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Antoine Nougairède Laetitia Ninove Christine Zandotti Nicolas Salez Karine Mantey Noémie Resseguier Céline Gazin Didier Raoult Rémi N. Charrel Xavier de Lamballerie 《PloS one》2010,5(2)
Background
In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones.Methodology/Principal Findings
We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed.Conclusions/Significance
This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases. 相似文献3.
Takayuki Morishita Shinichi Kobayashi Takashi Miyake Yuichi Ishihara Setsuko Nakajima Katsuhisa Nakajima 《Microbiology and immunology》1993,37(8):661-665
H1N1 strains of influenza A virus isolated during the influenza season of 1991–92 were divided into two groups according to the property of host-specific hemagglutination. Group 1 viruses agglutinated human and chicken red blood cells. Group 2 viruses agglutinated human but not chicken red blood cells. The viruses of both groups, however, showed the same antigenic structure determined with ferret antisera. The virus clones which were plaque-purified twice from a group 2 virus retained the characteristic of host-specific hemagglutination after five successive passages in MDCK cells, indicating that this phenomenon is genetically determined. However, the amino acid, sequences of the hemagglutinin (HA) polypeptides deduced from the nucleotide sequences of the HA gene of the two groups did not show any differences between them. This suggests a difference in amino acids in some other polypeptide(s), which affects the host-specific hemagglutination. 相似文献
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Mahesh Khatri Varun Dwivedi Steven Krakowka Cordelia Manickam Ahmed Ali Leyi Wang Zhuoming Qin Gourapura J. Renukaradhya Chang-Won Lee 《Journal of virology》2010,84(21):11210-11218
Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.Swine influenza is a highly contagious, acute respiratory viral disease of swine. The causative agent, swine influenza virus (SwIV), is a strain of influenza virus A in the Orthomyxoviridae family. Clinical disease in pigs is characterized by sudden onset of anorexia, weight loss, dyspnea, pyrexia, cough, fever, and nasal discharge (21). Porcine respiratory tract epithelial cells express sialic acid receptors utilized by both avian (α-2,3 SA-galactose) and mammalian (α-2,6 SA-galactose) influenza viruses. Thus, pigs can serve as “mixing vessels” for the generation of new reassortant strains of influenza A virus that may contain RNA elements of both mammalian and avian viruses. These “newly generated” and reassorted viruses may have the potential to cause pandemics in humans and enzootics in animals (52).Occasional transmission of SwIV to humans has been reported (34, 43, 52), and a few of these cases resulted in human deaths. In April 2009, a previously undescribed H1N1 influenza virus was isolated from humans in Mexico. This virus has spread efficiently among humans and resulted in the current human influenza pandemic. Pandemic H1N1 virus is a triple reassortant (TR) virus of swine origin that contains gene segments from swine, human, and avian influenza viruses. Considering the pandemic potential of swine H1N1 viruses, it is important to understand the pathogenesis and mucosal immune responses of these viruses in their natural host. Swine can serve as an excellent animal model for the influenza virus pathogenesis studies. The clinical manifestations and pathogenesis of influenza in pigs closely resemble those observed in humans. Like humans, pigs are also outbred species, and they are physiologically, anatomically, and immunologically similar to humans (9, 23, 39, 40). In contrast to the mouse lung, the porcine lung has marked similarities to its human counterpart in terms of its tracheobronchial tree structure, lung physiology, airway morphology, abundance of airway submucosal glands, and patterns of glycoprotein synthesis (8, 10, 17). Furthermore, the cytokine responses in bronchoalveolar lavage (BAL) fluid from SwIV-infected pigs are also identical to those observed for nasal lavage fluids of experimentally infected humans (20). These observations support the idea that the pig can serve as an excellent animal model to study the pathogenesis of influenza virus.Swine influenza virus causes an acute respiratory tract infection. Virus replicates extensively in epithelial cells of the bronchi and alveoli for 5 to 6 days followed by clearance of viremia by 1 week postinfection (48). During the acute phase of the disease, cytokines such as alpha interferon (IFN-α), tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-12, and gamma interferon (IFN-γ) are produced. These immune responses mediate both the clinical signs and pulmonary lesions (2). In acute SwIV-infected pigs, a positive correlation between cytokines in BAL fluid, lung viral titers, inflammatory cell infiltrates, and clinical signs has been detected (2, 48).Infection of pigs with SwIV of one subtype may confer complete protection from subsequent infections by homologous viruses and also partial protection against heterologous subtypes, but the nature of the immune responses generated in the swine are not fully delineated. Importantly, knowledge related to host mucosal immune responses in the SwIV-infected pigs is limited. So far only the protective virus-specific IgA and IgG responses in nasal washes and BAL fluid, as well as IgA, IgG, and IgM responses in the sera of infected pigs, have been reported (28). Pigs infected with H3N2 and H1N1 viruses have an increased frequency of neutrophils, NK cells, and CD4 and CD8 T cells in the BAL fluid (21). Pigs infected with the pandemic H1N1 virus showed activated CD4 and CD8 T cells in the peripheral blood on postinfection day (PID) 6 (27). Proliferating lymphocytes in BAL fluid and blood and virus-specific IFN-γ-secreting cells in the tracheobronchial lymph nodes (TBLN) and spleen were detected in SwIV-infected pigs (7). Limited information is available on the mucosal immune responses in pig lungs infected with SwIV, which has a history of transmission to humans.In this study, we examined the acute infection of SwIV (strain SwIV OH07) in pigs with respect to viral replication, pathology, and innate and adaptive immune responses in the respiratory tract of these pigs. This virus was isolated from pigs which suffered from respiratory disease in Ohio, and the same virus was also transmitted to humans and caused clinical disease (43, 55). Interestingly, like pandemic H1N1 influenza virus, SwIV also infects the lower respiratory tract of pigs. Delineation of detailed mucosal immune responses generated in pig lungs during acute SwIV OH07 infection may provide new insights for the development of therapeutic strategies for better control of virus-induced inflammation and for the design and testing of effective vaccines. 相似文献
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In March 2013 a new avian influenza A(H7N9) virus emerged in China and infected humans with a case fatality rate of over 30%. Like the highly pathogenic H5N1 virus, H7N9 virus is causing severe respiratory distress syndrome in most patients. Based on genetic analysis this avian influenza A virus shows to some extent adaptation to mammalian host. In the present study, we analyzed the activation of innate immune responses by this novel H7N9 influenza A virus and compared these responses to those induced by the avian H5N1 and seasonal H3N2 viruses in human monocyte-derived dendritic cells (moDCs). We observed that in H7N9 virus-infected cells, interferon (IFN) responses were weak although the virus replicated as well as the H5N1 and H3N2 viruses in moDCs. H7N9 virus-induced expression of pro-inflammatory cytokines remained at a significantly lower level as compared to H5N1 virus-induced “cytokine storm” seen in human moDCs. However, the H7N9 virus was extremely sensitive to the antiviral effects of IFN-α and IFN-β in pretreated cells. Our data indicates that different highly pathogenic avian viruses may show considerable differences in their ability to induce host antiviral responses in human primary cell models such as moDCs. The unexpected appearance of the novel H7N9 virus clearly emphasizes the importance of the global influenza surveillance system. It is, however, equally important to systematically characterize in normal human cells the replication capacity of the new viruses and their ability to induce and respond to natural antiviral substances such as IFNs. 相似文献
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Background
In late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission.Methodology/Principals
We developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available.Conclusions/Significance
Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation. 相似文献7.
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目的建立一种快速定量检测季节性流感病毒H1N1核酸的实时荧光定量PCR检测方法及试剂盒。方法选择季节性流感病毒H1N1的保守基因NP基因作为检测靶目标,应用Clustal W软件进行序列同源性比对分析,筛选出季节性流感病毒H1N1特异性的保守序列作为引物候选区域,然后应用Primer Express及PrimerPremier 5.0软件包对候选引物进行进一步配对及筛选,得到最优特异性检测引物。同时,由病毒全长cDNA扩增出NP基因,琼脂糖凝胶电泳检测NP基因的扩增情况并对目的条带进行切胶回收及纯化,对回收后的NP全长基因进行核酸浓度测定,并换算成拷贝数,作为定量标准品。结果应用ABI公司的Power SYBR Green PCR MasterMix及StepOne实时荧光定量PCR仪,该检测系统灵敏度可达102 copies/μL,不同梯度标准品间线性关系(R2)达0.999,斜率为-0.3433,扩增效率为95.572%,所有标准品均在83.2℃出现尖且窄的特异性熔解峰。结论利用该检测系统可以快速定量检测季节性流感病毒H1N1,灵敏度高,可用作基础及临床实验室对季节性流感病毒H1N1感染的辅助诊断方法和临床效果的监测手段,对实验操作者要求相对较低,具有实际的应用价值。 相似文献
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Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV) as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA) or nucleoprotein (NP) of the highly pathogenic avian influenza virus (HPAIV) H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m.) injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8) influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV. 相似文献
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Background
The current spread of pandemic influenza A(H1N1)v virus necessitates an intensified surveillance of influenza virus infections worldwide. So far, in many laboratories routine diagnostics were limited to generic influenza virus detection only. To provide interested laboratories with real-time PCR assays for type and subtype identification, we present a bundle of PCR assays with which any human influenza A and B virus can be easily identified, including assays for the detection of the pandemic A(H1N1)v virus.Principal Findings
The assays show optimal performance characteristics in their validation on plasmids containing the respective assay target sequences. All assays have furthermore been applied to several thousand clinical samples since 2007 (assays for seasonal influenza) and April 2009 (pandemic influenza assays), respectively, and showed excellent results also on clinical material.Conclusions
We consider the presented assays to be well suited for the detection and subtyping of circulating influenza viruses. 相似文献15.
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Aymn E. Rashad Ahmed H. Shamroukh Randa E. Abdel-Megeid Ahmed Mostafa Mohamed A. Ali Klaus Banert 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):809-820
Treatment of 5-amino-1-(9-methyl-5,6-dihydronaphtho[1′,2′:4,5]thieno[2,3-d]pyrimidin-11-yl)-1H-pyrazole-4-carbonitrile (1) with formic acid afforded pyrazolo[3,4-d]pyrimidin-4-one derivative 2. The sodium salt of the latter compound (generated in situ) was treated with some alkyl halides to afford the corresponding N-substituted compounds 3–7. The siloxy derivative 8 (generated also in situ from 2) was ribosylated and glycosylated to yield compounds 9 and 11, respectively. Deprotection of compounds 9 and 11 in methanolic ammonia produced the free nucleosides 10 and 12, respectively. Moreover, the prepared compounds were tested for antiviral activity against H5N1 virus [A/chicken/Egypt/1/2006] and some of them revealed moderate results compared with the other tested compounds. 相似文献
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Ren Lehao Zhang Wanju Zhang Jing Zhang Jiaxiang Zhang Huiying Zhu Yong Meng Xiaoxiao Yi Zhigang Wang Ruilan 《中国病毒学》2021,36(6):1532-1542
Virologica Sinica - Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A... 相似文献
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