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Influenza Virus (influenza + virus)
Kinds of Influenza Virus Terms modified by Influenza Virus Selected AbstractsRole of apoptosis and cytokines in influenza virus morbidityFEMS MICROBIOLOGY REVIEWS, Issue 4 2005Edward W.A. Brydon Abstract Influenza virus is a major human pathogen that causes epidemics and pandemics with increased morbidity and, especially in the elderly and those with pre-existing medical conditions, increased mortality. Influenza is characterised by respiratory symptoms and constitutional symptoms. Whilst knowledge of the mechanisms underlying host and tissue specificity has advanced considerably of late we still know relatively little about other aspects of influenza virus virulence. In this review, we will explore what is known about the role of apoptosis in respiratory epithelial cell damage and the role of cytokines in inflammation and constitutional symptoms with particular emphasis on the link between apoptosis, inflammation, fever and cytokine production. [source] Influenza virus assays based on virus-inducible reporter cell linesINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5 2009Yunsheng Li Background, Virus-inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus-induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus-inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5,- and 3,-untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus-inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Findings, Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose-dependent and highly specific for influenza A or influenza B viruses. Conclusions, These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers. [source] Broad-spectrum antiviral effect of Agrimonia pilosa extract on influenza virusesMICROBIOLOGY AND IMMUNOLOGY, Issue 1 2010Woo-Jin Shin ABSTRACT Influenza virus continues to emerge and re-emerge, posing new threats for humans. Here we tested various Korean medicinal plant extracts for potential antiviral activity against influenza viruses. Among them, an extract of Agrimonia pilosa was shown to be highly effective against all three subtypes of human influenza viruses including H1N1 and H3N2 influenza A subtypes and influenza B virus. The EC50 value against influenza A virus, as tested by the plaque reduction assay on MDCK cells, was 14,23 ,g/ml. The extract also exhibited a virucidal effect at a concentration of 160,570 ng/ml against influenza A and B viruses when the viruses were treated with the extract prior to plaque assay. In addition, when tested in embryonated chicken eggs the extract exhibited a strong inhibitory effect in ovo on the H9N2 avian influenza virus at a concentration of 280 ng/ml. Quantitative RT-PCR analysis data showed that the extract, to some degree, suppressed viral RNA synthesis in MDCK cells. HI and inhibition of neuraminidase were observed only at high concentrations of the extract. And yet, the extract's antiviral activity required direct contact between it and the virus, suggesting that its antiviral action is mediated by the viral membrane, but does not involve the two major surface antigens, HA and NA, of the virus. The broad-spectrum antiviral activity of Agrimonia pilosa extract on various subtypes of influenza viruses merits further investigation as it may provide a means of managing avian influenza infections in poultry farms and potential avian-human transmission. [source] Study of human metapneumovirus-associated lower respiratory tract infections in Egyptian adultsMICROBIOLOGY AND IMMUNOLOGY, Issue 11 2009Maysaa El Sayed Zaki ABSTRACT There is a deficiency in the data concerning the role of hMPV in lower respiratory tract infections in adults, and until now there has been no data available regarding the prevalence of hMPV in adults in our region. In the present study the association of hMPV with varieties of lower respiratory tract disorders in immunocompetent adult patients, either alone or with bacterial pathogens, has been highlighted. Eighty-eight patients were included in the study. They included 46 males and 42 females with an age range of 38,65 years. Patients presented with lower respiratory tract infections associated with acute exacerbation of asthma (67%), pneumonia (17%), and acute exacerbation of chronic obstructive lung diseases. Sputum and nasopharyngeal samples were obtained from the patients and subjected to a full microbiological study. In addition, detection of hMPV was performed by nested reverse transcriptase polymerase chain reaction. The pathogens isolated were Streptococcus pneumoniae 46.6%, Staphylococci aureus 35.2%, and human metapneumovirus 13.6%. Influenza virus and rhinovirus were each isolated from 4.5% of patients. Human metapneumovirus was associated with S. pneumoniae in 4.5% in studied patients, while in 9.1% it was the only pathogen found in those patients. The commonest clinical condition with significant association with human metapneumovirus was pneumonia. The clinical and laboratory studies demonstrated an association between lower respiratory tract infections in adults and hMPV either as sole pathogen or in association with Streptococcus pneumoniae. It was a common pathogen in community-acquired pneumonia. [source] Hyperthermia in utero due to maternal influenza is an environmental risk factor for schizophreniaCONGENITAL ANOMALIES, Issue 3 2007Marshall J. Edwards ABSTRACT A hypothesis is presented that the association between maternal influenza and other causes of fever during the second trimester of pregnancy and the subsequent development of schizophrenia in the child is due to the damage caused by hyperthermia to the developing amygdalohippocampal complex and associated structures in the fetal brain. Hyperthermia is a known cause of congenital defects of the central nervous system and other organs after sufficiently severe exposures during early organogenesis. The pathogenic mechanisms include death of actively dividing neuroblasts, disruption of cell migration and arborization and vascular damage. In experimental studies, hyperthermia during later stages of central nervous system development also caused damage to the developing brainstem that was associated with functional defects. This damage usually results in hypoplasia of the parts undergoing active development at the time of exposure. Recent studies have shown no evidence of direct invasion of the fetus by the influenza virus. Factors that might interact with hyperthermia include familial liability to schizophrenia, season of birth, maternal nutrition, severe stress and medications used to alleviate the symptoms of fevers. The time of the development of the fetal amygdalohippocampal complex and the changes found in its structure and associated areas of the brain are compatible with the known effects of hyperthermia. [source] Seeking a second opinion: uncertainty in disease ecologyECOLOGY LETTERS, Issue 6 2010Brett T. McClintock Ecology Letters (2010) 13: 659,674 Abstract Analytical methods accounting for imperfect detection are often used to facilitate reliable inference in population and community ecology. We contend that similar approaches are needed in disease ecology because these complicated systems are inherently difficult to observe without error. For example, wildlife disease studies often designate individuals, populations, or spatial units to states (e.g., susceptible, infected, post-infected), but the uncertainty associated with these state assignments remains largely ignored or unaccounted for. We demonstrate how recent developments incorporating observation error through repeated sampling extend quite naturally to hierarchical spatial models of disease effects, prevalence, and dynamics in natural systems. A highly pathogenic strain of avian influenza virus in migratory waterfowl and a pathogenic fungus recently implicated in the global loss of amphibian biodiversity are used as motivating examples. Both show that relatively simple modifications to study designs can greatly improve our understanding of complex spatio-temporal disease dynamics by rigorously accounting for uncertainty at each level of the hierarchy. [source] The pathology of bronchointerstitial pneumonia in young foals associated with the first outbreak of equine influenza in AustraliaEQUINE VETERINARY JOURNAL, Issue 3 2008J. C. PATTERSON-KANE Summary Objectives: The aim of this study was to describe post mortem lesions in EIV-infected foals. Methods: Post mortem examinations were conducted on 11 young foals (age 2,12 days) submitted to the Scone Veterinary Hospital, New South Wales, Australia over a 2-month period in 2007. The foals had presented with or developed fatal pneumonia, and were known or suspected to be EIV-positive. Equine influenza virus nucleic acid was detected in tissue specimens using an influenza A group reactive real-time reverse transcriptase PCR assay. Results: Grossly there was diffuse or extensive pulmonary consolidation. Histological changes included: bronchiolar and alveolar necrosis; neutrophilic infiltration; hyaline membrane formation; and hyperplasia and squamous metaplasia of airway epithelium. Tissues for 10 foals were EIV-positive, with a positive nasal swab from the remaining animal. Conclusions: This is the first detailed pathological description of bronchointerstitial pneumonia associated with EIV infection in young foals. It is also the first series of such cases in which a causative agent has consistently been detected. Potential relevance: Given the findings in this outbreak, and a previous outbreak in the UK in 1965 involving a similarly naive population, veterinary clinicians and pathologists should be aware that EIV can cause fatal bronchointerstitial pneumonia in young foals that do not have maternal immunity. The lesions did not differ from those previously reported in foals of various ages with bronchointerstitial pneumonia of other or undefined causes, indicating that this is most likely to be a stereotypical response to a variety of insults. Therefore, tissue specimens should be obtained from cases of pneumonia in young foals for virological and bacteriological testing. Reasons for performing study: The first outbreak of equine influenza virus (EIV) infection was confirmed in Australia in 2007. Some EIV-positive young foals died with broncho-interstitial pneumonia, a rare disease process in this age group that is often postulated to be caused by viral infection. [source] Fine antigenic variation within H5N1 influenza virus hemagglutinin's antigenic sites defined by yeast cell surface displayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Jian Li Abstract Fifteen strains of mAb specific for HA of the A/Hong Kong/482/97 (H5N1) influenza virus were generated. The HA antigenic sites of the human A/Hong Kong/482/97 (H5N1) influenza virus were defined by using yeast cell surface-displaying system and anti-H5 HA mAb. Evolution analysis of H5 HA identified residues that exhibit diversifying selection in the antigenic sites and demonstrated surprising differences between residue variation of H5 HA and H3 HA. A conserved neutralizing epitope in the H5 HA protein recognized by mAb H5M9 was found using viruses isolated from 1997,2006. Seven single amino acid substitutions were introduced into the HA antigenic sites, respectively, and the alteration of antigenicity was assessed. The structure obtained by homology-modeling and molecular dynamic methods showed that a subtle substitution at residue 124 propagates throughout its nearby loop (152,159). We discuss how the structural changes caused by point mutation might explain the altered antigenicity of the HA protein. The results demonstrate the existence of immunodominant positions in the H5 HA protein, alteration of these residues might improve the immunogenicity of vaccine strains. [source] Influenza A virus abrogates IFN-, response in respiratory epithelial cells by disruption of the Jak/Stat pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Kohsaku Uetani Abstract The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-, is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-, as evidenced by studies using anti-IFN-, Ab and IFN-,,/, mice. Thus, we hypothesized that IFN-, is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-,. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-, to detect IFN-,-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-,-induced up-regulation of HLA-DR, mRNA and the IFN-, induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1, upon IFN-, stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1,. Thus, influenza A virus subverts antiviral host defense mediated by IFN-, through effects on the intracellular signaling pathways. [source] IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Alice Abstract The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-, production by NK cells and T,lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8+ T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40,/,) or IL-18 (IL-18,/,) genes were infected with an influenza,A virus and the characteristics of the resultant epitope-specific CD8+ T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8+ T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-,, TNF-,, and IL-2 by epitope-specific CD8+ T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8+ T cells for the efficient clearance of influenza virus from the lungs of infected mice. [source] Functional impairment of cytotoxic T cells in the lung airways following respiratory virus infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2006Simone Vallbracht Abstract We investigated the differentiation phenotype and function of virus-specific and non-specific CTL that were recruited to the lung parenchyma and the bronchoalveolar space after respiratory virus infections. Soon after virus elimination, we observed functional impairment of CTL isolated from the airways in their ability to produce IFN-, and TNF-, and to lyse target cells. Impaired cytotoxicity was due to a reduced content of granzyme B and a reduced ability to mobilize lytic granules. This impairment in effector functions (a) was largely restricted to CTL in the lung airways, (b) affected both CTL specific for the infecting virus as well as those that were recruited non-specifically to the inflamed lung, (c) was independent of contact between CTL and their specific viral antigen, (d) was not restricted to terminally differentiated CTL but also affected resting memory CTL and (e) could be elicited by both respiratory syncytial virus and influenza virus and thus seemed to be largely independent of the infecting virus. These observations suggest that functional impairment of antiviral T cells in the lung is not the consequence of a viral escape strategy. It may rather result from the particular milieu in the bronchoalveolar space and reflect a host mechanism to prevent excessive pulmonary inflammation. [source] Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challengeEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2006Nathalie Etchart Abstract We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSV-specific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636118 [source] Genetic immunity and influenza pandemicsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2006Sergey N. Rumyantsev Abstract In addition to the great number of publications focused on the leading role of virus mutations and reassortment in the origin of pandemic influenza, general opinion emphasizes the victim side of the epidemic process. Based on the analysis and integration of relevant ecological, epidemiological, clinical, genetic and experimental data, the present article is focused on the evolution of ,virus , victim' ecological systems resulting in the formation of innate (i.e. genetic, constitutional) immunity in the involved species and populations. This kind of immunity functions today as the greatest natural barrier to the pandemic spread of influenza among humans and ecologically related kinds of animals. Global influenza pandemics can arise when the worldwide population contains at least a minimum number of people susceptible to a known or mutant influenza virus. Special attention is paid in this article to individual tests for the presence of this barrier, including the implications of specific findings for public health policy. Such tests could be based on in vitro observation of the action of relevant virus strains on primary cell cultures or on their cellular or molecular components extracted from individuals. The resources of the Human Genome Project should also be utilized. [source] Antibody response to influenza infection of mice: different patterns for glycoprotein and nucleocapsid antigensIMMUNOLOGY, Issue 4 2003Robert Sealy Summary Our previous studies of C57BL/6 mice intranasally infected with influenza virus (A/PR8) revealed a spike of virus-specific immunoglobulin A (IgA)-secreting antibody-forming cells (AFC) in the mediastinal lymph node (MLN) 7 days post-infection. Here we show that these AFC are directed only against viral glycoprotein, and not nucleocapsid antigens. The early IgA spike associates with a decline in glycoprotein-specific AFC during week 2 post-infection. In contrast to the glycoprotein-specific AFC, nucleocapsid-specific, IgA-secreting AFC develop gradually in the MLN and persist for more than 3 weeks post-infection. As peripheral lymph node reactions wane, the nucleocapsid-specific AFC appear as long-sustained populations in the bone marrow. Microanatomical examination of the respiratory tract in infected mice shows foci of infection established in the lung 2 days post-infection, from which virus spreads to infect the entire lining of the trachea by day 3. At this time, viral haemagglutinin can be seen within the MLN, probably on projections from infected dendritic cells. This feature disappears within a day, though viral antigen expression continues to spread throughout the respiratory tract. Total IgA- and IgG-secreting AFC appear histologically in large numbers during the first week post-infection, significantly preceding the appearance of germinal centres (revealed by peanut agglutinin staining in week 2). To explain these results, we suggest that the initial immunogenic encounter of B cells with viral antigens occurs about 3 days post-infection in the MLN, with antigens transported by dendritic cells from airway mucosa, the only site of viral replication. Viral glycoproteins expressed as integral membrane components on the surface of infected dendritic cells [probably in the absence of cognate T helper (Th) cells] promote members of expanding relevant B-cell clones to undergo an IgA switch and terminal local plasmacytoid differentiation. Anti-glycoprotein specificities are thus selectively depleted from progeny of activated B-cell clones which are channelled to participate in germinal centre formation (perhaps by cognate T helper cells when they become sufficiently frequent). One product of the germinal centre reaction is the long-sustained, bone marrow-resident population, which is accordingly rich in anti-nucleoprotein, but not anti-glycoprotein specificities. Of note, we find that AFC responses toward influenza virus and Sendai virus differ, even though viral replication is limited to the airway mucosa in each case. The response towards Sendai virus exhibits neither the early appearance of anti-glycoprotein AFC expressing IgA in draining lymph nodes, nor the subsequent relative deficit of this specificity from bone marrow AFC populations. [source] Letter to the Editor: Why is influenza virus more risky for pregnant women?INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5 2010Maria Grazia Cusi No abstract is available for this article. [source] Serologic survey of swine workers for exposure to H2N3 swine influenza AINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 3 2010Amanda Beaudoin Please cite this paper as: Beaudoin et al. (2010) Serologic survey of swine workers for exposure to H2N3 swine influenza A. Influenza and Other Respiratory Viruses 4(3), 163,170. Background, Of the 16 influenza A hemagglutinin (H) subtypes, only H1, H2 and H3 viruses have been shown to cause sustained human infection. Whereas H1 and H3 viruses currently circulate seasonally in humans, H2 viruses have not been identified in humans since 1968. In 2006, an H2N3 influenza virus was isolated from ill swine in the United States. Objective, To assess the potential for zoonotic influenza transmission, the current study looked for serologic evidence of H2 influenza infection among workers at two swine facilities, some exposed and some unexposed to H2N3-positive pigs. Methods, The sera were assessed for antibodies to swine H2 influenza and currently circulating seasonal human influenza A subtypes H1N1 and H3N2. Workers were interviewed to obtain details such as age, influenza vaccination history, experiences of influenza-like-illness, and use of personal protective equipment and hygiene when working with pigs. Exposure and risk factors for positive antibody titers were compared for exposed and unexposed individuals as well as for H2 antibody-positive and H2 antibody-negative individuals. Results, Blood was taken from 27 swine workers, of whom four had positive H2 antibody titers (,1:40). Three of the positive employees were born before 1968 and one had an unknown birth date. Only one of these workers had been exposed to H2N3-positive pigs, and he was born in 1949. Conclusions, These data do not support the hypothesis that swine workers were infected with the emergent swine H2N3 influenza A virus. [source] Phenotypic characteristics of novel swine-origin influenza A/California/07/2009 (H1N1) virusINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 1 2010Irina Kiseleva Background, The 2009 novel A(H1N1) virus appears to be of swine origin. This strain causing the current outbreaks is a new virus that has not been seen previously either in humans or animals. We have previously reported that viruses causing pandemics or large outbreaks were able to grow at a temperature above the normal physiological range (temperature resistance, non-ts phenotype), were found to be inhibitor resistant and restricted in replication at suboptimal temperature (sensitivity to grow at low temperature, non-ca phenotype). In this study, we performed phenotypic analysis of novel A(H1N1) virus to evaluate its pandemic potential and its suitability for use in developing a live attenuated influenza vaccine. Objectives, The goal of this study is to identify phenotypic properties of novel A(H1N1) influenza virus. Methods, A/California/07/2009 (H1N1) swine-origin influenza virus was studied in comparison with some influenza A viruses isolated in different years with respect to their ability to grow at non-permissive temperatures. We also analyzed its sensitivity to gamma-inhibitors of animal sera and its ability to agglutinate chicken, human and guinea pig erythrocytes. Results, Swine-origin A/California/07/2009 (H1N1) virus was found to be non-ts and inhibitor resistant and was not able to grow at 25°C (non-ca). We did not find any difference in the ability of the hemagglutinin of A/California/07/2009 (H1N1) virus to bind to erythrocytes of different origin. Conclusion, The novel swine-origin A(H1N1) virus displays a phenotype typical of the past pandemic and epidemic viruses. This finding suggests that this virus might be a good wild type parental prototype for live vaccine for potential use for controlling pandemic influenza. [source] An ex vivo swine tracheal organ culture for the study of influenza infectionINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 1 2010Sandro F. Nunes Background The threat posed by swine influenza viruses with potential to transmit from pig populations to other hosts, including humans, requires the development of new experimental systems to study different aspects of influenza infection. Ex vivo organ culture (EVOC) systems have been successfully used in the study of both human and animal respiratory pathogens. Objectives We aimed to develop an air interface EVOC using pig tracheas in the study of influenza infection demonstrating that tracheal explants can be effectively maintained in organ culture and support productive influenza infection. Methods Tracheal explants were maintained in the air interface EVOC system for 7 days. Histological characteristics were analysed with different staining protocols and co-ordinated ciliary movement on the epithelial surface was evaluated through a bead clearance assay. Explants were infected with a swine H1N1 influenza virus. Influenza infection of epithelial cells was confirmed by immunohistochemistry and viral replication was quantified by plaque assays and real-time RT-PCR. Results Histological analysis and bead clearance assay showed that the tissue architecture of the explants was maintained for up to 7 days, while ciliary movement exhibited a gradual decrease after 4 days. Challenge with swine H1N1 influenza virus showed that the EVOC tracheal system shows histological changes consistent with in vivo influenza infection and supported productive viral replication over multiple cycles of infection. Conclusion The air interface EVOC system using pig trachea described here constitutes a useful biological tool with a wide range of applications in the study of influenza infection. [source] Influenza virus assays based on virus-inducible reporter cell linesINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5 2009Yunsheng Li Background, Virus-inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus-induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus-inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5,- and 3,-untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus-inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Findings, Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose-dependent and highly specific for influenza A or influenza B viruses. Conclusions, These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers. [source] Heterosubtypic T-cell responses against avian influenza H5 haemagglutinin are frequently detected in individuals vaccinated against or previously infected with human subtypes of influenzaINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 4 2008Kylie Goy Background, Cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti-viral cytokines and killing infected cells in the lung. Heterosubtypic T-cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with H5N1 infection in animal challenge models. Therefore, existing T-cell responses induced by natural infection or vaccination in humans may provide some degree of protection from infection with H5N1 strains, or may attenuate the severity of disease. Objectives, To investigate heterosubtypic T-cell responses to avian influenza in humans. Methods, T-cell responses to an overlapping set of H5 HA peptides and inactivated viruses (H1N1, H3N2 and H5N1) were assessed using IFN-, and IL-2 enzyme-linked immunospot (ELISpot) assays in a cohort of adults either vaccinated against seasonal influenza in the last 3 years (n = 20) or previously infected (n = 40). Results, T-cell responses to all three subtypes of virus were found in both infected and vaccinated individuals by IFN-, and IL-2 ELISpot assays. Approximately half of the participants from each group had a positive T-cell response to the H5 HA peptides in the IFN-, or IL-2 ELISpot assay. Conclusions, Heterosubtypic T-cell responses to H5 HA occur quite frequently in vaccinated and infected individuals. Further investigation of these responses and what role they may play upon challenge or vaccination against H5N1 may assist in vaccine design for avian influenza. [source] Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCsINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 2 2008Felix Geeraedts Background, For protection against (re-)infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives, The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods, Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions, In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination-inhibition titers and virus-neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN-,-producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN-, by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines. [source] Chest CT findings of influenza virus-associated pneumonia in 12 adult patientsINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5-6 2007Jiro Fujita Objective, In this study, we describe the chest computed tomography findings of influenza virus-associated pneumonia in adult patients. Methods, Our retrospective study included 12 adult patients who had proven influenza virus - associated pneumonia. Results, Out of 12 patients, six were diagnosed as having pure influenza virus pneumonia, five as having bronchopneumonia caused by bacteria associated with influenza A infection, and one as having a cryptogenic organizing pneumonia associated with influenza A infection. Conclusion, Radiographic findings of influenza virus pneumonia in adult patients consist of ground-glass attenuation. Localized patchy consolidations were observed in cases of bronchopneumonia. [source] Surveillance for highly pathogenic avian influenza in wild birds in the USAINTEGRATIVE ZOOLOGY (ELECTRONIC), Issue 4 2009Thomas J. DELIBERTO Abstract As part of the USA's National Strategy for Pandemic Influenza, an Interagency Strategic Plan for the Early Detection of Highly Pathogenic H5N1 Avian Influenza in Wild Migratory Birds was developed and implemented. From 1 April 2006 through 31 March 2009, 261 946 samples from wild birds and 101 457 wild bird fecal samples were collected in the USA; no highly pathogenic avian influenza was detected. The United States Department of Agriculture, and state and tribal cooperators accounted for 213 115 (81%) of the wild bird samples collected; 31, 27, 21 and 21% of the samples were collected from the Atlantic, Pacific, Central and Mississippi flyways, respectively. More than 250 species of wild birds in all 50 states were sampled. The majority of wild birds (86%) were dabbling ducks, geese, swans and shorebirds. The apparent prevalence of low pathogenic avian influenza viruses during biological years 2007 and 2008 was 9.7 and 11.0%, respectively. The apparent prevalence of H5 and H7 subtypes across all species sampled were 0.5 and 0.06%, respectively. The pooled fecal samples (n= 101 539) positive for low pathogenic avian influenza were 4.0, 6.7 and 4.7% for biological years 2006, 2007 and 2008, respectively. The highly pathogenic early detection system for wild birds developed and implemented in the USA represents the largest coordinated wildlife disease surveillance system ever conducted. This effort provided evidence that wild birds in the USA were free of highly pathogenic avian influenza virus (given the expected minimum prevalence of 0.001%) at the 99.9% confidence level during the surveillance period. [source] Development of a consensus microarray method for identification of some highly pathogenic virusesJOURNAL OF MEDICAL VIROLOGY, Issue 11 2009Kang Xiao-Ping Abstract Some highly pathogenic viruses, such as Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Hanta virus, SARS-CoV, and H5N1 avian influenza virus can cause severe infectious diseases. However, the consensus method for detecting these viruses has not been well established. A rapid and sensitive microarray approach for detection of these viruses and a panel of specific probes covering nine genera and 16 virus species were designed. 70-mer oligonucleotides were used at the genus level and 50-mer oligonucleotides were at the species level, respectively. To decrease the interference of the host genome in hybridization, the consensus genus primers were designed and used to reverse transcribe only virus genome. The synthesis of the second strand was carried out with a random primer sequence (5,-GTTTCCCAGTAGGTCTCNNNNNNNN-3,). The amplified products were labeled and processed for microarray analyses. This microarray-based method used the highly conserved consensus primers to synthesize specifically the virus cDNA and could identify effectively Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Tick borne encephalitis virus, and H5N1 avian influenza virus. Using this method, one unknown virus isolated from pig brain in Shanxi Province, China was identified. This method may have an important potential application for the diagnosis of virus infection. J. Med. Virol. 81:1945,1950, 2009. © 2009 Wiley-Liss, Inc. [source] Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipientsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2006Giuseppe Gerna Abstract Viral respiratory tract infections in lung transplant recipients may be severe. During three consecutive winter-spring seasons, 49 symptomatic lung transplant recipients with suspected respiratory viral infection, and 26 asymptomatic patients were investigated for presence of respiratory viruses either in 56 nasopharyngeal aspirate or 72 bronchoalveolar lavage samples taken at different times after transplantation. On the whole, 1 asymptomatic (3.4%) and 28 symptomatic (57.1%) patients were positive for human metapneumovirus (hMPV, 4 patients), influenza virus A (3 patients), and B (2 patients), respiratory syncytial virus (2 patients), human coronavirus (2 patients), human parainfluenza virus (2 patients), rhinovirus (5 patients), while 4 patients were coinfected by 2 respiratory viruses, and 5 were infected sequentially by 2 or more respiratory viruses. In bronchoalveolar lavage samples, hMPV predominated by far over the other viruses, being responsible for 60% of positive specimens, whereas other viruses were present in nasopharyngeal aspirates at a comparable rate. RT-PCR (detecting 43 positive samples/128 examined) was largely superior to monoclonal antibodies (detecting 17 positive samples only). In addition, HCMV was detected in association with a respiratory virus in 4/18 HCMV-positive patients, and was found at a high concentration (>105 DNA copies/ml) in 3/16 (18.7%) patients with HCMV-positive bronchoalveolar lavage samples and pneumonia. Coinfections and sequential infections by HCMV and respiratory viruses were significantly more frequent in patients with acute rejection and steroid treatment. In conclusion: (i) about 50% of respiratory tract infections of lung transplant recipients were associated with one or more respiratory viruses; (ii) hMPV largely predominates in bronchoalveolar lavage of symptomatic lung transplant recipients, thus suggesting a causative role in lower respiratory tract infections; (iii) RT-PCR appears to be the method of choice for detection of respiratory viruses in lung transplant recipients, (iv) a high HCMV load in bronchoalveolar lavage is a risk factor for viral pneumonia, suggesting some measure of intervention for the control of viral infection. J. Med. Virol. 78:408,416, 2006. © 2006 Wiley-Liss, Inc. [source] A comparison of epidemiologic and immunologic features of bronchiolitis caused by influenza virus and respiratory syncytial virusJOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Roberto P. Garofalo Abstract We studied epidemiologic and immunologic factors in infants with bronchiolitis caused by influenza virus. The proportion of these infants who were male and who had an immediate family member with a history of asthma was similar to that of a control group of infants with respiratory syncytial virus (RSV) bronchiolitis. In subjects with influenza virus infection, concentrations of the beta chemokine macrophage inflammatory protein-1alpha (MIP-1,), but not other beta chemokines, in nasopharyngeal secretions (NPS) were greater among infants with more severe, hypoxic bronchiolitis than in subjects with mild, nonhypoxic bronchiolitis, or upper respiratory tract infection alone. Quantities of MIP-1, were also correlated with lower values of oxygen saturation. These findings point out epidemiologic and immunologic similarities between bronchiolitis caused by influenza and RSV, and suggest that host factors are more important than the nature of the infecting virus in the development of severe forms of bronchiolitis caused by influenza and RSV. J. Med. Virol. 75:282,289, 2005. © 2004 Wiley-Liss, Inc. [source] Pharmaceutical and immunological evaluation of human papillomavirus viruslike particle as an antigen carrierJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Roxana M. Ionescu Abstract We report the preparation and the immunogenicity of a conjugate vaccine obtained by chemically conjugating a variant of the extracellular peptide fragment of influenza type A M2 protein to the human papillomavirus (HPV) viruslike particle (VLP). Conjugates comprised of approximately 4000 copies of the antigenic peptide per VLP are obtained as the result of the reaction between a C-terminal cysteine residue on the peptide and the maleimide-activated HPV VLP. The resulting conjugates have an average particle size slightly larger than the carrier and present enhanced overall stability against chemical and thermal-induced denaturation. The M2-HPV VLP conjugates lost the binding affinity for anti-HPV conformational antibodies but retained reactivity to a M2-specific monoclonal antibody. The conjugate vaccine formulated with aluminum adjuvant and delivered in two doses of 30-ng peptide was found to be highly immunogenic and conferred good protection against lethal challenge of influenza virus in mice. These results suggest that HPV VLP can be used as a carrier for synthetic or small antigens for the development of subunit vaccines. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:70,79, 2006 [source] Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming MiceALCOHOLISM, Issue 8 2010Ryan A. Langlois Background:, Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods:, BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results:, Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions:, Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol. [source] Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infectionLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2010M. Kawase Abstract Aims:, Our study was conducted to evaluate the potent protective effects of oral administration of probiotic Lactobacillus strains against influenza virus (Flu) infection in a mouse model. Method and Results:, Lyophilized Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri TMC0356 (TMC0356) were orally administered to BALB/c mice for 19 days. The test mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and any changes in clinical symptoms were monitored. After 6 days of infection, the mice were killed and pulmonary virus titres were determined. The clinical symptom scores of mice administered oral LGG and TMC0356 were significantly ameliorated, compared to those of the control mice (P < 0·01). The pulmonary virus titres of the mice fed LGG and TMC0356 were also significantly decreased compared to those of control mice (P < 0·05). Conclusions:, These results indicate that oral administration of lactobacilli, such as LGG and TMC0356, might protect a host animal against Flu infection. Significance and Impact of the Study:, These results demonstrate that oral administration of selected lactobacilli might protect host animals from Flu infection by interactions with gut immunity. [source] Mass spectrometry analysis of the influenza virus,MASS SPECTROMETRY REVIEWS, Issue 1 2009Kevin M. Downard Abstract The role of mass spectrometry to probe characteristics of the influenza virus, and vaccine and antiviral drugs that target the virus, are reviewed. Genetic and proteomic approaches have been applied which incorporate high resolution mass spectrometry and mass mapping to genotype the virus and establish its evolution in terms of the primary structure of the surface protein antigens. A mass spectrometric immunoassay has been developed and applied to assess the structure and antigenicity of the virus in terms of the hemagglutinin antigen. The quantitation of the hemagglutinin antigen in vaccine preparations has also been conducted that is of importance to their efficacy. Finally, the characterization and quantitation of antiviral drugs against the virus, and their metabolites, have been monitored in blood, serum, and urine. The combined approaches demonstrate the strengths of modern mass spectrometric methods for the characterization of this killer virus. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:35,49, 2009 [This article was published online 10 September 2008. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 7 November 2008.] [source] | ||||||||||||||||||||||||||||