increased Establishment of Murine Gammaherpesvirus 68 Latency in IgD-Negative B Cells
Authors: Krug Laurie T. , Evans Andrew G. , Gargano Lisa M. , Paden Clinton R. , Speck Samuel H. 
Published: January 2013

ABSTRACTThe secreted M1 protein of murine gammaherpesvirus 68 (MHV68) promotes effector Vβ4+CD8+T cell expansion to impact virus control and immune-mediated pathologies in C57BL/6 mice, but not BALB/c mice. We report a striking increase in the number of genome-positive, IgD−B cells during chronic infection of both mouse strains. This suggests a novel role for M1 in influencing long-term maintenance in a major latency reservoir irrespective of the degree of Vβ4+CD8+T cell expansion.
Toll-Like Receptor Expression and Induction of Type I and Type III Interferons in Primary Airway Epithelial Cells
Authors: Ioannidis Ioannis , Ye Fang , McNally Beth , Willette Meredith , Flaño Emilio 
Published: January 2013

ABSTRACTInterferons (IFNs) are a critical component of the first line of antiviral defense. The activation of Toll-like receptors (TLRs) expressed by dendritic cells triggers different signaling cascades that result in the production of large amounts of IFNs. However, the functional consequences of TLR activation and differential IFN production in specific cell populations other than antigen-presenting cells have not yet been fully elucidated. In this study, we investigated TLR expression and polarization in airway epithelial cells (AECs) and the consequences of TLR agonist stimulation for the production of type I (IFN-α/β) and type III (IFN-λ) IFNs. Our results show that the pattern of expression and polarization of all TLRs in primary AEC cultures mirrors that of the human airwaysex vivoand is receptor specific. The antiviral TLRs (TLR3, TLR7, and TLR9) are mostly expressed on the apical cell surfaces of epithelial cells in the human trachea and in primary polarized AECs. Type III IFN is the predominant IFN produced by the airway epithelium, and TLR3 is the only TLR that mediates IFN production by AECs, while all TLR agonists tested are capable of inducing AEC activation and interleukin-8 production. In response to influenza virus infection, AECs can produce IFN-λ in an IFNAR- and STAT1-independent manner. Our results emphasize the importance of using primary well-differentiated AECs to study TLR and antiviral responses and provide further insight into the regulation of IFN production during the antiviral response of the lung epithelium.
Innate Immune Defense Defines Susceptibility of Sarcoma Cells to Measles Vaccine Virus-Based Oncolysis
Authors: Berchtold Susanne , Lampe Johanna , Weiland Timo , Smirnow Irina , Schleicher Sabine , Handgretinger Rupert , Kopp Hans-Georg , Reiser Jeanette , Stubenrauch Frank , Mayer Nora , Malek Nisar P. , Bitzer Michael , Lauer Ulrich M. 
Published: January 2013

ABSTRACT
The oncolytic potential of measles vaccine virus (MeV) has been demonstrated in several tumor entities. Here, we investigated the susceptibility of eight sarcoma cell lines to MeV-mediated oncolysis and found five to be susceptible, whereas three proved to be resistant. In the MeV-resistant cell lines, we often observed an inhibition of viral replication along with a strong upregulation of the intracellular virus-sensing molecule RIG-I and of the interferon (IFN)-stimulated gene IFIT1. Not only expression of IFIT1 but also phosphorylation of IFN-stimulated Stat1 took place rapidly and were found to be persistent over time. In contrast, susceptible cell lines showed a much weaker, delayed, or completely missing expression of IFIT1 as well as a delayed or only transient phosphorylation of Stat1, whereas exogenic stimulation with beta interferon (IFN-β) resulted in a comparable profound activation of Stat1 and expression of IFIT1 in all cell lines. Pretreatment with IFN-β rendered three of the susceptible cell lines more resistant to MeV-mediated oncolysis. These data suggest that differences in the innate immune defense often account for different degrees of susceptibility of sarcoma cell lines to MeV-mediated oncolysis. From a therapeutic perspective, we were able to overcome resistance to MeV by increasing the multiplicity of infection (MOI) and by addition of the prodrug 5-fluorocytosine (FC), thereby exploiting the suicide gene function of virotherapeutic vector MeV-SCD armed with the SCD fusion protein, which consists of yeast cytosine deaminase and yeast uracil phosphoribosyltransferase.
Henipavirus Pathogenesis in Human Respiratory Epithelial Cells
Authors: Escaffre Olivier , Borisevich Viktoriya , Carmical J. Russ , Prusak Deborah , Prescott Joseph , Feldmann Heinz , Rockx Barry 
Published: January 2013

ABSTRACT

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and
in vivo
studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection.
Inflammasome Adaptor Protein Apoptosis-Associated Speck-Like Protein Containing CARD (ASC) Is Critical for the Immune Response and Survival in West Nile Virus Encephalitis
Authors: Kumar Mukesh , Roe Kelsey , Orillo Beverly , Muruve Daniel A. , Nerurkar Vivek R. , Gale Michael , Verma Saguna 
Published: January 2013

ABSTRACT

West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. The WNV-induced innate immune response, including production of antiviral cytokines, is critical for controlling virus infection. The adaptor protein ASC mediates a critical step in innate immune signaling by bridging the interaction between the pathogen recognition receptors and caspase 1 in inflammasome complexes, but its role in WNV immunopathogenesis is not defined. Here, we demonstrate that ASC is essential for interleukin-1β (IL-1β) production and development of effective host immunity against WNV. ASC-deficient mice exhibited increased susceptibility to WNV infection, and reduced survival was associated with enhanced virus replication in the peripheral tissues and central nervous system (CNS). Infection of cultured bone marrow-derived dendritic cells showed that ASC was essential for the activation of caspase 1, a key component of inflammasome assembly. ASC
−/−
mice exhibited attenuated levels of proinflammatory cytokines in the serum. Intriguingly, infected ASC
−/−
mice also displayed reduced levels of alpha interferon (IFN-α) and IgM in the serum, indicating the overall protective role of ASC in restricting WNV infection. However, brains from ASC
−/−
mice displayed unrestrained inflammation, including elevated levels of proinflammatory cytokines and chemokines, such as IFN-γ, CCL2, and CCL5, which correlated with more pronounced activation of the astrocytes, enhanced infiltration of peripheral immune cells in the CNS, and increased neuronal cell death. Collectively, our data provide new insights into the role of ASC as an essential modulator of inflammasome-dependent and -independent immune responses to effectively control WNV infection.
A Virally Encoded Small Peptide Regulates RTA Stability and Facilitates Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication
Authors: Jaber Tareq , Yuan Yan 
Published: January 2013

ABSTRACT
In both mammalian and viral genomes, a large proportion of sequences are transcribed and annotated as noncoding RNAs. A polyadenylated RNA of 3.0 kb (T3.0) is transcribed from the opposite strand of the open reading frame 50 (ORF50) DNA template in the genome of Kaposi's sarcoma-associated herpesvirus (KSHV) and has been annotated previously as a noncoding RNA. ORF50 encodes the replication and transcription activator (RTA), which controls the switch of the virus between the latent and lytic phases of the life cycle. Here we show that T3.0 encodes a small peptide of 48 amino acids (designated viral small peptide 1 [vSP-1]). vSP-1 interacts with RTA at the protein abundance regulatory signal (PARS) motifs, and the association prevents RTA from being subjected to degradation through the ubiquitin-proteasome pathway. As a consequence, vSP-1 facilitates KSHV gene expression and lytic replication. This finding reveals a novel mechanism of gene regulation in the viral life cycle.
T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+Donors
Authors: Jelčić Ilijas , Aly Lilian , Binder Thomas M. C. , Jelčić Ivan , Bofill-Mas Sílvia , Planas Raquel , Demina Victoria , Eiermann Thomas H. , Weber Thomas , Girones Rosina , Sospedra Mireia , Martin Roland 
Published: January 2013

ABSTRACTJC polyomavirus (JCV) infection is highly prevalent and usually kept in a persistent state without clinical signs and symptoms. It is only during immunocompromise and especially impaired CD4+T cell function in the brain, as seen in AIDS patients or natalizumab-treated multiple sclerosis patients, that JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4+T cells likely play an important role in controlling JCV infection, we here describe the T cell response to JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames. We identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. We observed positive JCV-specific T cell responses in 28.6% to 77.6%, humoral immune response in 42.6% to 89.4%, and urinary viral shedding in 36.4% to 45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01+, DRB1*07+, DRB1*11+, DRB1*13+, DRB1*15+, and DRB1*03+individuals. We show for the first time that JCV-specific T cell responses may be directed not only against JCV VP1 and large T antigen but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01+individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV.
Adenovirus L-E1A Activates Transcription through Mediator Complex-Dependent Recruitment of the Super Elongation Complex
Authors: Vijayalingam S. , Chinnadurai G. 
Published: January 2013

ABSTRACT

The adenovirus large E1A (L-E1A) protein is a prototypical transcriptional activator, and it functions through the action of a conserved transcriptional activation domain, CR3. CR3 interacts with a mediator subunit, MED23, that has been linked to the transcriptional activity of CR3. Our unbiased proteomic analysis revealed that human adenovirus 5 (HAdv5) L-E1A was associated with many mediator subunits. In MED23-depleted cells and in
Med23
knockout (KO) cells, L-E1A was deficient in association with other mediator subunits, suggesting that MED23 links CR3 with the mediator complex. Short interfering RNA (siRNA)-mediated depletion of several mediator subunits suggested differential effects of various subunits on transcriptional activation of HAdv5 early genes. In addition to MED23, mediator subunits such as MED14 and MED26 were also essential for the transcription of HAdv5 early genes. The L-E1A proteome contained MED26-associated super elongation complex. The catalytic component of the elongation complex, CDK9, was important for the transcriptional activity of L-E1A and HAdv5 replication. Our results suggest that L-E1A-mediated transcriptional activation involves a transcriptional elongation step, like HIV Tat, and constitutes a therapeutic target for inhibition of HAdv replication.
Assessment of hypovolaemic shock at scene: is the PHTLS classification of hypovolaemic shock really valid?
Authors: Mutschler Manuel , Nienaber Ulrike , Münzberg Matthias , Fabian Tobias , Paffrath Thomas , Wölfl Christoph , Bouillon Bertil , Maegele Marc 
Published: January 2013

ObjectiveValidation of the classification of hypovolaemic shock suggested by the prehospital trauma life support (PHTLS) in its sixth student course manual.MethodsAdults, entered into the TraumaRegister DGU®database between 2002 and 2011, were classified into reference ranges for heart rate (HR), systolic blood pressure (SBP) and Glasgow coma scale (GCS) according to the PHTLS classification of hypovolaemic shock. First, patients were grouped by a combination of all three parameters (HR, SBP and GCS) as suggested by PHTLS. Second, patients were classified by only one parameter (HR, SBP or GCS) according to PHTLS and alterations in the remaining two parameters were assessed. Furthermore, subgroup analysis for trauma mechanism and traumatic brain injury (TBI) were performed.ResultsOut of 46 689 patients, only 12 432 (26.5%) could be adequately classified according to PHTLS if a combination of all three criteria was assessed. In TBI patients, only 12.2% could be classified adequately, whereas trauma mechanism had no significant influence. When patients were grouped by HR, there was only a slight reduction in SBP. When grouped by SBP, GCS dropped from 14 to 8, while no significant tachycardia was observed in any group. In patients with a GCS less than 12, HR was unaltered whereas SBP was slightly reduced to 114 (±42) mm Hg. On average, GCS in TBI patients was lower within all shock groups. In penetrating trauma patients, changes in HR and SBP were more distinct, but still less than predicted by PHTLS.ConclusionsThe PHTLS classification of hypovolaemic shock displays substantial deficits in adequately risk-stratifying trauma patients.
Cisplatin Hypersensitivity of Testicular Germ Cell Tumors Is Determined by High Constitutive Noxa Levels Mediated by Oct-4
Authors: Gutekunst Matthias , Mueller Thomas , Weilbacher Andrea , Dengler Michael A. , Bedke Jens , Kruck Stephan , Oren Moshe , Aulitzky Walter E. , van der Kuip Heiko 
Published: January 2013

Abstract
Testicular germ cell tumors (TGCT) are considered a paradigm of chemosensitive tumors. Embryonal carcinoma cells represent the pluripotent entity of TGCTs and are characterized by expression of Oct-4, a key regulator of pluripotency and a determinant of their inherent hypersensitivity to cisplatin. However, the mechanisms underlying this Oct-4–mediated sensitivity are poorly understood. We previously showed that p53 is a major player in cisplatin hypersensitivity and therefore investigated whether Oct-4 may directly affect p53 activity. Despite a significant decrease in sensitivity, depletion of Oct-4 neither did alter cisplatin-induced transactivation of p53 target genes nor its subcellular localization. These data indicate that, rather than directly modulating p53 activity, Oct-4 provides a cellular context that augments the proapoptotic activity of p53. As mitochondrial priming by the Bcl-2 family is a known determinant of chemosensitivity, we compared the constitutive levels of these proteins in Oct-4–positive and -depleted cells. We identified Noxa as the only Bcl-2 family protein to be highly correlated with Oct-4 status and cisplatin sensitivity. Compared with differentiated cells, constitutive Noxa levels were significantly higher in Oct-4–positive cell lines and cancer patient samples. Furthermore, RNA interference–mediated knockdown of Oct-4 resulted in reduced Noxa transcript, in an almost complete loss of constitutive Noxa protein and decreased cisplatin hypersensitivity to a similar extent as did Noxa depletion. In conclusion, our study indicates that Noxa is a central determinant of hypersensitivity to cisplatin. Oct-4–dependent high constitutive levels of this BH3-only protein prime embryonal carcinoma cells to undergo rapid and massive apoptosis in response to p53 activation. Cancer Res; 73(5); 1460–9. ©2012 AACR.