niryuu/sni-each-converted huggingface dataset:
Background: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. Methods: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. : Among 174 patients (132 men [76 %], age 63 [53-75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. Conclusions: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.
Output: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia
The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We used serological methods and quantitative real-time PCR to test free-ranging and captive Namibian cheetahs for the presence of feline leukemia virus (FeLV), a gammaretrovirus that can be highly aggressive in populations with low genetic diversity, such as cheetahs. We also assessed the presence of antibodies to other gammaretroviruses and the responses to a FeLV vaccine developed for domestic cats. Up to 19% of the free-ranging cheetahs, 27% of the captive nonvaccinated cheetahs, and 86% of the captive vaccinated cheetahs tested positive for FeLV antibodies. FeLV-antibody-positive freeranging cheetahs also tested positive for Rauscher murine leukemia virus antibodies. Nevertheless, FeLV was not detectable by quantitative real-time PCR and no reverse transcriptase activity was detectable by product-enhanced reverse transcriptase assay in the plasma of cheetahs or the supernatants from cultures of peripheral blood mononuclear cells. The presence of antibodies to gammaretroviruses in clinically healthy specimens may be caused either by infection with a low-pathogenic retrovirus or by the expression of endogenous retroviral sequences. The strong humoral immune responses to FeLV vaccination demonstrate that cheetahs can respond to the vaccine and that vaccination against FeLV infection may be beneficial should FeLV infection ever become a threat, as was seen in Iberian lynx and Florida panthers.
Output: Gammaretrovirus-Specific Antibodies in Free-Ranging and Captive Namibian Cheetahs
Background: Coccidiosis due to Eimeria spp. infections in lambs causes increased mortality and substantial production losses, and anticoccidials are important for control of the infection. Anticoccidial resistance has been reported in poultry and swine, and we recently described reduced toltrazuril efficacy in ovine Eimeria spp. in some Norwegian sheep farms using a newly developed faecal oocyst count reduction test (FOCRT). The aim of the present study was to use a controlled efficacy trial to assess the efficacy of toltrazuril against a field isolate suspected of being resistant. Methods: Twenty lambs, 17-22 days old and raised protected against exposure to coccidia, were infected with a field isolate of 100,000 Eimeria spp. oocysts. This isolate was obtained from a farm with a previously calculated drug efficacy of 56% (95% confidence interval: -433.9 to 96.6%). At day 7 post-infection, 10 of the lambs were orally treated with 20 mg/kg toltrazuril (Baycox Sheep vet., Bayer Animal Health), while the other 10 lambs (controls) were given physiological saline. Clinical examinations were conducted, and weight gains recorded. Daily faecal samples were scored for diarrhoea on a scale from 1 to 5, and oocyst excretion was determined using a modified McMaster technique. Oocysts were morphologically identified to species level. At 17-24 days post-infection, the lambs were euthanized and necropsied. Results: The tested Eimeria isolate was resistant against toltrazuril, and resistance was seen in both pathogenic and non-pathogenic species. In addition, no significant differences in faecal score, growth, gross pathology or histological changes were identified between the two groups. The pathogenic E. ovinoidalis was the dominant species, and no significant difference in the individual prevalence of E. ovinoidalis post-treatment was found between treated (66.9%) and control lambs (61.9%). Other species identified included E. crandallis/weybridgensis, E. parva, E. marsica, E. faurei, E. pallida, E. ahsata and E. bakuensis. Conclusions: This study confirms toltrazuril resistance in ovine Eimeria spp.; in addition, the data support the use of FOCRT as an appropriate tool for field evaluation of anticoccidial efficacy. Due to limited anticoccidial treatment alternatives, these findings may have important implications for the sheep industry, particularly in northern Europe.
Output: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp
To explore the critical genes associated with infectious bronchitis virus (IBV) virulence, we compared the genome sequences of virulent YN strain and its attenuated strain aYN. Accumulation of mutations in the S gene and the accessory gene 5a were observed, suggesting a potential role in the loss of viral pathogenicity. Two recombinant IBVs (rIBVs) with replacement of the S gene or 5a with corresponding regions from aYN were rescued to verify this speculation. Embryo mortality time/rate showed that rYN-S-aYN and rYN-5a-aYN had an attenuated phenotype in ovo. Replication assay in ovo and in vitro demonstrated the rIBVs had similar replication patterns with wild-type rIBV. Both rIBVs showed reduced mortality, tissue lesions and tissue virus titers in chicken. In conclusion, S gene and 5a accessory gene are responsible for the attenuation of virulent IBV. Insight into the genes responsible for virus attenuation will facilitate the development of future vaccines against IBV.
Output: S gene and 5a accessory gene are responsible for the attenuation of virulent infectious bronchitis coronavirus
In this chapter, we show the presence of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1) in nasal mucosa. It is suggested that t-PA synthesized in mucous cells is promptly secreted and modifies the watery nasal discharge in allergic rhinitis and that u-PA activity may help with the passage of large amounts of rhinorrhea by reducing its viscosity. Furthermore, we clarify the relation between fibrinolytic components and the pathology of allergy, particularly during the development of nasal allergy and nasal tissue changes. Wild-type (WT) mice can develop nasal allergy for ovalbumin (OVA) sensitization, but PAI-1-deficient mice (PAI-T^") cannot. The production of specific immunoglobulins IgGl and IgE in the serum and production of interleukins IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-l"^" mice, these reactions were absent, and specific IgG2a in serum and interferon-y in splenocyte culture medium increased significantly. Histopathologically, there was marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-l"^" mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-l"^" mice was down-regulated and the immune response shifted from Th2-dominant reaction to a Thl-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in the immune response.
Output: Role of Fibrinolysis in the Nasal System TAKAYUKI SEJIMA AND YOICHI SAKATA^
Background: Kawasaki disease (KD) becomes one of the common diseases in Korea. Changes in clinical features and laboratory findings of KD were evaluated over a period of 10 years. Methods: We reviewed the medical records of KD patients and compared the clinical and laboratory features of two KD patient groups: those admitted from 2000 to 2004 (group A, 284 cases) and those admitted from 2010 to 2014 (group B, 331 cases). Results: There were a total of 615 KD patients (mean age: 29.7 months; male-to-female ratio = 1.6:1), including 228 incomplete KD patients. Incomplete KD patients had milder values in some laboratory indices. The preadmission and total fever durations were longer in group A than in group B. The proportion of incomplete KD was higher in group B, but incidence of coronary artery lesions (CALs) was lower. For laboratory indices, the C-reactive protein and follow-up platelet values were lower, and the hemoglobin and albumin values were higher in group B. The same clinical and laboratory findings were confirmed in the KD subgroups; those with the same fever duration of 5 or 6 days and same ages, those with complete KD, and those with incomplete KD in the two different time periods. Conclusions: Our findings suggest that clinical features of KD tend to be milder over time and manifest in a higher incidence of incomplete KD, lower incidence of CALs, and less severe laboratory findings in recent KD patients in Korea compared with their historic counterparts.
Output: Changes in clinical and laboratory features of Kawasaki disease noted over time in Daejeon, Korea
FilmArray Respiratory Panel (RP) (Idaho Technology, Inc., Salt Lake City, UT, USA) performance was retrospectively evaluated in respiratory samples collected from neonates in 2 reference neonatology units. Using the FilmArray RP assay, 121/152 (79.6%) samples were positive for at least 1 respiratory virus, while 31/ 152 (20.4%) were negative. FilmArray RP results were concordant in 68/72 (94.4%) respiratory samples tested with laboratory-developed real-time PCR assays, while in 4/72 (5.6%) samples, the FilmArray RP assay detected an additional virus (2 human rhinovirus/enterovirus and 2 bocavirus). In addition, FilmArray RP results for 70 of 80 (87.5%) respiratory samples tested were concordant with the Seegene Seeplex RV15® detection assay (Seegene, Inc., Seoul, South Korea), while 10/80 (12.5%) were discordant. The advantages of the FilmArray RP are the rapid detection of respiratory viruses (1 hour), the wide number of pathogens detectable in a single assay, and the reduced hands-on time.
Output: FilmArray® respiratory panel performance in respiratory samples from neonatal care units
The demands of structural and functional genomics for large quantities of soluble, properly folded proteins in heterologous hosts have been aided by advancements in the Weld of protein production and puriWcation. Escherichia coli, the preferred host for recombinant protein expression, presents many challenges which must be surmounted in order to over-express heterologous proteins. These challenges include the proteolytic degradation of target proteins, protein misfolding, poor solubility, and the necessity for good puri-Wcation methodologies. Gene fusion technologies have been able to improve heterologous expression by overcoming many of these challenges. The ability of gene fusions to improve expression, solubility, puriWcation, and decrease proteolytic degradation will be discussed in this review. The main disadvantage, cleaving the protein fusion, will also be addressed. Focus will be given to the newly described SUMO fusion system and the improvements that this technology has advanced over traditional gene fusion systems. 
Output: SUMO fusion technology for diYcult-to-express proteins
Type I interferons (IFNs) are essential to the clearance of viral diseases, however, a clear distinction between genes upregulated by direct virus-cell interactions and genes upregulated by secondary IFN production has not been made. Here, we investigated differential gene regulation in ferrets upon subcutaneous administration of IFN-α2b and during SARS-CoV infection. In vivo experiments revealed that IFN-α2b causes STAT1 phosphorylation and upregulation of abundant IFN response genes (IRGs), chemokine receptors, and other genes that participate in phagocytosis and leukocyte transendothelial migration. During infection with SARS-CoV not only a variety of IRGs were upregulated, but also a significantly broader range of genes involved in cell migration and inflammation. This work allowed dissection of several molecular signatures present during SARS-CoV which are part of a robust IFN antiviral response. These signatures can be useful markers to evaluate the status of IFN responses during a viral infection and specific features of different viruses.
Output: Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation
Animal Health Ireland has produced clear guidelines for the control of Bovine Viral Diarrhoea (BVD) infection in Irish cattle herds. In the course of developing these guidelines it was clear that a framework for regional and/or national BVD control would be required to increase the uptake of BVD control at farm level and reduce the overall prevalence of the disease. This paper assessed the economic impact of BVD, epidemiological aspects of the disease to its control, models of BVD control, international experiences of BVD control programmes. The technical knowledge and test technology exists to eradicate BVD. Indeed, many countries have successfully and others are embarking on control of the disease. The identification and prompt elimination of PI cattle will form the basis of any control programme. The trade of such animals must be curtailed. Pregnant and potentially pregnant carrying PI foetuses pose a significant threat. International experience indicates systematic, well coordinated programmes have the most success, while voluntary programmes can make good initial progress but ultimately fail. The farming community must buy into any proposed programme, and without their support, failure is likely. To buy into the programme and create such a demand for BVD control, farmers must first be well informed. It is likely that stemming economic loss and improving productivity will be the primary motivator at individual farm level.
Output: Considerations on BVD eradication for the Irish livestock industry
Background: In last three years, 96 suspected poultry farms from different provinces in China were diagnosed for avian infectious bronchitis (IB) survey. Finally, 221 IBV strains were confirmed by dwarf embryo test and RT-PCR assay. By virus recovery trials, 187 of the isolates caused the birds died or distressed from nephritis, which was accordant with the clinical record. Results: Based on epidemiology analysis of recent field isolates of nephropathogenic IB in vaccinated farms in China, YL6 strain were used for vaccination and evaluated by antibody titer and challenge tests. The immunoprotection test indicated that the practical application of vaccine based on the recent field strains could finely facilitate controlling the nephropathogenic IB. Conclusions: Our study was aim at setting a guide for safeguard against nephropathogenic IBV-caused disease in China.
Output: Epidemiology and immunoprotection of nephropathogenic avian infectious bronchitis virus in southern China
The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate. Citation Rozo M, Gronvall GK. 2015. The reemergent 1977 H1N1 strain and the gain-offunction debate. mBio 6(4):e01013-15.
Output: The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate
Background: The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. Aims: This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. Sources: A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. Content: We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. Implications: mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged. E. Pelfrene, Clin Microbiol Infect 2019;25:60
Output: Monoclonal antibodies as anti-infective products: a promising future?
Background. Distinguishing between bacterial and viral lower respiratory tract infection (LRTI) remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods. We performed whole blood transcriptional analysis in 118 patients (median age [interquartile range], 61 [50-76] years) hospitalized with LRTI and 40 age-matched healthy controls (median age, 60 [46-70] years). We applied class comparisons, modular analysis, and class prediction algorithms to identify and validate diagnostic biosignatures for bacterial and viral LRTI. Results. Patients were classified as having bacterial (n = 22), viral (n = 71), or bacterial-viral LRTI (n = 25) based on comprehensive microbiologic testing. Compared with healthy controls, statistical group comparisons (P < .01; multiple-test corrections) identified 3376 differentially expressed genes in patients with bacterial LRTI, 2391 in viral LRTI, and 2628 in bacterial-viral LRTI. Patients with bacterial LRTI showed significant overexpression of inflammation and neutrophil genes (bacterial > bacterial-viral > viral), and those with viral LRTI displayed significantly greater overexpression of interferon genes (viral > bacterial-viral > bacterial). The K-nearest neighbors algorithm identified 10 classifier genes that discriminated between bacterial and viral LRTI with a 95% sensitivity (95% confidence interval, 77%-100%) and 92% specificity (77%-98%), compared with a sensitivity of 38% (18%-62%) and a specificity of 91% (76%-98%) for procalcitonin. Conclusions. Transcriptional profiling is a helpful tool for diagnosis of LRTI.
Output: Superiority of Transcriptional Profiling Over Procalcitonin for Distinguishing Bacterial From Viral Lower Respiratory Tract Infections in Hospitalized Adults
Bioaerosols exposure can lead to many adverse health effects and even result in death if highly infectious agents involved. Apparently, there is a great need for rapid detection of bioaerosols, for which air sampling often is the first critical step. However, currently available samplers often either require an external power and/or with low sampling flow rate, thus falling short of providing a practical solution when response time is of great concern. Here, we have designed and evaluated a new portable high volume bioaerosol sampler named as HighBioTrap through optimizing its operating parameters. The sampler was operated at a sampling flow rate of 1200 L/min, with an impaction velocity of about 10.2 m/s (S/W = 1.5, T/ W = 1), while the weight of the sampler is about 1.9 kg. The performances of the HighBioTrap sampler were tested both in lab controlled and natural environments (outdoor and indoor environments in a university building) along with the reference sampler-the BioStage impactor using aerosolized Polystyrene (PS) uniform microspheres of various sizes, aerosolized bacteria and also ambient air particles. The microbial community structures of collected culturable bacterial aerosol particles both by the HighBioTrap and the BioStage impactor in the natural environments were analyzed using gene sequence method. Experimental results with PS particles showed the HighBioTrap has a cutoff size of~2 µm. The widely used impactor design equation was found to be not applicable for predicting the performance of the HighBioTrap due to its large Reynolds number. When sampling aerosolized individual Pseudomonas fluorescens and Bacillus subtilis bacterial particles, the HighBioTrap had physical collection efficiencies of 10% and 20%, respectively. Despite the higher desiccation effects introduced by higher flow rate, the HighBioTrap was shown to obtain a higher microbial diversity than the BioStage impactor for both in outdoor and indoor environments given the same sampling time (p < 0.01). Our data also showed that most of the desiccation effects might have occurred between 3 and 5 min of the sampling and an impaction velocity of around 10 m/s might be a close-to-optimal impaction velocity for collecting most environmental bacterial aerosols while maximally preserving their culturability. This work contributes to our understanding of microbial sampling stress (impaction velocity and sampling time), while developing a portable high volume sampler. The HighBioTrap sampler could find its great efficiencies in qualitative microbial aerosol detection and analysis, such as investigation of microbial aerosol diversity for a particular environment, or when the low level of pathogens is present and detection time is of great concern.
Output: A high-flow portable biological aerosol trap (HighBioTrap) for rapid microbial detection
Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors expand into new geographic ranges. Members of the alphavirus genus tend to induce clinical disease characterized by rash, arthralgia, and arthritis (chikungunya virus, Ross River virus, and Semliki Forest virus) or encephalomyelitis (eastern equine encephalitis virus, western equine encephalitis virus, and Venezuelan equine encephalitis virus), though some patients who recover from the initial acute illness may develop long-term sequelae, regardless of the specific infecting virus. Studies examining the natural disease course in humans and experimental infection in cell culture and animal models reveal that host genetics play a major role in influencing susceptibility to infection and severity of clinical disease. Genome-wide genetic screens, including loss of function screens, microarrays, RNA-sequencing, and candidate gene studies, have further elucidated the role host genetics play in the response to virus infection, with the immune response being found in particular to majorly influence the outcome. This review describes the current knowledge of the mechanisms by which host genetic factors influence alphavirus pathogenesis and discusses emerging technologies that are poised to increase our understanding of the complex interplay between viral and host genetics on disease susceptibility and clinical outcome.
Output: Genetic control of alphavirus pathogenesis
Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system (CNS) principally in young adults. Although its etiology is as yet unknown current evidence suggests that tissue damage is mediated by autoimmune T cells. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), has demonstrated that myelin basic protein (MBP)-or proteolipid protein (PLP)-specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE have shown that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon-~, and tumor necrosis factor-c@3. Understanding the pathogenetic steps in lesion development at the molecular level led to highly specific immunotherapies for EAE targeting each individual molecule. It has been the hope of many investigators that immunological events resembling those in EAE can be found in patients with MS and that the specific immunotherapies effective in EAE could also be applied to MS. However, to date, the evidence for a unique immunological abnormality in MS is not strong. Although MBP-and PLP-specific T cells with properties similar to those that are encephalitogenic in animals can be isolated from patients, they are not specific for MS and occur with similar frequency in controls. In addition, the variability in specificity and TCR usage has raised questions regarding the relevance of these cells in patients. The importance of the T cell responses to myelin antigens in MS may not be established until the effects of abrogating their activity through specific therapies targeting the trimolecular complex (TMC) have been demonstrated. Consequently, attention has begun to focus on modifying the biology of the MS lesion rather than targeting the initiating event at the level of the TMC, and the success of this approach is reflected by the effect of interferon-/3 on lesion development in MS. The recent approval for the use of interferon-/3 for the treatment of relapsing-remitting MS has raised great interest in examining novel strategies for immunotherapies in MS. The Correspondence to: H. McFarland 2 R. Martin, H. McFarland basic concepts as well as the current candidates for such new immunotherapies will be outlined in this short review.
Output: Springer Seminars in Immunopathology Experimental immunotherapies for multiple sclerosis
Objective The aim of this study was to explore the prevalent characteristics of HBoV1 and its co-infection. Methods PCR was used to detect HBoV1-DNA (HBoV1) and other viruses. A multivariate logistic regression model was used to explore possibility of co-detected for related viruses. The positivity rates in Nanjing and Lanzhou were 9.38% (74/789) and 11.62% (161/1386), respectively (P>0.05). The HBoV1 positive group was younger than negative group (P<0.05). Seasonal differences were noted, with a higher frequency of infection in December and July. HBoV1-positive children [72.34% (169/235)] were co-infected with other respiratory viruses. Multifactorial analysis showed no correlations between HBoV1 and the clinical classification, region, gender, age, or treatment as an outpatient or in a hospital. Correlations were identified between HBoV1 infections with ADV (OR=1.53, 95% CI 1.03-2.28), RSV (OR=0.71, 95% CI 0.52-0.98), and IFVA (OR=1.77, 95% CI 1.00-3.13). Conclusions Presence of HBoV1 in nasopharyngeal aspirates did not correlate with region or gender, although the prevalence of HBoV1 was higher in younger children. There were no correlations between HBoV1 and other variables, except for the season and ADV, RSV, or IFVA infections.
Output: Original Article Detection of Human Bocavirus in Children with Acute Respiratory Tract Infections in Lanzhou and Nanjing, China *
Myeloid cells represent a diverse range of innate leukocytes that are crucial for mounting successful immune responses against viruses. These cells are responsible for detecting pathogen-associated molecular patterns, thereby initiating a signaling cascade that results in the production of cytokines such as interferons to mitigate infections. The aim of this review is to outline recent advances in our knowledge of the roles that neutrophils and inflammatory monocytes play in initiating and coordinating host responses against viral infections. A focus is placed on myeloid cell development, trafficking and antiviral mechanisms. Although known for promoting inflammation, there is a growing body of literature which demonstrates that myeloid cells can also play critical regulatory or immunosuppressive roles, especially following the elimination of viruses. Additionally, the ability of myeloid cells to control other innate and adaptive leukocytes during viral infections situates these cells as key, yet under-appreciated mediators of pathogenic inflammation that can sometimes trigger cytokine storms. The information presented here should assist researchers in integrating myeloid cell biology into the design of novel and more effective virus-targeted therapies.
Output: viruses Myeloid Cells during Viral Infections and Inflammation
Post-translational protein modification is an important strategy for the regulation of the cell proteome independent of the need for new gene expression. Ubiquitin and ubiquitin-like modifiers mediate the regulation of protein levels, signaling pathways, vesicular trafficking, and many other cellular processes through their covalent conjugation to proteins. Interferon stimulated gene 15 (ISG15) is a type I interferon induced ubiquitin-like modifier. In addition to conjugating to potentially hundreds of target proteins, ISG15 can be found in an unconjugated form both inside of the cell and released from interferon stimulated cells into the extracellular environment. Due to its robust expression after type I interferon stimulation and the broad panel of proteins that it targets, ISG15 has drawn much attention as a potential regulator of the immune response and has been shown to mediate protection in a number of different viral infection models. Here we will review the current state of the field of ISG15, the viruses against which ISG15 mediates protection, and the mechanisms by which ISG15 exerts antiviral activity.
Output: The antiviral activities of ISG15
The coronavirus disease 2019 has grown up to be a pandemic within a short span of time. To investigate transmission dynamics and then determine control methodology, we took epidemic in Wuhan as a study case. Unfortunately, to our best knowledge, the existing models are based on the common assumption that the total population follows a homogeneous spatial distribution, which is not the case for the prevalence occurred both in the community and in hospital due to the difference in the contact rate. To solve this problem, we propose a novel epidemic model called SEIR-HC, which is a novel epidemic model with two different social circles. Using the model alongside the exclusive optimization algorithm, the spread process of COVID-19 epidemic in Wuhan city is reproduced and then the propagation characteristics and unknown data are estimated. Furthermore, the control measures implemented in Wuhan are assessed and the control methodology of COVID-19 is discussed to provide guidance for limiting the epidemic spread.
Output: Transmission Dynamics and Control Methodology of COVID-19: a Modeling Study
Feline infectious peritonitis (FIP) is the most frequent lethal infectious disease in cats. However, understanding of FIP pathogenesis is still incomplete. Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens from 28 cats that succumbed to FIP. Within one cat, viral sequences from different organs were similar or identical, whereas greater discrepancies were found comparing sequences from various cats. Eleven of the cats exhibited deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b gene was affected by deletions only in one cat. In three of the FIP cats, coronavirus isolates with both intact 3c genes as well as 7b genes of full length could also be detected. Thus, deletions or stop codons in the 3c sequence seem to be a frequent but not compelling feature of FIPVs.
Output: Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats
The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for anti-viral strategies, and the identification of viral cell receptor is critical for better understanding and controlling viral disease. As a model system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis virus (ASLV, including the A-J ten subgroups) has been studied intensively and many milestone discoveries have been achieved based on work with ASLV. Here, we used a DF1 cell line expressed viral receptor-binding protein to efficiently identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA to chANXA2 significantly inhibited ALV-J infection and replication, and over-expression of chANXA2 permitted the entry of ALV-J into its non-permissible cells. Our findings have not only identified chANXA2 as a novel biomarker for anti-ALV-J, but also demonstrated that cell lines with the expression of viral receptor-binding protein could be as efficient tools for isolating functional receptors to identify novel anti-viral targets.
Output: Identification of novel viral receptors with cell line expressing viral receptor-binding protein
Bronchopulmonary C-fi bers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human. CHEST 2014; 146 ( 6 ): 1633 -1648 ABBREVIATIONS : ATP 5 adenosine triphosphate ; GERD 5 gastroesophageal reflux disease ; GIT 5 gastrointestinal tract ; nTS 5 nucleus tractus solitarius ; RAR 5 rapidly adapting receptor ; SAR 5 slowly adapting receptor ; TRPA1 5 transient receptor potential A1 ; TRPM8 5 transient receptor potential M8 ; TRPV1 5 transient receptor potential vanilloid 1 [ Evidence-Based Medicine ]
Output: Anatomy and Neurophysiology of Cough CHEST Guideline and Expert Panel Report
Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.
Output: Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?
Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02-4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15-3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease.
Output: The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children
Multipartitism counts amongst the weirdest lifestyles found in the virosphere. Multipartite viruses have genomes segmented in pieces enclosed in different capsids that are independently transmitted. Since all segments have to meet in the host for complementation and completion of the viral cycle, multipartite viruses are bound to fight the loss of genomic information. While this is an obvious disadvantage of this strategy, no consensus on its actual advantages has been reached. In this review we present an exhaustive summary of all multipartite viruses described to date. Based on evidence, we discuss possible mechanistic and evolutionary origins of different groups, as well as their mutual relationships. We argue that the ubiquitous interactions of viruses with other unrelated viruses and with subviral elements might be regarded as a plausible first step towards multipartitism. In agreement with the view of the Virosphere as a deeply entangled network of gene sharing, we contend that the power of multipartitism relies on its dynamical and opportunistic nature, because it enables immediate adaptive responses to environmental changes. As such, perhaps the reasons for its success should be shought in multipartitism itself as an adaptive mechanism, to which its evolutionarily short-lived products (that is, the extant ensemble of multipartite viral species) are subordinated. We close by discussing how our understanding of multipartitism would improve by using concepts and tools from systems biology.
Output: Multipartite viruses: adaptive trick or evolutionary treat?
Most virus infections induce cycloxygenase-2 (COX-2) expression and subsequent prostaglandin E 2 (PGE 2 ) production in cells, an inflammatory response that might be detrimental to virus replication and pathogenesis. This response in dengue virus infection remains to be elucidated. Triptolide and tetrandrine, compounds derived from two commonly used Chinese herbs, both demonstrate anti-inflammatory and immunosuppressive effects partly through modulation of COX-2 expression and, hence, may have antiviral effects. In this study, we examined, firstly, the immune response to dengue virus infection with respect to COX-2 expression and PGE 2 production in human lung cells (A549), liver cells (HepG2) and dendritic cells. Secondly, we assessed the potential antiviral effects of triptolide and tetrandrine on dengue virus infection vis-à-vis expression of COX-2, PGE 2 , transcription factors, as well as virus production. We found that dengue virus infection enhanced COX-2 expression and PGE 2 production in A549 cells, similarly to the response in dendritic cells, but not in HepG2 cells. In dengue virus-infected A549 cells, nuclear factor κB (NF-κB) and activator protein 1 (AP-1) were also activated, and both were dose-dependently inhibited by triptolide (0.5-4 ng/ml). Tetrandrine (1-10 μM) had no similar immunosuppressive effects and, moreover, at higher concentrations, enhanced NF-κB and AP-1 activity, COX-2 expression and PGE 2 production. However, unexpectedly, tetrandrine, but not triptolide, dose-dependently suppressed dengue virus production in A549 cells, independent of PGE 2 level. Our findings imply that triptolide and tetrandrine may attenuate dengue virus infection in human lung cells, but through distinct pathways.
Output: Differential effects of triptolide and tetrandrine on activation of COX-2, NF-κB, and AP-1 and virus production in dengue virus-infected human lung cells
Backgrounds Since December 2019, a novel coronavirus epidemic has emerged in Wuhan city, China and then rapidly spread to other areas. As of 20 Feb 2020, a total of 2,055 medical staff confirmed with coronavirus disease 2019 (COVID-19) caused by SARS-Cov-2 in China had been reported. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff. In this retrospective study, 64 confirmed cases of novel coronavirus-infected medical staff admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 15 Feb, 2020 were included. Two groups concerned were extracted from the subjects based on duration of symptoms: group 1 (≤10 days) and group 2 (>10 days). Epidemiological and clinical data were analyzed and compared across groups. The Kaplan-Meier plot was used to inspect the change in hospital discharge rate. The Cox regression model was utilized to identify factors associated with hospital discharge. The median age of medical staff included was 35 years old. 64% were female and 67% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (5%) as well as patients in fever clinics (8%) and isolation wards (5%). Fever (67%) was the most common symptom, followed by cough (47%) and fatigue (34%). The median time interval between symptoms onset and admission was 8.5 days. On admission, 80% of medical staff showed abnormal IL-6 levels and 34% had lymphocytopenia. Chest CT mainly manifested as bilateral (61%), septal/subpleural (80%) and ground-glass (52%) opacities. During the study period, no patients was transferred to intensive care unit or died, and 34 (53%) had been discharged. Higher body mass index (BMI) (≥ 24 kg/m 2 ) (HR 0.14; 95% CI 0.03-0.73), fever (HR 0.24; 95% CI 0.09-0.60) and higher levels of IL-6 on admission (HR 0.31; 95% CI 0.11-0.87) were unfavorable factors for discharge. Interpretation In this study, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course, which may be partly due to their . CC-BY-NC-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 . https://doi.org/10.1101/2020.03.09.20033118 doi: medRxiv preprint medical expertise, younger age and less underlying diseases. Smaller BMI, absence of fever symptoms and normal IL-6 levels on admission are favorable for discharge for medical staff. Further studies should be devoted to identifying the exact patterns of SARS-CoV-2 infection among medical staff.
Output: Epidemiological, Clinical Characteristics and Outcome of Medical Staff Infected with COVID-19 in Wuhan, China: A Retrospective Case Series Analysis
Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year. For this reason, development of universal vaccines targeting conserved viral components is needed. In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses. We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K d -restricted NP 147-155 epitope than sublingual immunization. Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges. These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus.
Output: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection