This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Influenza B virus (IBV) is more likely to cause complications than influenza A virus (IAV) and even causes higher disease burden than IAV in a certain season, but IBV has received less attention. In order to analyze the genetic evolution characteristics of the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018), we constructed genetic evolution trees and analyzed the homology and different amino acids of hemagglutinin and neuraminidase referring to the vaccine strains recommended by World Health Organization (WHO). We found that strain B/Guangxi-Jiangzhou/1352/2018 was free of interlineage reassortment and poorly matched with the vaccine strain B/Colorado/06/2017 of the same year. We also determined the median lethal dose (LD₅₀) and the pathogenicity of strain B/Guangxi-Jiangzhou/1352/2018 in mice. The results showed that the LD₅₀ was 10^5.9 TCID₅₀ (median tissue culture infective dose), the IBV titer in the lungs reached peak 1 d post infection and the mRNA level of the most of inflammatory cytokines in the lungs reached peak 12 h post infection. The alveoli in the lungs were severely damaged and a large number of inflammatory cells were infiltrated post infection. The study demonstrated that the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018) could infect mice and induce typical lung inflammation. This will facilitate the research on the pathogenesis and transmission mechanism of IBV, and provide an ideal animal model for evaluation of new vaccines, antiviral and anti-inflammatory drug.
Amino Acids/genetics* ; Animals ; Antiviral Agents/pharmacology* ; China ; Cytokines/metabolism* ; Hemagglutinins/metabolism* ; Humans ; Influenza B virus/pathogenicity* ; Influenza, Human/virology* ; Mice ; Neuraminidase/genetics* ; Orthomyxoviridae Infections/virology* ; Phylogeny ; RNA, Messenger/metabolism* ; Virulence/genetics*

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective: Interferon-induced transmembrane protein 3 (IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection . Methods: We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer (NK) cell numbers, their activation, and their immune function in the lungs of -/- and wild-type mice. Results: -/- mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of -/- mice during acute influenza infection. Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in -/- mice.
Acute Disease ; Animals ; Disease Models, Animal ; Female ; Humans ; Influenza, Human ; virology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections ; veterinary ; virology ; Rodent Diseases ; virology

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Birds ; virology ; Child ; Child, Preschool ; Global Warming ; Humans ; Infant ; Influenza A virus ; Influenza, Human ; epidemiology ; Middle Aged ; Orthomyxoviridae Infections ; epidemiology ; Temperature ; Young Adult

Mice models of viral pneumonia were induced by pulmonary adaptive strain FM1 of influenza A virus in Asian mice.RT-PCR and immunohistochemistry were used to dynamically observe the effect of Scutellariae Radix on the protein and gene expression of inflammatory cytokine in the lungs of the model mice infected by influenza virus FM1 at different phases. The partial mechanism of Scutellariae Radix in repairing the immune inflammatory damage of target organs of pneumonia caused by influenza virus was further explored. The results showed that Scutellariae Radix reduced protein and gene expression of proinflammatory cytokines tumor necrosis factor( TNF-α),interleukin IL-1,IL-6 in lung tissues from 3 rd to 5 th day after infection,and increased protein and gene expression of IL-10 and IFN-γ in lung tissues on the 5 th day after infection. Scutellariae Radix may inhibit excessive release of pro-inflammatory cytokines and promote the expression of anti-inflammatory cytokines,thereby inhibiting the systemic inflammatory response syndrome,reducing the immunoinflammatory pathological damage of lung caused by influenza virus FM1 infection,and promoting lung repair of tissue inflammatory lesions.
Animals ; Cytokines/immunology* ; Drugs, Chinese Herbal/therapeutic use* ; Lung/virology* ; Mice ; Orthomyxoviridae ; Orthomyxoviridae Infections/drug therapy* ; Pneumonia, Viral/drug therapy* ; Scutellaria baicalensis/chemistry*

Objective: To understand the epidemiological characteristics of influenza in Guangdong province, during the winter of 2017-2018, to provide evidence for response to the diversity of influenza, in different seasonal patterns. Methods: Data on weekly influenza surveillance from January 2016 to April 2018, were collected in Guangdong. Information on patients with Influenza-like illness (ILI), on influenza virus positive rates and on outbreaks during the winter of 2017 to 2018, was analyzed and compared with those in spring of 2016 and summer of 2017. χ(2) test and Fisher exact test were used. Results: In the above said winter, the average percentage of visits for ILI in 28 hospitals where sentinel surveillance program had been set, was 4.99% (157 235/3 149 656), which was above the level of the same period in the previous five years. The positive rates of influenza virus among samples collected from ILI outpatients and hospitalized cases under severe acute respiratory infection (SARI) were 28.33% (2 137/7 543) and 14.93% (256/1 715), with the proportions of B (Yamagata) as 70.43% (1 505/2 137) and 73.05% (187/256) respectively. A total of 257 influenza outbreaks were reported in the winter period, with 82.49% (212/257) occurred in elementary schools. Cases aged 6-14 years occurred in winter and spring appeared of having higher positive rate than those seen in summer (P<0.05) whereas elderly cases aged 60 and above showed higher positive rate in summer than those in winter and spring two seasons (P<0.05). Conclusions: Epidemiological characteristics of influenza appeared in Guangdong province, during the winter from 2017 to 2018, were correlated to Influenza B (Yamagata). Capacity on the implementation of surveillance programs and on the coverage of vaccination should be improved and increased in order to control influenza in different epidemic seasons, in Guangzhou.
Adolescent ; Adult ; Aged ; Child ; China/epidemiology* ; Disease Outbreaks ; Epidemics ; Humans ; Infant ; Influenza Vaccines/administration & dosage* ; Influenza, Human/virology* ; Middle Aged ; Orthomyxoviridae/isolation & purification* ; Population Surveillance ; Respiratory Tract Infections/epidemiology* ; Seasons ; Sentinel Surveillance ; Vaccination

We report and analyze the clinical data of the first case of severe pneumonia caused by influenza B virus from swine. The patient, a 62 year-old male domestic pig breeder, was admitted to hospital because of fever and muscle pain for 5 days, and anhelation for 3 days. One week before the onset of disease, the patient kept close contact with pigs. CT scan of the chest showed diffuse infiltration in both lungs. Influenza B virus antigen detection (colloidal gold method) was repeatedly positive. These all confirmed influenza B virus infection. Poor appetite, weight loss, cough, poor spirit of pigs, positive influenza B virus antigen test occurred in the pig, while the patient had no history of exposure to influenza B-infected patients. It was likely that influenza B virus was transmitted from domestic pigs to the patient by droplets or close contact. Influenza B virus epidemics always occur every five or six years a time, and patients and carriers are the main source of infection. After searching the Pubmed, Web of science, Elsevier, Wanfang, and CNKI databases, it was found that although there were many studies on influenza B virus infecting seals, ferret, domestic pigs, guinea pigs, and other animals, there was no case report for animal-to-human infection. It is the first case report of type B influenza virus transmission from domestic pigs to people in the world, which provides a new direction for the research and prevention of influenza B virus.
Animals ; Humans ; Influenza B virus ; Influenza, Human ; complications ; etiology ; virology ; Lung ; virology ; Male ; Middle Aged ; Orthomyxoviridae Infections ; transmission ; Pneumonia ; etiology ; Swine ; Swine Diseases ; transmission ; virology

Animals ; Humans ; Immunity, Innate ; immunology ; Influenza, Human ; immunology ; Interferons ; immunology ; Orthomyxoviridae Infections ; immunology ; virology

OBJECTIVETo investigate the distribution of respiratory viruses on throat swabs in hospitalized children with acute lower respiratory tract infection (ALRTI).

METHODSA total of 5,150 children with ALRTI who were admitted to Hebei Children's Hospital between March 2014 and February 2015 were enrolled to investigate the distribution of respiratory viruses in children with ALRTI. Direct immunofluorescence assay was performed for throat swabs from these children to detect influenza virus A (FA), influenza virus B (FB), adenovirus (ADV), respiratory syncytial virus (RSV), and parainfluenza virus types 1, 2, and 3 (PIV-1, PIV-2, and PIV-3).

RESULTSOf all the 5,150 throat swabs from hospitalized children, 2,155 (41.84%) had positive virus detection results. RSV had the highest detection rate (1,338 cases/25.98%), followed by PIV-3 (439 cases/8.52%) and FA (166 cases/3.22%), and 29 patients had mixed infection with 2 viruses. With the increasing age, the detection rates of viruses tended to decrease (χ2=279.623; P<0.01). The positive rate of RSV increased gradually from September, and reached the peak value (60.09%) in November; the lowest positive rate occurred in June (1.51%). The positive rate of PIV-3 was the highest in May (21.38%) and the lowest in November (1.77%).

CONCLUSIONSThe distribution of viruses in children with ALRTI varies with age and season, with RSV prevalence in autumn and winter and PIV-3 prevalence in spring and summer. RSV is the most common viral pathogen that causes ALRTI in hospitalized children.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Orthomyxoviridae ; isolation & purification ; Parainfluenza Virus 3, Human ; isolation & purification ; Respiratory Syncytial Viruses ; isolation & purification ; Respiratory Tract Infections ; virology ; Seasons