Global epidemiology of Equine Influenza viruses: "A possible emerging zoonotic threat in future" an extensive systematic review with evidence / Epidemiologia global dos vírus da Gripe Equina: "Uma possível ameaça zoonótica emergente no futuro" uma extensa revisão sistemática com evidências

There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Existem diferentes opiniões em todo o mundo a respeito da capacidade zoonótica dos vírus da influenza equina H3N8. Neste relatório, tentamos resumir os resultados de diferentes pesquisas e artigos de revisão da literatura científica chinesa, inglesa e mongol relatando as evidências de infecções pelo vírus da influenza equina em seres humanos. Diferentes mecanismos de busca, como CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med e Web of Knowledge geraram 926 artigos, dos quais 32 atenderam aos critérios de inclusão para esta revisão. Analisando os dados epidemiológicos e filogenéticos desses artigos, encontramos uma considerável evidência experimental e observacional de vírus da influenza equina H3N8 infectando seres humanos em diferentes partes do mundo no passado. Artigos publicados recentemente no Paquistão e na China destacaram a ameaça emergente e a capacidade dos vírus da influenza equina para uma epidemia em seres humanos no futuro. Neste artigo de revisão, resumimos os relatórios científicos relevantes publicados sobre a epidemiologia dos vírus da influenza equina e seu aspecto zoonótico. Além disso, vários desenvolvimentos recentes no início do século 21, incluindo a transmissão e estabelecimento de vírus da influenza equina em diferentes espécies animais, ou seja, camelos e cães, e presumida encefalopatia associada aos vírus da influenza em cavalos, documentaram a natureza imprevisível dos vírus da influenza equina. Em suma, vários relatórios destacaram a natureza imprevisível de H3N8 EIVs destacando a necessidade de vigilância contínua para H3N8 em equinos e humanos em contato com eles para novas mutações ameaçadoras.

Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Infectious diseases dynamics in growing/finishing pigs in Southern Brazil (2005-2016) / Dinâmica de ocorrência das doenças infecciosas em suínos nas fases de crescimento e terminação no sul do Brasil (2005-2016)

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)

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice / 生物医学与环境科学（英文）

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.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

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.

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

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.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

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.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

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.

Análisis de las Campañas de Vacunación Antigripal destinadas al personal de salud del HIBA: período 2016-2018 / Analysis of Influenza Vaccination Campaigns for HIBA health personnel: 2016-2018 period

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)

Conocimientos sobre enfermedades tipo influenza en estudiantes de Medicina de la Universidad de Guayaquil, Ecuador / Knowledge about influenza-like illnesses in medical students at Guayaquil University, Ecuador

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.

Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice / 中国天然药物

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.

Evolution of equine influenza viruses (H3N8) during a Brazilian outbreak, 2015

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.

Innate and adaptive T cells in influenza disease / 医学前沿

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.

Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus / 中国中药杂志

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.

Swine-spread severe influenza-associated pneumonia: A case report and literature review / 中南大学学报(医学版)

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.

Detección serológica de Brucella suis, virus de influenza y virus de la enfermedad de Aujeszky en criaderos porcinos familiares de menos de 100 madres en Argentina / Serological detection of Brucella suis, influenza virus and Aujeszky's disease virus in backyard and small swine holders in Argentina

Los criaderos porcinos de menos de 100 madres representan más del 99% de los de todo el país; sin embargo, existen escasos reportes sobre su situación sanitaria y productiva. Se recabó información productiva y se tomaron muestras para detectar anticuerpos contra Brucella suis (Bs), virus de la enfermedad de Aujeszky (VA) y virus de influenza (VI) en 68 establecimientos de menos de 100 madres ubicados en la región norte, centro y sur del país. El 80% de los establecimientos fueron positivos al VI H1 pandémico 2009, el 11% al H3 clúster 2, mientras que el 11,7% presentó anticuerpos contra el VA y el 6% contra Bs. Ninguno de los productores conocía los factores de riesgo para la transmisión de enfermedades del cerdo al humano. El 47% compra sus reproductores a pares o en ferias. En lo que respecta a normas de bioseguridad, solo el 16% de los establecimientos tenía cerco perimetral y el 37% de las granjas contaba con asesoramiento veterinario. Los resultados de este estudio demuestran que la caracterización productiva y el relevamiento sanitario son de suma importancia para mejorar la productividad y reducir el riesgo de transmisión de enfermedades. El conocimiento de la situación sanitaria y de los factores de riesgo es necesario para conseguir un mejor control y la erradicación de enfermedades en sistemas de baja tecnificación. Se deberían llevar a cabo estudios más representativos a nivel país para detectar los agentes circulantes y, sobre la base de esta información, implementar medidas de prevención y control.

Farmers raising less than 100 sows represent more than 99% of swine producers in Argentina, although little is known about their sanitary status and productive characteristics in the country. Sanitary and productive information was obtained. Furthermore, samples for serological studies were taken to detect antibodies against Brucella suis (Bs), Aujeszky's disease virus (AV) and influenza virus (IV) in 68 backyard and small producers with less than 100 sows located in the north, central and south regions of Argentina. Antibodies against H1 pandemic were detected in 80% of the farms while 11%, 11.7% and 6.0% of the producers were positive to influenza H3 cluster 2, AV and Bs, respectively. None of the producers was aware of the risk factors concerning the transmission of diseases from pigs to humans. A percentage of 47% of them buy pigs for breeding from other farmers and markets. With regard to biosecurity measures, only 16% of the farms had perimeter fences. The results of this study demonstrate that productive characterization and disease surveys are important to improve productivity and to reduce the risk of disease transmission among animals and humans. The study of sanitary status and risk factors is necessary for better control and eradication of diseases in backyard or small producers. More representative studies at country level should be carried out to detect the pathogensthat circulate and, with this knowledge, to implement prevention and control measures.

Incidence of influenza virus-associated severe acute respiratory infection in Damanhour district, Egypt, 2013

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

Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus

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.

A novel M2e-multiple antigenic peptide providing heterologous protection in mice

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.

Expression and adjuvant effects of the fusion peptide TBP5 / 生物工程学报

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.