niryuu/sni-each-converted huggingface dataset:
The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002-2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss, and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis.
Output: Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)
Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. Of the 41 nucleotide changes, 12 resulted in conservative changes and 18 produced non-conservative changes. The results suggest that key amino acids in ORF1 may contribute to the phenotype of RespPRRS, which includes increased growth rate on MA-104 cells and decreased virulence in swine. The results provide a genetic basis for future manipulation of a PRRSV reverse genetics system.
Output: Erratum to ''Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains''
As simple organisms with a parasite nature, viruses have become masters in manipulating and subvert cellular components, including host proteins and organelles, to improve viral replication. Therefore, the understanding of viral strategies to manipulate cell function disrupting plant defenses and enhancing viral infection cycles is fundamental to the production of virus-resistant plant lines. After invading susceptible plants, viruses create conditions that favor local and systemic infections by suppressing multiple layers of innate host defenses while use cellular machinery to own benefit. Viral interference in interlinked essential cellular functions results in phenotypic changes and disease symptoms, which debilitates plants favoring infection establishment. Herein in this review, the novelty it will be the discussion about the strategies used by (+) single strand RNA viruses to affect cellular processes and components to improve viral replication, in parallel to overcome plant defenses, favoring disease establishment by applying in one action using the same viral protein to coordinate viral replication and breaking down plant defense. This focus on plant-virus interaction was never done before, and this knowledge has the potential to help in the development of new strategies to produce resistant plants.
Output: Killing two birds with one stone: How do Plant Viruses Break Down Plant Defenses and Manipulate Cellular Processes to Replicate Themselves?
)phenoxy] heptyl]-3-methylisoxazole, inhibits the replication of several picornaviruses (Otto et al., Antimicrob. Ag. Chemother. 27 (1985) 883-886). Measurements of viral RNA synthesis and electron microscopy showed that disoxaril inhibits the replication of poliovirus types 1 and 2 in HeLa cells prior to uncoating by stabilizing the virus capsid: The arrival of viral RNA for new RNA synthesis was inhibited completely only when the inocula were preincubated with disoxaril for 15 min at 37°C at 0.3 Ilg disoxarillml for poliovirus type 1 and 0.03 ug disoxarillml for poliovirus type 2. Simultaneous addition of the compound and virus resulted in reduced inhibition of viral RNA synthesis. The inhibitory effect of the compound could be partially reversed up to 25 min p.i. if the compound was eluted from the cells. Disoxaril pretreated poliovirus was not inhibited from entering HeLa cells (entry by receptor-mediated endocytosis via coated pits and vesicles into endosomes) (d.
Output: Inhibition of an Early Step of Poliovirus Replication by Disoxaril (WIN 51711) Neutralizing Monoclonal Antibodies Obtained After In Vivo Priming with VPl of Poliovirus Type 1 Recognize Epitopes Located Between Amino Acid Residues 93-104 of VPl
The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-a in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-a. Further study indicated that IFN-c+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of costimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.
Output: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells
Correspondence: Canadian Paediatric Society, 100-2305 St Laurent Blvd, Ottawa, Ontario K1G 4J8. E-mail info@cps.ca, website www.cps.ca All Canadian Paediatric Society position statements and practice points are reviewed regularly and revised as needed. Consult the Position Statements section of the CPS website www.cps.ca/en/documents for the most current version. Retired statements are removed from the website. Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.
Output: Position Statement Infection prevention and control in paediatric office settings
Cassiae semen (Leguminosae), a well-known traditional Chinese medicine, has been used for a number of centuries in areas of Southeast Asia, including Korea, Japan and China. The present review aims to provide updated and comprehensive information, on the botany, phytochemistry and pharmacology of Cassiae semen. The available information on Cassiae semen was collected using several different resources, including classic books on Chinese herbal medicine and a number of scientific databases, including the China Academic Journals full-text database, PubMed, SciFinder, the Web of Science and Science Direct. To date >70 chemical compounds have been isolated from Cassiae semen, and the major components have been determined to be anthraquinones, naphthopyrones and volatile oil. The crude extracts and pure compounds of Cassiae semen have been used as effective agents in preclinical and clinical practice due to their beneficial activities, including antihyperlipidemic, antidiabetic, neuroprotective, hepatoprotective, antibacterial, antioxidant and hypotensive activities. With the body of reported data, it has been suggested that Cassiae semen has convincing medicinal potential. However, the pharmacological mechanisms of the main bioactive compounds and the association between structure and activity require further investigation. C. obtusifolia is similar to C. tora in terms of botanical morphology. The two are an annual, erect, stout herb, ~1-2 m in length, and their leaves are paripinnate, typically pubescent and are 4-8 cm in length with a conical gland between each of the two lowest pairs of leaflets. Leaflets are formed of 3 leaf
Output: Cassiae semen: A review of its phytochemistry and pharmacology (Review)
Disaster medical response has historically focused on the prehospital and initial treatment needs of casualties. In particular, the critical care component of many disaster response plans is incomplete. Equally important, routinely available critical care resources are almost always insufficient to respond to disasters that generate anything beyond a 'modest' casualty stream. Large-scale monetary funding to effectively remedy these shortfalls is unavailable. Education, training, and improved planning are our most effective initial steps. We suggest several areas for further development, including dual usage of resources that may specifically augment critical care disaster medical capabilities over time.
Output: ICU = intensive care unit
The Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause severe disease and has pandemic potential. Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2′. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported. However, the relative importance of these sites for MERS-S activation is incompletely understood. Here, we used mutagenic analysis and MERS-S-bearing vectors to study the contribution of specific cleavage sites to S proteindriven entry. We found that an intact S1/S2 site was only required for efficient entry into cells expressing endogenous TMPRSS2. In keeping with a previous study, pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin. In contrast, the S2′ site (RSAR) was required for robust viral entry into all cell lines tested and the integrity of one of the two arginines was sufficient for efficient entry. These findings suggest that cleavage at S2′ is carried out by proteases recognizing a single arginine, most likely TMPRSS2 and cathepsin L. Finally, mutation of the proposed cathepsin L site did not impact viral entry and double mutation of S1/S2 and S2′ site was compatible with cathepsin L-but not TMPRSS2-dependent host cell entry, indicating that cathepsin L can process the S protein at auxiliary sites. Collectively, our results indicate a rigid sequence requirement for S protein activation by TMPRSS2 but not cathepsin L.
Output: Functional analysis of potential cleavage sites in the MERS- coronavirus spike protein
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. J. Dairy Sci. 97 :5035-5044 http://dx. Housing preweaned dairy calves in pairs rather than individually has been found to positively affect behavioral responses in novel social and environmental situations, but concerns have been raised that close contact among very young animals may impair their health. In previous studies, the level of social contact permitted in individual housing has been auditory, visual, or physical contact. It is unclear how these various levels of social contact compare with each other and to pair housing, when their effects on behavior and health are considered, and whether the timing of pair housing has an effect. To investigate this, 110 Holstein calves (50 males, 60 females) in 11 blocks were paired according to birth date. Within 60 h of birth, each pair of calves was allocated to 1 of 5 treatments: individual housing with auditory contact (I), individual housing with auditory and visual contact (V), individual housing with auditory, visual, and tactile contact (T), pair housing (P), or individual housing with auditory and visual contact the first 2 wk followed by pair housing (VP). At 6 wk of age, calves were subjected to a social test and a novel environment test. In the social test, all pair-housed calves (P and VP) had a shorter latency to sniff an unfamiliar calf than did individually housed calves (I, V, and T), whereas calves with physical contact (T, P, and VP) sniffed the unfamiliar calf for longer than calves on the remaining treatments (I and V). In the novel environment test, calves with physical contact (T, P, and VP) had a lower heart rate, and more of these calves vocalized during the test compared with calves without physical contact (I and V). No effect of treatment was found for clinical scores, levels of the 5 most common pathogens in feces, or in development of serum antibodies against the 3 most common respiratory pathogens. Calves housed individually are more fearful of unfamiliar calves than are pair-housed calves. Contrary to common belief, the allowance of physical contact and pair housing had no effects on the health of the calves.
Output: Effects of level of social contact on dairy calf behavior and health
The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected. Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children aged 2-11 y at baseline and when parents thought their child was developing a cold. Parentalrecorded severity of specific symptoms in children with and without a documented viral URI were compared. Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold. A viral etiology was identified in 62 of 108 (57.4%) samples. Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on days 1-4 of the illness. A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9%, and accuracy of 73.3%. Parental impression is only a moderately accurate predictor of viral URI in children. Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies. (Pediatr Res 68: 252-257, 2010)
Output: Development of a Symptom Score for Clinical Studies to Identify Children With a Documented Viral Upper Respiratory Tract Infection
Most significant change in the evolution of the influenza virus is the rapid growth of the Concentrated Animal Feeding Operations (CAFOs) on a global scale. These industrial agricultural operations have the potential of housing thousands of animals in a relatively small area. Emerging Infectious Diseases (EIDs) event can be considered as a shift in the pathogen-host-environment interplay characteristics described by Engering et al. (2013) . These changes in the host-environment and the disease ecology are key to creating novel transmission patterns and selection of novel pathogens with a modification of genetic traits. With the development of CAFOs throughout the world, the need for training of animal caretakers to observe, identify, treat, vaccinate and cull if necessary is important to safeguard public health. The best defense against another pandemic of Emerging Infectious Diseases (EIDs) is the constant monitoring of the livestock and handlers of CAFOs and the live animal markets. These are the most likely epicenter of the next pandemic.
Output: Interaction of the role of Concentrated Animal Feeding Operations (CAFOs) in Emerging Infectious Diseases (EIDS)
a b s t r a c t Nucleocapsid (N) protein gene of turkey coronavirus (TCoV) was expressed in a prokaryotic system and used to develop an enzyme-linked immunosorbent assay (ELISA) for detection of antibody to TCoV. Anti-TCoV hyperimmune turkey serum and normal turkey serum were used as positive or negative controls for optimization of the ELISA. Goat anti-turkey IgG (H+L) conjugated with horseradish peroxidase was used as detector antibody. Three hundred and twenty two turkey sera from the field were used to evaluate the performance of ELISA and determine the cut-off point of ELISA. The established ELISA was also examined with serum samples obtained from turkeys experimentally infected with TCoV. Those serum samples were collected at various time intervals from 1 to 63 days post-infection. The optimum conditions for differentiation between anti-TCoV hyperimmune serum and normal turkey serum were recombinant TCoV N protein concentration at 20 g/ml, serum dilution at 1:800, and conjugate dilution at 1:10,000. Of the 322 sera from the field, 101 were positive for TCoV by immunofluorescent antibody assay (IFA). The sensitivity and specificity of the ELISA relative to IFA test were 86.0% and 96.8%, respectively, using the optimum cut-off point of 0.2 as determined by logistic regression method. Reactivity of anti-rotavirus, anti-reovirus, anti-adenovirus, or anti-enterovirus antibodies with the recombinant N protein coated on the ELISA plates was not detected. These results indicated that the established antibody-capture ELISA in conjunction with recombinant TCoV N protein as the coating protein can be utilized for detection of antibodies to TCoV in turkey flocks.
Output: Recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibody to turkey coronavirus
Background: Tuberculosis (TB) is one of the world's major communicable infectious diseases, and it still imposes a great health burden in developing countries. The development of drug-resistant TB during the treatment increases the treatment complexity, and the long-term pulmonary complications after completing treatment raise the epidemic health burden. This study intended to investigate the utilization of Chinese medicine (CM) for respiratory symptoms by patients with a medical history of TB in Taiwan. Methods: We analyzed a cohort of one million individuals who were randomly selected from the National Health Insurance Research Database in Taiwan. The inclusion criteria of patients (n = 7905) with history of TB (ICD-9-CM codes 010-018 and A02) were: (1) TB diagnosed between January 1, 1997 and December 31, 2010 (2) 18 years old or over (3) Clinical records for at least 2 months with complete demographic information (4) Record of treatment with first-line TB medication prescriptions. CM users for conditions other than respiratory discomforts (n = 3980) were excluded. Finally, a total of 3925 TB patients were categorized as: CM users for respiratory discomforts (n = 2051) and non-CM users (n = 1874). Results: Among the 3925 subjects, 2051 (52.25%) were CM users, and 1874 (44.753%) were non-CM users. Female patients and those who were younger (18-39 y/o) and who lived in urbanized areas relatively tended to be CM users (p < .0001). Most of the CM users (1944, 94.78%) received Chinese medicines. The most commonly prescribed herbal formulas and single herbs were Xiao-Qing-Long-Tang and Radix Platycodonis (Jie-Geng), respectively. The core pattern of Chinese medicines for TB patients consisted of Ma-Xing-Gan-Shi-Tang, Bulbus Fritillariae Thunbergii (Bei-Mu), Radix Platycodonis (Jie-Geng) and Semen Armeniacae (Xing-Ren). Conclusions: The use of CM is popular among patients with a medical history of TB complicated with long-term respiratory discomforts in Taiwan. Further pharmacological investigations and clinical trials are required.
Output: Utilization of Chinese medicine for respiratory discomforts by patients with a medical history of tuberculosis in Taiwan
Human coronaviruses are known to be a common cause of respiratory infections in man. However, the diagnosis of human coronavirus infections is not carried out routinely, primarily because the isolation and propagation of these viruses in tissue culture is difficult and time consuming. The aim of this study was to evaluate the use of recombinant, bacterial expressed proteins in the serodiagnosis of coronavirus infections. Two proteins were examined: the human coronavirus 229E nucleocapsid protein (N), expressed as a fusion protein in the vector pUR and the coronavirus 229E surface glycoprotein (S), expressed as a fusion protein in the vector PROS. The recombinant proteins were used as antigens in Western blot (WB) assays to detect the 229E-specific IgG antibodies and the results were compared with a standard serological method, indirect immunofluorescence. Serum samples of 51 paediatric patients, suffering from acute respiratory illness, and 10 adults, voluntarily infected with human coronavirus, were tested. The semm samples of the adult group had coronavims-specific IgG antibodies in both test systems. In contrast, only 8/51 sera of the paediatric group were positive for coronavirus-specific IgG by both WB and IF and 20/51 sera were positive by WB, but not by IF. The overall incidence of human coronavims infections in the paediatric age group was 55% evaluated by WB analysis and 16% evaluated by IF. This study shows that recombinant human coronavirus 229E proteins are suitable reagents for the epidemiological screening of coronavirus 229E infections. 0166-0934/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDIO166-0934(95)00041-O
Output: Detection of human coronavirus 229E-specific antibodies using recombinant fusion proteins
Proteinchip profiling is a powerful and innovative proteomic technology for the discovery of biomarkers and the development of diagnostic/prognostic assays. On the basis of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen's proteinchip system offers a single, unified, and high throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell. The study of proteomics helps to better understand the mechanism of a disease. Remarkable findings in disease biomarkers have shed light on the early diagnosis, monitoring, and prognosis of various diseases, especially for cancer. In this paper, the development and technology of SELDI-TOF MS are introduced. The research progress and encouraging research results in malignancies, infectious diseases, neurological diseases, and diabetes mellitus using SELDI-TOF MS are reviewed. This paper concludes by evaluating the pros and cons, and the future perspectives are also expounded.
Output: Research Progress in SELDI-TOF MS and Its Clinical Applications
Background: The continuing spread of the newly emerged H7N9 virus among poultry in China, as well as the possibility of human-to-human transmission, has attracted numerous efforts to develop an effective vaccine against H7N9. The use of nanoparticles in vaccinology is inspired by the fact that most pathogens have a dimension within the nano-size range and therefore can be processed efficiently by the immune system, which leads to a potent immune response. Herein, we report a facile approach to increase antigen size to achieve not only fast but also effective responses against the recombinant HA/H7N9 protein via a simple conjugation of the protein onto the surface of nanodiamond particles. In this study, trimeric Haemagglutinin (H7) that is transiently expressed in N. benthamiana was purified using affinity chromatography, and its trimeric state was revealed successfully by the cross-linking reaction. The trimeric H7 solution was subsequently mixed with a nanodiamond suspension in different ratios. The successful conjugation of the trimeric H7 onto the surface of nanodiamond particles was demonstrated by the changes in size and Zetapotential of the particles before and after protein coating, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and Western-blot analysis. Next, biofunction of the protein-nanodiamond conjugates was screened using a haemagglutination assay. A mixture containing 5 µg of trimeric H7 and 60 µg of nanodiamond corresponds to a ratio of 1:12 (w/w) of agglutinated chicken red blood cells at HA titer of 1024, which is 512-fold higher than the HA titer of free trimeric H7. After the 2nd and 3rd immunization in mice, ELISA and Western blot analyses demonstrated that the physical mixture of trimeric H7 protein and nanodiamond (1:12, w/w) elicited statistically significant stronger H7-specific-IgG response demonstrated by higher amounts of H7N9-specific IgG (over 15.4-fold with P < 0.05 after the second immunization). These results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development.
Output: Nanodiamond enhances immune responses in mice against recombinant HA/ H7N9 protein
One sentence summary: Disruptions of school and work due to heavy snowfall in the Seattle metro area reduced the total size of respiratory virus epidemics by up to 9%. BACKGROUND: Unusually high snowfall in western Washington State in February 2019 led to widespread school and workplace closures. We assessed the impact of social distancing caused by this extreme weather event on the transmission of respiratory viruses. METHODS: Residual specimens from patients evaluated for acute respiratory illness at hospitals in the Seattle metropolitan area were screened for a panel of respiratory viruses. Transmission models were fit to each virus, with disruption of contact rates and care-seeking informed by data on local traffic volumes and hospital admissions. RESULTS: Disruption in contact patterns reduced effective contact rates during the intervention period by 16% to 95%, and cumulative disease incidence through the remainder of the season by 3% to 9%. Incidence reductions were greatest for viruses 1 . CC-BY-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Title: Effects of weather-related social distancing on city-scale transmission of respiratory viruses (limit 96 characters)
Replication of avian infectious bronchitis virus in permissive BHK-21 cells is blocked when these cells are enucleated or irradiated with ultraviolet light prior to infection, or if cells sre treated with a-amanitin during the virus growth cycle. This coronavirus, like influenza virus, can replicate normally in the presence of cr-amanitin in Chinese hamster ovary cells which possess a drug-resistant RNA polymerase II. These findings indicate that avian infectious bronchitis virus requires the intact cell nucleus and one or more host transcriptional functions for productive infections, Preliminary data suggest that these cellular functions involve some aspect of virus-directed RNA synthesis.
Output: The Coronavirus Avian Infectious Bronchitis Virus Requires the Cell Nucleus and Host Transcriptional Factors
Serine proteases of the trypsin-like family have long been recognized to be critical effectors of biological processes as diverse as digestion, blood coagulation, fibrinolysis, and immunity. In recent years, a subgroup of these enzymes has been identified that are anchored directly to plasma membranes, either by a carboxy-terminal transmembrane domain (Type I), an amino-terminal transmembrane domain with a cytoplasmic extension (Type II or TTSP), or through a glycosylphosphatidylinositol (GPI) linkage. Recent biochemical, cellular, and in vivo analyses have now established that membrane-anchored serine proteases are key pericellular contributors to processes vital for development and the maintenance of homeostasis. This chapter will review our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease.
Output: Membrane-anchored serine proteases in health and disease
A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin-Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1- half-maximal effective concentrations of 17.4-21.1 lM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900 lM. To investigate the structure-activity relationships, two dozens of the hit analogs were synthesized. Among them, 15g, 15j, 15q, 15s, 15t and 15x had anti-influenza viral activity comparable or superior to that of the initial hit. The anti-influenza viral compounds efficiently suppressed not only viral protein level of the infected cells but also production of viral progeny in the culture supernatants in a dose-dependent manner. Based on a mode-of-action study, they did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors.
Output: Synthesis and anti-influenza virus activity of 4-oxo-or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Common Indications • Cytologic examination of exudates, blood film, tissue imprint, aspiration biopsy, or wet mount of hair is indicated when bacterial and fungal diseases (and occasionally rickettsial and viral diseases) are suspected.
Output: Microbiology and Infectious Disease
The CyP40 protein encoded by PPID gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The CyP40 protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant drug cyclosporin A (CsA). In this study, we created keratinocyte cell lines with CyP40 being stably knocked down using viral particles containing shRNA for CyP40 which knocked down the expression level of CyP40 transcripts by 90 to 99%. The proliferation rates of the cell lines with silenced CyP40 were decreased compared to the control cells. After UVA irradiation, the rate of apoptosis was found to be significantly lower in CyP40 silenced cell lines than it was in control cells. Moreover, mitochondrial membrane potential (MMP) was found to be less dissipated and mitochondrial permeability transition pore (MPTP) less active in cells with knocked down CyP40 than in control cells after UVA irradiation. Also, less mitochondrial superoxide was detected in the cells with silenced CyP40 compared to control cells after UVA exposure. Moreover, silencing of CyP40 partially modulates expression of key genes involved in mitochondrial pore formation including CyPD, ANTs and VDAC family members. The ability of CyP40 to regulate UV induced apoptosis implicates this protein as a potential target for therapy in cancer cells. CyP40; stable CyP40 knock-down; mitochondrial membrane potential; mitochondrial pore opening; UVA-induced apoptosis; reactive oxygen species; keratinocytes Cyclophilin proteins (CyPs) are ubiquitous proteins with peptidyl-prolyl cis-trans isomerase activity [1]. CyPs are highly conserved among all types of species including animals, plants, fungi and bacteria with a shared isomerase domain of approximately 109 amino acids. In humans, there are sixteen CyPs including cyclophilin 40, a 40kD cytosolic protein (CyP40)
Output: Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes
Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly.
Output: Viroporins, Examples of the Two-Stage Membrane Protein Folding Model
This paper is dedicated to Professor Joep Lange, a Dutch pioneer in AIDS research and a great protagonist of access to effective antiretroviral therapy for all. On July 17 this year, Joep died in the plane crash in Ukraine on his way to the AIDS conference in Australia. a b s t r a c t At any given moment, our body is under attack by a large variety of pathogens, which aim to enter and use our body to propagate and disseminate. The extensive cellular and molecular complexity of our immune system enables us to efficiently eliminate invading pathogens or at least develop a condition in which propagation of the microorganism is reduced to a minimum. Yet, the evolutionary pressure on pathogens to circumvent our immune defense mechanisms is immense, which continuously leads to the development of novel pathogenic strains that challenge the health of mankind. Understanding this battle between pathogen and the immune system has been a fruitful area of immunological research over the last century and will continue to do so for many years. In this review, which has been written on the occasion of the 50th anniversary of the Dutch Society for Immunology, we provide an overview of the major contributions that Dutch immunologists and infection biologists have made in the last decades on the inflammatory response to viral, bacterial, fungal or parasitic infections. We focus on those studies that have addressed both the host and the pathogen, as these are most interesting from an immunological point of view. Although it is not possible to completely cover this comprehensive research field, this review does provide an interesting overview of Dutch research on inflammatory responses to infection.
Output: Inflammatory responses to infection: The Dutch contribution
Background: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are many subtypes of IAV but only a few seem to be able to adapt to humans and to cause disease. In 2013, an H7N9 IAV subtype emerged in China that does not cause clinical symptoms in its chicken host but leads to severe infections when transmitted into humans. Since 2013, there have been six epidemic waves of H7N9 with 1567 laboratory-confirmed human infections and 615 deaths. Pathogenicity of IAV is complex, but a crucial feature contributing to virulence is the activation of the hemagglutinin (HA) fusion protein by host proteases that triggers membrane fusion and leads to subsequent virus propagation. : 293T, VERO, and MDCK cells were used to conduct Western blot analysis, immunofluorescence assays, and pseudoparticle and live virus infections, and to evaluate H7N9 HA cleavage-activation. Results/Conclusions: We show that human matriptase/ST 14 is able to cleave H7N9 HA. Cleavage of H7N9 HA expressed in cell culture results in fusogenic HA and syncytia formation. In infection studies with viral pseudoparticles carrying matriptase/ ST 14-activated H7N9 HA, we observed a high infectivity of cells. Finally, human matriptase/ST 14 also activated H7N9 live virus which resulted in high infectivity. Our data demonstrate that human matriptase/ST 14 is a likely candidate protease to promote H7N9 infections in humans.
Output: Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture
Epidemiology Middle east respiratory syndrome coronavirus Mathematical modelling South Korea Background: Effective countermeasures against emerging infectious diseases require an understanding of transmission rate and basic reproduction number (R 0 ). R 0 for severe acute respiratory syndrome is generally considered to be >1, whereas that for Middle East respiratory syndrome (MERS) is considered to be <1. However, this does not explain the large-scale outbreaks of MERS that occurred in Kingdom of Saudi Arabia (KSA) and South Korean hospitals. Aim: To estimate R 0 in nosocomial outbreaks of MERS. Methods: R 0 was estimated using the incidence decay with an exponential adjustment model. The KSA and Korean outbreaks were compared using a line listing of MERS cases compiled using publicly available sources. Serial intervals to estimate R 0 were assumed to be six to eight days. Study parameters [R 0 and countermeasures (d)] were estimated by fitting a model to the cumulative incidence epidemic curves using Matlab. Findings: The estimated R 0 in Korea was 3.9 in the best-fit model, with a serial interval of six days. The first outbreak cluster in a hospital in Pyeongtaek had an R 0 of 4.04, and the largest outbreak cluster in a hospital in Samsung had an R 0 of 5.0. Assuming a six-day serial interval, the KSA outbreaks in Jeddah and Riyadh had R 0 values of 3.9 and 1.9, respectively. Conclusion: R 0 for the nosocomial MERS outbreaks in KSA and South Korea was estimated to be in the range of 2e5, which is significantly higher than the previous estimate of <1. Therefore, more comprehensive countermeasures are needed to address these infections.
Output: High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea
Mouse Hepatitis Virus (MHV) is a single-stranded positive sense RNA virus with the ability to promote acute and chronic diseases in mice. The MHV spike protein (S) is a major virulence determinant which in addition to binding to cellular receptors to mediate cell entry and facilitate virus spread to adjacent cells by cell-cell fusion, also is a molecular mimic of the Fc␥RII receptor. This molecular mimicry of Fc␥RII by the MHV S protein is also exhibited by other lineage 2a betacoronaviruses, with the exception of the human coronavirus HCoV-OC43. In this work we undertook a mutational analysis to attempt to identify specific amino acid sequences within the spike glycoprotein crucial for molecular mimicry of Fc␥RII. Although we were unsuccessful in isolating mutant viruses which were specifically defective in that property, we identified several mutations with interesting phenotypes. Mutation of the cysteine in position 547 to alanine and alanine replacements at residues 581-586 was lethal. Replacing proline 939 with the corresponding HCoV-OC43 residue, leucine, decreased the ability MHV to induce cell-cell fusion, providing experimental support for an earlier proposal that residues 929-944 make up the fusion peptide of the MHV S protein.
Output: Identification of novel functional regions within the spike glycoprotein of MHV-A59 based on a bioinformatics approach
Immunohistochemical, viral and bacterial isolation techniques were used to study the distribution and localization of porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus (H.) parasuis in experimentally infected pigs. Thirty pigs seronegative to PRRSV and H. parasuis were divided into four groups. Group A pigs (10 animals) were inoculated with both virus and bacteria; group B pigs (10 animals) were inoculated with bacteria, group C pigs (five animals) were inoculated with virus and group D pigs (five animals) were kept as negative controls. All pigs of groups A and C became infected with PRRSV, according to virological techniques used (immunohistochemistry, virus isolation and virus serology). Lung, heart and tonsils were the most frequently immunolabeled tissues, and monocyte/macrophage lineage cells were the target for PRRSV in all tissues. All pigs in groups A and B also became infected with H. parasuis based on immunohistochemical and bacterial isolation results. Serosal surfaces, lung and tonsils were the most frequently immunolabeled tissues, and bacteria were found in monocyte/macrophage lineage cells as well as within neutrophil cytoplasm. No differences in terms of bacterial distribution or localization in tissues of pigs of groups A and B were detected. These results suggest that there is no influence of the previous infection with PRRSV in the occurrence of H. parasuis infection. # 1999 Elsevier Science B.V. All rights reserved. 0378-1135/99/$ ± see front matter # 1999 Elsevier Science B.V. All rights reserved. PII S 0 3 7 8 -1 1 3 5 ( 9 8 ) 0 0 2 6 0 -0
Output: Porcine reproductive and respiratory syndrome virus and Haemophilus parasuis antigen distribution in dually infected pigs
Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current views on how aging influences the factors that impact T cell function and how this can affect the immune response to infections, vaccinations, and tumors.
Output: Effects of aging on T cell function
B . A. Summers and M . J . G . Appel . Growth of canine distemper virus in cultured astrocytes : relationship to in vivo persistence and disease . Microbial Pathogenesis 1990 ; 8 : 71-82 . Canine distemper virus (CDV) causes an encephalomyelitis in dogs which varies with the viral strain . The CDV Cornell A75-17 strain produces a delayed, subacute to chronic, demyelinating CNS disease . In contrast, the Snyder Hill (CDV-SH) strain-associated neurological disease is more acute in onset, is usually non-demyelinating and primarily produces lesions in the gray matter . In these studies we describe the effects of these two virulent and one avirulent CDV strain, Rockborn (CDV-RO), on astrocytes in dissociated canine brain cell cultures . In multiple replicate experiments, astrocytes were infected most rapidly by CDV-RO [100% of astrocytes were infected by 14 days post-inoculation (p .i .)] . This strain caused severe cytopathic effect (CPE) and cytolysis . CDV-SH similarly produced a rapid infection of the astrocytes . In contrast . CDV A75-17 infected less than 25% of the astrocyte population during the first 28 days p .i . (±7 days) ; after 28 days p .i ., a rapid rise in astrocyte infection occurred . Both virulent viruses caused astrocytic syncytial formation but did not cause cytolysis of the astrocyte population as was observed with the attenuated virus . Titers of infectious virus, released into the supernatant fluid, reflected the degree of astrocyte infection . Virus released by the cultures late in CDV A75-17 infection showed enhanced ability to infect newly derived astrocytes ; in contrast, brain cell passaged CDV-SH did not show increased growth in these cells . These results show that (1) there is a difference in growth rate, CPE and capacity for adaptation of three different CDV strains in astrocytes in vitro, and (2) some aspects of the disease (such as persistence in white matter) produced by the virulent strains in vivo may be related to the course of astrocyte infection observed in vitro .
Output: Growth of canine distemper virus in cultured astrocytes : relationship to in vivo persistence and disease
Waddlia chondrophila, an obligate intracellular bacterium of the Chlamydiales order, is considered as an agent of bovine abortion and a likely cause of miscarriage in humans. Its role in respiratory diseases was questioned after the detection of its DNA in clinical samples taken from patients suffering from pneumonia or bronchiolitis. To better define the role of Waddlia in both miscarriage and pneumonia, a tool allowing large-scale serological investigations of Waddlia seropositivity is needed. Therefore, enriched outer membrane proteins of W. chondrophila were used as antigens to develop a specific ELISA. After thorough analytical optimization, the ELISA was validated by comparison with micro-immunofluorescence and it showed a sensitivity above 85% with 100% specificity. The ELISA was subsequently applied to human sera to specify the role of W. chondrophila in pneumonia. Overall, 3.6% of children showed antibody reactivity against W. chondrophila but no significant difference was observed between children with and without pneumonia. Proteomic analyses were then performed using mass spectrometry, highlighting members of the outer membrane protein family as the dominant proteins. The major Waddlia putative immunogenic proteins were identified by immunoblot using positive and negative human sera. The new ELISA represents an efficient tool with high throughput applications. Although no association with pneumonia and Waddlia seropositivity was observed, this ELISA could be used to specify the role of W. chondrophila in miscarriage and in other diseases.
Output: Undressing of Waddlia chondrophila to enrich its outer membrane proteins to develop a new species-specific ELISA