Antiviral opportunities of Mannich bases derived from triterpenic N-propargylated indoles.

Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH-group condensed with the triterpene A-ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin-Darby canine kidney (MDCK) cell culture and SARS-CoV-2 pseudovirus in baby hamster kidney-21-human angiotensin-converting enzyme 2 (BHK-21-hACE2) cells. Mannich bases of oleanolic and glycyrrhetic acids N-propargylated indoles 7, 8, and 12 were the most efficacious against influenza virus A with IC50 7-10 µM together with a low toxicity (CC50 > 145 µM) and high selectivity index SI value 20. Indolo-oleanolic acid morpholine amide Mannich base holding N-methylpiperazine moiety 9 showed anti-SARS-CoV-2 pseudovirus activity with EC50 value of 14.8 µM. Molecular docking and dynamics modeling investigated the binding mode of the compounds 7 and 12 into the binding pocket of influenza A virus M2 protein and compound 9 into the RBD domain of SARS-CoV-2 spike glycoprotein.

Therapeutic effectiveness of sinensetin against cancer and other human complications: A review of biological potential and pharmacological activities.

BACKGROUND: Plant and their active phytoproducts have been used in modern medicine and playing an important role in the health sectors since a very early age. Human beings need a considerable amount of these plant-based phytochemicals for their health. The flavonoidal class phytochemical is an important class of natural products in modern healthcare because of their different pharmacological activities and health benefits. Flavonoidal class phytochemicals have been used to treat diabetes and related secondary complications in humans. Flavonoids have anti-apoptotic, anti-hyperlipidemic, anti-inflammatory, and anti-oxidant potential in the health sectors. Sinensetin, also called 3',4',5,6,7-pentametoksiflavon is a colorless compound with a molecular weight 372.37g/mol and is found to be present in the Orthosiphon stamineus. METHODS: In the present investigation, we aim to collect scientific information on sinensetin and analyze it for its biological potential and therapeutic benefits against various types of disorders and complications. Medicinal importance and pharmacological activities data have been collected and analyzed in the present work for sinensetin through literature data analysis of different research works. Google Science Direct, PubMed, Scopus, and Google Scholar were mainly searched to collect the scientific information in the present work. The present work analyzed sinensetin's biological potential, pharmacological activities, and analytical aspects. RESULTS: Literature data analysis of different scientific research works revealed the biological potential of phytochemicals in medicine, including flavonoids. Sinensetin has anti-tumor, anti-inflammatory, anti-oxidant, anti-diabetic, and antibacterial activities through their testing in different in vitro and in vivo models. Sinensetin has physiological functions, including anti-oxidant, anti-inflammation, and anti-cancer potential in medicine. Scientific data analysis signified the biological importance of sinensetin against tumors, gastric cancer, colorectal cancer, breast cancer, diabetes, influenza H1N1 infection, obesity, inflammation, colitis, brain disorders, and microbial infections. Further biological potential of sinensetin on enzymes and angiogenesis has been analyzed in the present work. Sinensetin was isolated through different analytical and extraction techniques, including chromatographic techniques. CONCLUSION: Literature data analysis signified sinensetin's biological potential and pharmacological activities in medicine.

CRISPR/Cas13a combined with hybridization chain reaction for visual detection of influenza A (H1N1) virus.

This study provides proof of concept of a colorimetric biosensor for influenza H1N1 virus assay based on the CRISPR/Cas13a system and hybridization chain reaction (HCR). Target RNA of influenza H1N1 virus activated the trans-cleavage activity of Cas13a, which cleaved the special RNA sequence (-UUU-) of the probe, further initiating HCR to copiously generate G-rich DNA. Abundant G-quadruplex/hemin was formed in the presence of hemin, thus catalyzing a colorimetric reaction. The colorimetric biosensor exhibited a linear relationship from 10 pM to 100 nM. The detection limit was 0.152 pM. The biosensor specificity was excellent. This new and sensitive detection method for influenza virus is a promising rapid influenza diagnostic test.

Transcriptome Differences in Normal Human Bronchial Epithelial Cells in Response to Influenza A pdmH1N1 or H7N9 Virus Infection.

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus-host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.

Generation, characterization, and protective ability of mouse monoclonal antibodies against the HA of A (H1N1) influenza virus.

Influenza virus infections pose a continuous threat to human health. Although vaccines function as a preventive and protective tool, they may not be effective due to antigen drift or an inaccurate prediction of epidemic strains. Monoclonal antibodies (mAbs) have attracted wide attention as a promising therapeutic method for influenza virus infections. In this study, three hemagglutinin (HA)-specific mAbs, named 2A1, 2H4, and 2G2, respectively, were derived from mice immunized with the HA protein from A/Michigan/45/2015(H1N1). The isolated mAbs all displayed hemagglutination inhibition activity and the 2G2 mAb exhibited the strongest neutralization effect. Two amino acid mutations (A198E and G173E), recognized in the process of selection of mAb-resistant mutants, were located in antigenic site Sb and Ca1, respectively. In prophylactic experiments, all three mAbs could achieve 100% protection in mice infected with a lethal dose of A/Michigan/45/2015(H1N1). A dose of 1 mg/kg for 2H4 and 2G2 was sufficient to achieve a full protective effect. Therapeutic experiments showed that all three mAbs could protect mice from death if they received the mAb administration at 6 h postinfection, and 2G2 was still protective after 24 h. Our findings indicate that these three mAbs may have potential prevention and treatment value in an H1N1 epidemic, as well as in the study of antigen epitope recognition.

Endothelial Dysfunction through Oxidatively Generated Epigenetic Mark in Respiratory Viral Infections.

The bronchial vascular endothelial network plays important roles in pulmonary pathology during respiratory viral infections, including respiratory syncytial virus (RSV), influenza A(H1N1) and importantly SARS-Cov-2. All of these infections can be severe and even lethal in patients with underlying risk factors.A major obstacle in disease prevention is the lack of appropriate efficacious vaccine(s) due to continuous changes in the encoding capacity of the viral genome, exuberant responsiveness of the host immune system and lack of effective antiviral drugs. Current management of these severe respiratory viral infections is limited to supportive clinical care. The primary cause of morbidity and mortality is respiratory failure, partially due to endothelial pulmonary complications, including edema. The latter is induced by the loss of alveolar epithelium integrity and by pathological changes in the endothelial vascular network that regulates blood flow, blood fluidity, exchange of fluids, electrolytes, various macromolecules and responses to signals triggered by oxygenation, and controls trafficking of leukocyte immune cells. This overview outlines the latest understanding of the implications of pulmonary vascular endothelium involvement in respiratory distress syndrome secondary to viral infections. In addition, the roles of infection-induced cytokines, growth factors, and epigenetic reprogramming in endothelial permeability, as well as emerging treatment options to decrease disease burden, are discussed.

Intranasal administration of immunogenic poly-epitope from influenza H1N1 and H3N2 viruses adjuvanted with chitin and chitosan microparticles in BALB/c mice.

OBJECTIVES: Prevalence of influenza virus, creates the need to achieve an efficient vaccine against it. We examined whether the predicted antigenic epitopes of HA, NP, and M2 proteins of the influenza H1N1 and H3N2 viruses accompanied by chitin and chitosan biopolymers might be relevant to the induction of effective proper mucosal responses. MATERIALS AND METHODS: The construct was prepared using B and T cell predicted epitopes of HA, NP, and M2 proteins from the influenza H1N1 and H3N2 viruses by considering haplotype "d" as a dominant allele in the BALB/c mice. Intranasal immunization with purified LPS free recombinant protein together with chitin and chitosan microparticles as adjuvants was administered at an interval of 2 weeks in thirty-five BALB/c female mice which were divided into seven groups. Ten days after the last immunization, humoral and cellular immune responses were examined. RESULTS: Elevated systemic IgG2a, IgA, and mucosal IgA revealed a humoral response to the construct. An increase in the number of IFN-γ-producing cells in re-stimulation of splenocytes in the culture medium by poly-tope as well as rise in the concentrations of IL-6, IL-17, and TNF-α along with the regulatory response of IL-10, presented the capacity of the designed protein to provoke significant immune responses. The neutralization test ultimately confirmed the high efficacy of the protein in inhibiting the virus. CONCLUSION: The results support the fact that immunogenic poly-tope protein in the presence of chitin and chitosan microparticles as mucosal adjuvants is able to induce humoral and cell-mediated responses in BALB/c mice.

Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses.

Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity.

Case Report: Co-infection with SARS-CoV-2 and influenza H1N1 in a patient with acute respiratory distress syndrome and a pulmonary sarcoidosis.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been a global public health concern. Co-infection of SARS-CoV-2 and other respiratory syndrome has been rarely reported. We report coinfection of SARS-CoV-2 and 2009 H1N1 Influenza strain in a French patient with pneumonia leading to acute respiratory distress syndrome.  The patient also had a medical history of pulmonary sarcoidosis with a restrictive ventilatory syndrome, which would be a supplementary risk to develop a poor outcomes. This case highlights the possible coinfection of two severe SARS-CoV-2 and influenza H1N1 viruses, which presents a higher risk to extend the care duration. The overlapping clinical features of the two respiratory syndromes is a challenge, and awareness is required to recommend an early differential diagnosis.

Characteristics of hospitalised patients with influenza in 2015-2016 in northern Israel: three circulating strains and continued fear of 2009 A/H1N1.

This study aimed to characterise children and adults diagnosed with influenza who were admitted to three medical centres in northern Israel in the winter of 2015-2016, a unique season due to infection with three types of influenza strains: A/H1N1, A/non-H1N1 and B. Data were collected retrospectively from medical records. Influenza A/H1N1 infected mainly adults (61% vs. 16% in children, P < 0.001) while influenza B was the common type in children (54% vs. 28% in adults, P < 0.001). Adults (36% vs. 5% in children, P < 0.001) and patients infected with A/H1N1 had higher rates of pneumonia (34% vs. 16% and 14% in influenza B and A/non-H1N1, respectively, P = 0.002). Treatment with oseltamivir was prescribed to 90% of patients; adults had higher rates of treatment (96% vs. 84% in children, P = 0.002) as well as patients infected with A/H1N1 (96% vs. 86% in influenza B and A/non-H1N1, respectively, P = 0.04). Oseltamivir was given after a mean of 3.6 days of symptoms. Preferential infection of adults by A/H1N1 was evident in Israel in 2015-2016; pneumonia rates were higher in adults and in A/H1N1-infected patients. Oseltamivir was prescribed to most patients but especially to those infected with A/H1N1, and was given relatively late in the course of the disease.

Identification of novel inhibitor against endonuclease subunit of Influenza pH1N1 polymerase: A combined molecular docking, molecular dynamics, MMPBSA, QMMM and ADME studies to combat influenza A viruses.

The influenza H1N1 virus is the causative agent of the flu pandemic in the world. Due to the shortage of effective means of control, it is remained the serious threats to public and avian health. To battle the surge of viral outbreaks, new treatments are crucially needed. The viral RNA polymerase, which is responsible for transcription and replication of the RNA genome, is comprised of subunits PA, PB1 and PB2. PA has endonuclease activity and is a well known target for inhibitor and drug design. In the current study, we employed molecular docking, molecular dynamics (MD), MMPBSA, QMMM and ADME studies to find and propose an inhibitor among 11,873 structures against PA. Our molecular docking, MD, MMPBSA and QMMM studies showed that ZINC15340668 has ideal characteristics as a potent PA inhibitor, and can be used in experimental phase and further development. Also, ADME prediction demonstrated that all physico-chemical parameters are within the acceptable range defined for human use. Molecular mechanism based study revealed that upon inhibitor binding; the flexibility of PA backbone is increased. This observation demonstrates the plasticity of PA active site, and it should be noticed in drug design against PA Influenza A viruses. In the final phase of the study, the efficiency of our proposed hit was tested computationally against mutant drug resistant I38T_PA. Our results exhibited that the hit inhibits the I38T_PA in different manner with high potency.

High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults.

Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18-20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point. Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers. Conclusion:IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort. This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection. However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort. If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.

Pandemic influenza and subsequent risk of type 1 diabetes: a nationwide cohort study.

AIMS/HYPOTHESIS: Case reports have linked influenza infections to the development of type 1 diabetes. We investigated whether pandemic and seasonal influenza infections were associated with subsequent increased risk of type 1 diabetes. METHODS: In this population-based registry study, we linked individual-level data from national health registries for the entire Norwegian population under the age of 30 years for the years 2006-2014 (2.5 million individuals). Data were obtained from the National Registry (population data), the Norwegian Patient Registry (data on inpatient and outpatient specialist care), the Primary Care Database, the Norwegian Prescription Database and the Norwegian Surveillance System for Communicable Diseases. Pandemic influenza was defined as either a clinical influenza diagnosis during the main pandemic period or a laboratory-confirmed test. Seasonal influenza was defined by a clinical diagnosis of influenza between 2006 and 2014. We used Cox regression to estimate HRs for new-onset type 1 diabetes after an influenza infection, adjusted for year of birth, sex, place of birth and education. RESULTS: The adjusted HR for type 1 diabetes after pandemic influenza infection was 1.19 (95% CI 0.97, 1.46). In the subgroup with laboratory-confirmed influenza A (H1N1), influenza was associated with a twofold higher risk of subsequent type 1 diabetes before age 30 years (adjusted HR: 2.26, 95% CI 1.51, 3.38). CONCLUSIONS/INTERPRETATION: Overall, we could not demonstrate a clear association between clinically reported pandemic influenza infection and incident type 1 diabetes. However, we found a twofold excess of incident diabetes in the subgroup with laboratory-confirmed pandemic influenza A (H1N1).

Aptamer selection and application in multivalent binding-based electrical impedance detection of inactivated H1N1 virus.

The type A influenza viruses are the most virulent and variable human pathogens with epidemic or even pandemic threat. The development of sensitive, specific and safe field testing methods is in particular need and quite challenging. We report here the selection and practical utilization of the inactivated influenza virus-specific aptamers. The DNA aptamers against inactivated intact H1N1 virus particles were identified through the systematic evolution of ligands by exponential enrichment (SELEX) procedure. The discriminative aptamers and their truncated sequences showed selectively high affinity to inactive H1N1 virus and H3N2 virus with the Kd in the low nanomolar range and collective binding properties. The truncated sequences were first applied in a sandwich enzyme-linked oligonucleotide assay (ELONA) with a H1N1 detection limit (LOD, S/N = 3) of 0.3 ng/µL and then in an electrochemical impedance (EIS) aptasensor with more than 300 times improved LOD (0.9 pg/µL) and the excellent selectivity over other viruses (> 100 times). Therefore the developed aptasensors represent the safer, simpler, and possibly better virus-variation adaptable means of virus diagnostics.

Swine Flu: Knowledge, Attitude, and Practices Survey of Medical and Dental Students of Karachi.

Introduction Pakistan is extremely susceptible to an influenza outbreak, as it shares borders with the most affected countries, namely China and India. The medical and dental students come into direct contact with the affected population and should be aware of the risk factors and signs and symptoms pertaining to swine influenza virus (SIV). Hence, this survey was conducted to assess the knowledge, perceptions and self-care practices of the medical and dental students with regards to this pandemic. Methods A descriptive, cross-sectional study was conducted to evaluate the swine flu-related knowledge, attitudes and practices of the medical and dental students at various institutions in Karachi, Pakistan. We approached 613 students that were available on the dates of this survey, keeping a medical to dental student ratio of 75:25. All students from first to final year comprised of the study population, and no internists or medical personnel were included. The questionnaire was divided into three sections, namely knowledge, attitudes and, practices. All questions were based on a multiple choice format. The data were entered and interpreted using the IBM Statistical Package for the Social Sciences 23.0 (IBM Corp., Armonk, New York). Results The majority of the students were aware that the swine flu is a transmittable disease (n=485, 80.8%). Most students identified the signs and symptoms correctly; however, diarrhea (15.5%) and vomiting (32.2%) were the least correct answers (n=93, n=193 respectively). Most of the preventative measures were reported accurately by the participants. Despite this, only 15.5% students (n=93) reported the use of a facemask when suffering from fever, cough and a runny nose. Conclusion There is a dire need for the routine integration of the awareness and management programs in the medical and dental schools. There exists a gap between the policy and practice, and it is high time we bridge the divide. The students should also be vaccinated annually for influenza A.

Influenza A H1N1 virus infection among pregnant women in a tertiary hospital in Belgrade, Serbia.

INTRODUCTION: Pregnant women are at higher risk of developing severe influenza. Our aim was to analyze clinical course and risk factors for fatal outcome in pregnant women with influenza (H1N1) infection. METHODOLOGY: This retrospective study enrolled eleven pregnant women with confirmed Influenza A (H1N1) infection treated in the Clinic for Infectious and Tropical Diseases, Belgrade, Serbia in a 6-years period. RESULTS: The mean age of pregnant women was 28.9 ± 5.2 years, and mean gestational age was 23.1 ± 7.0 weeks. Nine (81.8%) pregnant women had pneumonia (six had interstitial and three had bacterial pneumonia). Pregnant women developed pneumonia more often than other women in the reproductive period, but without statistical significance (81.8% vs. 65.7%, p = 0.330, OR (95% CI) 2.35 (0.47-11.80)). Nine (81.8%) pregnant women recovered. None of them experienced preterm delivery or abortion. Two women (18.2%) died due to acute respiratory distress syndrome. In one of them fetal death occurred one day before she died. The other one was performed caesarean section three days before death. Her newborn and children of all recovered women were healthy at birth. Prolonged time to initiation of oseltamivir and higher body mass index were statistically significantly associated with fatal outcome (p = 0.002, and p = 0.007, respectively). Gestational week of pregnancy, the etiology of pneumonia and comorbidity were not found to be risk factors for death (p = 0.128, p = 0.499 and p = 1.000, respectively). CONCLUSION: Pregnant women with H1N1 infection are at higher risk of pneumonia and death than other women in the reproductive period. Early antiviral therapy reduces the risk of unfavorable outcome.

Limited awareness of animal influenza prevention and control among Dai Lue smallholder farmers in Southwest China.

Awareness of animal influenza and its prevention and control is important for ensuring livestock health, production and welfare. In China, a country stereotyped as a major source of emerging zoonotic infectious diseases, research on the public understanding of animal influenza is limited to the Han, the main ethnic group. The present qualitative study in Southwest China investigated awareness of animal influenza among the Dai, an ethnic minority. The participants (15 men and 10 women, ages 18-83) were smallholder farmers of pigs and poultry in rural areas of Jinghong, Xishuangbanna, Yunnan Province. A mixture of interviews and group discussions took place in homes and villages. The participants were asked about their knowledge of avian influenza (H7N9), swine influenza (H1N1), precautions taken to protect against influenza, procedures when animals were sick and perceived risk of animal influenza. The data were analysed following coding and thematic analysis. The findings demonstrated a limited understanding of animal health and welfare among participants. Specifically, they were largely unaware of animal influenza (H7N9, H1N1) including its causes, symptoms, prevention and treatment. The farmers were also uninformed of the risks they faced and unknowingly engaged in behaviours which increased direct or indirect exposure to infected animals, a risk factor for human infection. They also reported poor usage of veterinary services. In order to guarantee the health, welfare and production of their livestock, immediate action is needed to enable Dai smallholder farmers to prevent and respond to animal influenza effectively and timely.

Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs.

Although several studies have exploited the effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated the effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild-type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice to the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of granulocyte-macrophage colony-stimulating factor, IFN-γ, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine and support PB1-F2 as a virulence factor of influenza A virus in a strain- and host-dependent manner.

Clinical analysis of nephrotic syndrome combined with H1N1 influenza in 15 children / 临床儿科杂志

Objective To explore the clinical features of nephrotic syndrome combined with H1N1 influenza. Methods The clinical manifestations, laboratory and image examinations, treatment, and prognosis of nephrotic syndrome combined H1N1 influenza were retrospectively analyzed in 15 children with. Results All of 15 children with nephrotic syndrome met the diagnostic criteria of H1N1 influenza. The median age of all children was 4-year-8-month old (2-year-2-month to 6-year-9-month). All children were treated with hormone alone or combined with other immunosuppressive drugs. Three cases were severe and another 5 cases were critically ill. Four cases were complicated with recurrence of nephrotic syndrome, 2 of which suffered from acute renal insufficiency. All children were given oseltamivir as antiviral treatment at admission. Four cases took oseltamivir within 48 hours of onset and showed mild symptoms. Fourteen children with H1N1I influenza were cured, their urinary proteins were significantly decreased or converted to negative, and the median hospital stay was 8 days (1 to 25 days). One child died of acute necrotizing encephalopathy and brain herniation. Conclusions Children with nephrotic syndrome are susceptible to severe or critical H1N1 influenza infections. During the epidemic of H1N1 influenza, the clinical preventive measures should be taken in children with nephrotic syndrome.