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1.
Pesqui. vet. bras ; 40(4): 254-260, Apr. 2020. graf
Article in English | ID: biblio-1135617

ABSTRACT

This study aimed to determine the frequency and distribution of infectious diseases diagnosed through necropsy examination and histopathological analysis in growing/finishing pigs along 12 years (2005-2016) in Southern Brazil. We evaluated 1906 anatomopathological exams of pigs at growing/finishing phases, of which the infectious diseases corresponded to 75.6% of the cases (1,441/1,906). Porcine circovirus type 2 (PCV2) infections were the most frequent, accounting for 51.3% of the cases (739/1,441) with a higher frequency from 2005 to 2007, characterizing an epidemic distribution, with a gradual decline after 2008. Infectious diseases affecting the respiratory system were the second major cause with 30.1% of the cases. Among these, necrotizing bronchiolitis caused by swine Influenza (15.1%, 218/1,441) and bacterial pneumonia (15%, 216/1,441) were the main conditions. Influenza was mostly diagnosed from 2010 to 2013, accounting for 43.1% (167/387) of the cases. After this period, both respiratory infectious diseases were endemic. Digestive system infectious diseases accounted for 10.5% of the diagnoses (151/1,441), with the following main conditions: Salmonella spp. enterocolitis (43.7%, 66/151), Lawsonia spp. proliferative enteropathy (41.7%, 63/151), and Brachyspira spp. colitis (14.6%, 22/151). The latter had a higher incidence from 2012 to 2014 with all cases detected in this period. Polyserositis and bacterial meningitis represented, respectively, 5.8% (84/1,441) and 2.3% (33/1,441) of the cases diagnosed, with a constant endemic character.(AU)


O objetivo deste estudo consistiu em determinar a frequência e a distribuição das doenças infecciosas diagnosticadas através de exame de necropsia e análise histopatológica em suínos nas fases de crescimento/terminação ao longo de 12 anos (2005-2016) no sul do Brasil. Foram avaliados 1906 laudos anatomopatológicos de suínos nas fases de crescimento/terminação, dos quais as doenças infecciosas corresponderam a 75,6% (1441/1906) do total. As infecções por circovírus suíno tipo 2 (PCV2) foram as mais frequentes, contabilizando 51,3% (739/1441) dos casos, com uma alta frequência de 2005 a 2007 caracterizando uma distribuição epidêmica neste período, e um declínio gradual após o ano de 2008. A segunda principal causa incluiu as doenças infecciosas que afetam o sistema respiratório (30,1% dos casos). Dentre essas, destacaram-se a influenza suína (15,1%; 218/1441) e pneumonias bacterianas (15%; 216/1441). O diagnóstico de influenza apresentou uma frequência elevada de 2010 a 2013, totalizando 43,1% (167/387) dos casos. Após este período, ambas doenças infecciosas respiratórias exibiram caráter endêmico. As doenças infecciosas do sistema digestório totalizaram 10,5% (151/1441) dos diagnósticos, com as seguintes principais condições: enterocolite por Salmonella spp. (43,7%; 66/151), enteropatia proliferativa por Lawsonia spp. (41,7%; 63/151) e colite por Brachyspira spp. (14,6%; 22/151). A colite por Brachyspira spp. apresentou uma alta incidência de 2012 a 2014 com todos os casos detectados no período. As polisserosites e meningites bacterianas representaram 5,8% (84/1441) e 2,3% (33/1441) dos casos diagnosticados, respectivamente, com um caráter endêmico constante.(AU)


Subject(s)
Animals , Swine Diseases/epidemiology , Communicable Diseases/pathology , Communicable Diseases/epidemiology , Circovirus , Circoviridae Infections/pathology , Circoviridae Infections/epidemiology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/epidemiology , Influenzavirus A , Sus scrofa , Enterocolitis/epidemiology , Pneumonia of Swine, Mycoplasmal
2.
Article in English | WPRIM | ID: wpr-829012

ABSTRACT

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.


Subject(s)
Acute Disease , Animals , Disease Models, Animal , Female , Humans , Influenza, Human , Virology , Male , Membrane Proteins , Genetics , Metabolism , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections , Virology , Rodent Diseases , Virology
3.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828747

ABSTRACT

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.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Humans , Influenza A virus , Leflunomide , Pharmacology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
4.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828583

ABSTRACT

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.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Humans , Influenza A virus , Leflunomide , Pharmacology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
5.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-827018

ABSTRACT

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.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Humans , Influenza A virus , Leflunomide , Pharmacology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
6.
Protein & Cell ; (12): 894-914, 2020.
Article in English | WPRIM | ID: wpr-880885

ABSTRACT

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.


Subject(s)
A549 Cells , Animals , Apoptosis Regulatory Proteins/immunology , DEAD Box Protein 58/immunology , Dogs , HEK293 Cells , Humans , Influenza A Virus, H1N1 Subtype/immunology , Madin Darby Canine Kidney Cells , Mice , Mice, Knockout , Orthomyxoviridae Infections/pathology , Proteolysis , Signal Transduction/immunology , THP-1 Cells , TNF Receptor-Associated Factor 3/immunology , Ubiquitination/immunology , Viral Proteins/immunology
7.
Rev. Hosp. Ital. B. Aires (2004) ; 39(2): 43-50, jun. 2019. tab., graf.
Article in Spanish | LILACS | ID: biblio-1047853

ABSTRACT

Introducción: la vacunación antigripal es la forma más eficaz para prevenir la enfermedad por virus Influenza y sus complicaciones. La cobertura en los profesionales sanitarios es un indicador de calidad hospitalaria. Material y métodos: estudio descriptivo de corte transversal. A partir de registros vacunales, se calculó la cobertura para las campañas 2013 a 2018. Se compararon las coberturas por trienios. Se describieron características generales de las campañas de 2016 a 2018. Resultados: en 2016 se alcanzó la mayor tasa del período (59,79%, IC 95%:58,75-60,81); en 2017, la menor (34,46%, IC 95%:33,48-35,46). La campaña 2018 obtuvo una cobertura de 54,90% (IC 95%: 53,88-55,92) y se inició más tempranamente que otras. Al comparar las tasas trienales del período se observó una diferencia de proporción de -1,3% (IC 95%: -2.84-0.24). Durante los tres últimos años, el personal vacunado correspondió mayormente al sexo femenino, a la Sede Central y tenía relación contractual directa. Las mayores coberturas específicas correspondieron a la sede de San Justo y a los profesionales de enfermería. El puesto ambulante fue el que aplicó más vacunas. Conclusión: si bien hubo variaciones en las coberturas alcanzadas a lo largo de los años, siendo la del año 2016 la más elevada y la del año 2017 la más baja, no se observaron diferencias estadísticamente significativas en las coberturas alcanzadas al comparar trienios. Resulta necesario continuar realizando intervenciones adaptadas al contexto local que permitan alcanzar los objetivos de cobertura esperados. Discusión: se reconocieron varios obstáculos para alcanzar las coberturas esperadas. La educación al personal de salud, la evaluación sistematizada de los ESAVI (Eventos supuestamente atribuibles a vacunación e inmunización) y la descripción de los elementos que facilitaron las coberturas específicas elevadas de algunas subpoblaciones podrían contribuir para mejorar los resultados. (AU)


Introduction: influenza vaccination is the most effective way to prevent influenza virus disease and its complications. Coverage in health professionals measurement is an indicator of hospital quality. Material and methods: descriptive cross-sectional study. From vaccination records, the coverage was calculated for the 2013 to 2018 campaigns. The coverage for three years was compared. General characteristics of the campaigns from 2016 to 2018 were described. Results: in 2016, the highest was achieved during the period (59.79%, IC 95%: 58.75 -60.81). In 2017, the lowest (34.46%, IC 95%: 33.48-35,46). The 2018 campaign achieved a coverage of 54.90% (IC 95%: 53.88-55.92) and started earlier than others. When comparing the triennial rates of the period, a difference of proportion of -1.3% was observed (IC 95%: -2.84-0.24). During the last three years, the vaccinated staff corresponded mostly to the female sex, to the headquarters and had a direct contractual relationship. The largest specific coverage corresponded to the San Justo headquarters and to nursing professionals. The ambulatory position was the post that applied the most vaccines. Conclusion: although there were variations in the coverage achieved over the years, with 2016 being the highest and 2017 being the lowest, there were no statistically significant differences in the coverage achieved when comparing trienniums. It is necessary to continue carrying out interventions adapted to the local context to achieve the expected coverage objectives. Discussion: several obstacles were recognized to reach the expected coverage. The education of health personnel, the systematic evaluation of the ESAVIs and the description of the elements that facilitated the high specific coverage of some subpopulations could contribute to improve the results. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Influenza Vaccines/administration & dosage , Orthomyxoviridae Infections/prevention & control , Vaccination Coverage/statistics & numerical data , Quality of Health Care/statistics & numerical data , Influenza Vaccines/adverse effects , Influenza Vaccines/supply & distribution , Sex Factors , Epidemiology, Descriptive , Age Factors , Health Personnel/education , Health Personnel/statistics & numerical data , Immunization Programs/supply & distribution , Immunization Programs/statistics & numerical data , Orthomyxoviridae Infections/complications , Absenteeism , Vaccination Coverage/organization & administration
8.
Edumecentro ; 11(2): 5-18, abr.-jun. 2019. tab
Article in Spanish | LILACS | ID: biblio-1001882

ABSTRACT

RESUMEN Fundamento: las enfermedades tipo influenza son de fácil contagio y sus vías de transmisión difíciles de controlar si no son tratadas adecuadamente. Objetivo: determinar los conocimientos que poseen los estudiantes de pregrado y posgrado de la Facultad de Ciencias Médicas de la Universidad de Guayaquil sobre las enfermedades tipo influenza. Métodos: se realizó un estudio descriptivo transversal durante el mes de febrero de 2018. Se utilizaron métodos teóricos: análisis-síntesis e inducción-deducción, y empíricos: la encuesta en forma de cuestionario para indagar sobre el conocimiento de los estudiantes sobre la influenza. Resultados: la totalidad de ellos refirió poseer conocimientos sobre el tema. El 96,32 % de los de pregrado identificaron como más frecuentes la transmisión de tipo viral y el contagio por contacto con persona enferma; mientras en posgrado el 100 % expresó conocimientos al respecto; la complicación habitual más señalada fue la automedicación referida por el 72 % en pregrado y en el posgrado por el 57 %. En relación con las medidas preventivas, manifestaron conocerlas el 87 % y 89 % en el pregrado y posgrado respectivamente. Conclusiones: se comprobó que el grado de conocimientos sobre las enfermedades tipo influenza en cuanto a transmisión, etiología, acciones de protección y medidas preventivas en estos estudiantes de la Facultad de Ciencias Médicas de la Universidad de Guayaquil es aceptable, pero aún persisten algunas carencias identificadas en el estudio realizado.


ABSTRACT Background: influenza is an easily transmitted disease and its way of transmission is difficult to control if it is not properly treated. Objective: to determine the knowledge undergraduate and graduate students have on influenza-like disease at Guayaquil University Medical Sciences Faculty. Methods: a cross-sectional descriptive study was carried out at Guayaquil University Medical Sciences Faculty, during the month of February 2018. Theoretical methods were used: analysis-synthesis and induction-deduction, and empirical methods: the survey in the form of a questionnaire to inquire about students' knowledge on influenza. Results: all the students reported having knowledge on influenza. 96,32 % of the undergraduates identified the transmission of viral type by contact with the sick person as more frequent; in postgraduate studies 100 % expressed knowledge in this regard; the most common complication was self-medication referred by 72 % of undergraduate students in 72 % and in postgraduate students by 57 %. In relation to preventive measures, 87 % and 89 % expressed knowledge in undergraduate and postgraduate respectively. Conclusions: it was found that the degree of knowledge on the influenza-like disease in terms of transmission, etiology, protective actions and preventive measures in these students at Guayaquil University Medical Sciences Faculty is acceptable. There are still some shortcomings identified in the study carried out.


Subject(s)
Orthomyxoviridae , Students, Medical , Orthomyxoviridae Infections , Education, Medical
9.
Article in English | WPRIM | ID: wpr-776894

ABSTRACT

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.


Subject(s)
Animals , Cytokines , Metabolism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Gastrointestinal Microbiome , Houttuynia , Chemistry , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Inflammation , Drug Therapy , Pathology , Influenza A Virus, H1N1 Subtype , Virulence , Intestinal Mucosa , Metabolism , Microbiology , Pathology , Lung , Metabolism , Pathology , Male , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Pathology , Plant Extracts , Chemistry , Polysaccharides , Chemistry , Pharmacology , Therapeutic Uses , Toll-Like Receptors , Metabolism , Zonula Occludens-1 Protein , Metabolism
10.
Braz. j. microbiol ; 49(2): 336-346, Apr.-June 2018. tab, graf
Article in English | LILACS | ID: biblio-889223

ABSTRACT

Abstract Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain. The hemagglutinin amino acid sequences had nine substitutions, compared with the vaccine strain. Two of them were in antigenic site A (A138S and G142R), one in antigenic site E (R62K) and another not in antigenic site (K304E). The four substitutions changed the hydrophobicity of hemagglutinin. Three distinct genetic variants were identified during the outbreak. Eleven variants were found in four quasispecies, which suggests the equine influenza virus evolved during the outbreak. The use of an out of date vaccine strain or updated vaccines without the production of protective antibody titers might be the major contributing factors on virus dissemination during this outbreak.


Subject(s)
Animals , Genetic Variation , Disease Outbreaks , Orthomyxoviridae Infections/veterinary , Evolution, Molecular , Influenza A Virus, H3N8 Subtype/isolation & purification , Horse Diseases/epidemiology , Horse Diseases/virology , Orthomyxoviridae , Viral Proteins/genetics , Brazil/epidemiology , Sequence Analysis, DNA , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Amino Acid Substitution , Influenza A Virus, H3N8 Subtype/classification , Influenza A Virus, H3N8 Subtype/genetics , Genotype , Horses , Hospitals, Animal , Neuraminidase/genetics
11.
Article in Chinese | WPRIM | ID: wpr-813105

ABSTRACT

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.


Subject(s)
Animals , Humans , Influenza B virus , Influenza, Human , Virology , Lung , Virology , Male , Middle Aged , Orthomyxoviridae Infections , Pneumonia , Swine , Swine Diseases , Virology
12.
Frontiers of Medicine ; (4): 34-47, 2018.
Article in English | WPRIM | ID: wpr-772730

ABSTRACT

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, γδ cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8 and CD4 T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.


Subject(s)
Adaptive Immunity , Animals , Cross Protection , Humans , Immunity, Innate , Influenza Vaccines , Therapeutic Uses , Influenza, Human , Allergy and Immunology , Orthomyxoviridae , Allergy and Immunology , Orthomyxoviridae Infections , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology , Vaccination
13.
Article in Chinese | WPRIM | ID: wpr-771700

ABSTRACT

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus , the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods, and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER), median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4, TLR7, MyD88 and TRAF6 in MDCK cells at 24, 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92,1.59 g·L⁻¹ respectively, the TI values were 12.53, 38.78 respectively, and when the concentration of Mahuang Tang was 5.00 g·L⁻¹, ER values were 50.21%, 98.41% respectively, showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile, as compared with the virus group, the virus load was significantly inhibited in Mahuang Tang groups, and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4, TLR7,MyD88 and TRAF6 at 24, 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Dogs , Drugs, Chinese Herbal , Pharmacology , Influenza A Virus, H1N1 Subtype , Physiology , Madin Darby Canine Kidney Cells , Orthomyxoviridae Infections , Toll-Like Receptor 4 , Metabolism , Toll-Like Receptor 7 , Metabolism , Virus Replication
14.
EMHJ-Eastern Mediterranean Health Journal. 2016; 22 (7): 499-508
in English | IMEMR | ID: emr-181507

ABSTRACT

The epidemiology, seasonality and risk factors for influenza virus infection remains poorly defined in countries such as Egypt. Between 1 January and 31 December 2013, we used surveillance data on patients hospitalized with severe acute respiratory infection in three Egyptian government hospitals in Damanhour district to estimate the incidence rate of laboratory-confirmed seasonal influenza. Samples were taken from 1727 of 1856 patients; of these, 19% were influenza virus positive. The overall incidence of influenza virus-associated SARI during the study period was estimated to be 44 cases per 100 000 person-years [95% CI: 39-48]. The highest incidence of 166 cases per 100 000 person year [95% CI: 125-220] was observed in children aged 2 to 4 years. The incidence of influenza-virus associated SARI cases in pregnant women was estimated to be 17.3 cases per 100 000 person-years [95% CI: 6-54]. Majority of influenza virus-associated SARI occurred in autumn and early winter, and influenza A[H3N2] virus predominated. This was the first ever description of the epidemiology of seasonal influenza in Egypt. However, additional works are needed for greater understanding of influenza burden in Egypt


Subject(s)
Humans , Female , Male , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Orthomyxoviridae Infections/epidemiology , Respiratory Tract Infections/physiopathology , Pregnant Women , Orthomyxoviridae/pathogenicity
15.
Article in English | WPRIM | ID: wpr-110763

ABSTRACT

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.


Subject(s)
Animals , Antibodies, Viral/blood , Antigens, Viral/genetics , Body Weight , Cross Protection/immunology , Disease Models, Animal , Epitopes, T-Lymphocyte/genetics , Female , Influenza A Virus, H3N2 Subtype/genetics , Influenza Vaccines/immunology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Peptides/genetics , Random Allocation , Survival Analysis , Vaccines, Synthetic/immunology , Virus Replication
16.
Protein & Cell ; (12): 28-45, 2016.
Article in English | WPRIM | ID: wpr-757199

ABSTRACT

Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion.


Subject(s)
Animals , Cattle , Dogs , Hemagglutinins, Viral , Chemistry , Metabolism , Influenzavirus C , Physiology , Orthomyxoviridae Infections , Metabolism , Virology , Protein Conformation , Protein Folding , Protein Processing, Post-Translational , Viral Fusion Proteins , Chemistry , Metabolism
17.
Chinese Journal of Biotechnology ; (12): 648-658, 2015.
Article in Chinese | WPRIM | ID: wpr-240612

ABSTRACT

Thymopentin (TP5) and bursopentin (BP5) are both immunopotentiators. To explore whether the TP5-BP5 fusion peptide (TBP5) has adjuvant activity or not, we cloned the TBP5 gene and confirmed that the TBP5 gene in a recombinant prokaryotic expression plasmid was successfully expressed in Escherichia coli BL21. TBP5 significantly promoted the proliferation of thymic and splenic lymphocytes of mice. The potential adjuvant activity of the TBP5 was examined in mice by coinjecting TBP5 and H9N2 avian influenza virus (AIV) inactivated vaccine. HI antibody titers, HA antibodies and cytokines levels (IL-4 and IFN-γ) were determined. We found that TBP5 markedly elevated serum HI titers and HA antibody levels, induced the secretion of both IL-4 and IFN-γ cytokines. Furthermore, virus challenge experiments confirmed that TBP5 contributed to inhibition replication of the virus [H9N2 AIV (A/chicken/Jiangsu/NJ07/05)] from mouse lungs. Altogether, these findings suggest that TBP5 may be an effective adjuvant for avian vaccine and that this study provides a reference for further research on new vaccine adjuvants.


Subject(s)
Adjuvants, Immunologic , Pharmacology , Animals , Antibodies, Viral , Blood , Cell Proliferation , Influenza A Virus, H9N2 Subtype , Physiology , Influenza Vaccines , Allergy and Immunology , Interferon-gamma , Allergy and Immunology , Interleukin-4 , Allergy and Immunology , Lymphocytes , Mice , Oligopeptides , Allergy and Immunology , Orthomyxoviridae Infections , Drug Therapy , Recombinant Fusion Proteins , Allergy and Immunology , Spleen , Cell Biology , Thymopentin , Allergy and Immunology , Thymus Gland , Cell Biology , Vaccines, Inactivated , Allergy and Immunology , Virus Replication
18.
Acta Pharmaceutica Sinica ; (12): 966-972, 2015.
Article in Chinese | WPRIM | ID: wpr-257040

ABSTRACT

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Glycyrrhizic Acid , Pharmacology , Inflammation , Allergy and Immunology , Influenza A Virus, H1N1 Subtype , Interleukin-1beta , Allergy and Immunology , Interleukin-6 , Allergy and Immunology , Lung , Allergy and Immunology , Virology , Mice , Orthomyxoviridae Infections , Drug Therapy , Pneumonia, Viral , Drug Therapy , Ribavirin , Pharmacology , Tumor Necrosis Factor-alpha , Allergy and Immunology
19.
Article in English | WPRIM | ID: wpr-310865

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the preventive effects of Qiangzhi Decoction (, QZD) on influenza A pneumonia through inhibition of inflammatory cytokine storm in vivo and in vitro.</p><p><b>METHODS</b>One hundred ICR mice were randomly divided into the virus control, the Tamiflu control and the QZD high-, medium-, and low-dose groups. Mice were infected intranasally with influenza virus (H1N1) at 10 median lethal dose (LD50). QZD and Tamiflu were administered intragastrically twice daily from day 0 to day 7 after infection. The virus control group was treated with distilled water alone under the same condition. The number of surviving mice was recorded daily for 14 days after viral infection. The histological damage and viral replication and the expression of inflammatory cytokines were monitored. Additionally, the suppression capacity on the secretion of regulated on activation normal T cells expressed and secreted (RANTES) and tumor necrosis factor-α (TNF-α) in epithelial and macrophage cell-lines were evaluated.</p><p><b>RESULTS</b>Compared with the virus control group, the survival rate of the QZD groups significantly improved in a dose-dependent manner (P<0.05), the viral titers in lung tissue was inhibited (P<0.05), and the production of inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), TNF-α, and intercellular adhesion molecule-1 (ICAM-1) were suppressed (P<0.05). Meanwhile, the secretion of RANTETS and TNF-α by epithelial and macrophage cell-lines was inhibited with the treatment of QZD respectively in vitro (p<0.05) CONCLUSIONS: The preventive effects of QZD on influenza virus infection might be due to its unique cytokine inhibition mechanism. QZD may have significant therapeutic potential in combination with antiviral drugs.</p>


Subject(s)
Animals , Cell Line , Cell Survival , Chemokine CCL5 , Metabolism , Chemokines , Metabolism , Cytokines , Metabolism , Dogs , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Enzyme-Linked Immunosorbent Assay , Hemagglutination, Viral , Humans , Inflammation , Pathology , Influenza A Virus, H1N1 Subtype , Physiology , Influenza A Virus, H1N2 Subtype , Lung , Pathology , Madin Darby Canine Kidney Cells , Mice, Inbred ICR , Orthomyxoviridae Infections , Pathology , Pneumonia , Pathology , Protective Agents , Pharmacology , Therapeutic Uses , Survival Rate , Tumor Necrosis Factor-alpha , Pharmacology
20.
Chinese Journal of Virology ; (6): 357-362, 2015.
Article in Chinese | WPRIM | ID: wpr-296276

ABSTRACT

To explore the impact of the history of infection by the influenza A virus subtype H1N1 on secondary infection by the influenza A virus subtype H9N2, pigs non-infected and pre-infected with H1N1 were inoculated with H9N2 in parallel to compare nasal shedding and seroconversion patterns. Unlike pigs without a background of H1N1 infection, nasal shedding was not detected in pigs pre-infected with H1N1. Both groups generated antibodies against H9N2. However, levels of H1N1 antibodies in pigs pre-infected with H1N1 increased quickly and dramatically after challenge with H9N2. Cross-reaction was not observed between H1N1 antibodies and H9N2 viruses. These findings suggest that circulation of the H1N1 virus might be a barrier to the introduction and transmission of the avian H9N2 virus, thereby delaying its adaptation in pigs.


Subject(s)
Animals , Antibodies, Viral , Allergy and Immunology , Cross Reactions , Immune Sera , Allergy and Immunology , Influenza A Virus, H1N1 Subtype , Allergy and Immunology , Physiology , Influenza A Virus, H9N2 Subtype , Allergy and Immunology , Orthomyxoviridae Infections , Blood , Allergy and Immunology , Species Specificity , Swine , Allergy and Immunology , Virology
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