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https://www.readbyqxmd.com/read/28631598/in-vitro-and-in-vivo-evidence-of-a-potential-a-h1n1-pdm09-antigenic-drift-mediated-by-escape-mutations-in-the-haemagglutinin-sa-antigenic-site
#1
Miguel Retamal, Yacine Abed, Chantal Rhéaume, Mariana Baz, Guy Boivin
Influenza A(H1N1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. By using escape mutants, we previously identified six haemagglutinin (HA) changes (T80R, G143E, G158E, N159D, K166E and A198E) that were located within antigenic sites. Combinations of these mutations were introduced into the A(H1N1)pdm09 HA plasmid by mutagenesis. Reassortant 6 : 2 viruses containing both the HA and NA genes of the A(H1N1)pdm09 and the six internal gene segments of A/PR/8/34 were rescued by reverse genetics...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630402/exploration-of-binding-and-inhibition-mechanism-of-a-small-molecule-inhibitor-of-influenza-virus-h1n1-hemagglutinin-by-molecular-dynamics-simulation
#2
Shanshan Guan, Tianao Wang, Ziyu Kuai, Mengdan Qian, Xiaopian Tian, Xiuqi Zhang, Yongjiao Yu, Song Wang, Hao Zhang, Hao Li, Wei Kong, Yaming Shan
Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629724/in-vitro-antiviral-effects-of-peganum-harmala-seed-extract-and-its-total-alkaloids-against-influenza-virus
#3
Mohammad-Taghi Moradi, Ali Karimi, Mahmoud Rafieian-Kopaei, Fatemeh Fotouhi
This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28625047/asymmetric-synthesis-of-the-antiviral-diterpene-wickerol-a
#4
Shu-An Liu, Dirk Trauner
Wickerol A (1) is an unusual diterpene with remarkable activity against H1N1 influenza virus. Its tetracyclic skeleton contains three quaternary carbons and is marked by several syn-pentane interactions which force a six-membered ring into a twist-boat conformation. We present an asymmetric synthesis of wickerol A (1) that is based on a Jung Diels-Alder reaction, an intramolecular alkylation to complete the 6-5-6-6 ring system, and a conjugate addition, all of which overcome considerable steric strain. During the synthesis, we isolated an unusual cyclopropane, which presumably stems from a carbonium ion...
June 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28624926/limited-awareness-of-animal-influenza-prevention-and-control-among-dai-lue-smallholder-farmers-in-southwest-china
#5
Xiang Zhao, Gareth Davey
Awareness of animal influenza and its prevention and control is important for ensuring livestock health, production and welfare. In China, a country stereotyped as a major source of emerging zoonotic infectious diseases, research on the public understanding of animal influenza is limited to the Han, the main ethnic group. The present qualitative study in Southwest China investigated awareness of animal influenza among the Dai, an ethnic minority. The participants (15 men and 10 women, ages 18-83) were smallholder farmers of pigs and poultry in rural areas of Jinghong, Xishuangbanna, Yunnan Province...
June 17, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28624584/antibody-dependent-nk-cell-degranulation-as-a-marker-for-assessing-antibody-dependent-cytotoxicity-against-pandemic-2009-influenza-a-h1n1-infection-in-human-plasma-and-influenza-vaccinated-transchromosomic-bovine-intravenous-immunoglobulin-therapy
#6
Brian J Morrison, Jessica A Roman, Thomas C Luke, Nishith Nagabhushana, Kanakatte Raviprakash, Maya Williams, Peifang Sun
This study describes an antibody-dependent NK cell degranulation assay, as a biomarker to assess antibody-dependent cellular cytotoxicity (ADCC) response in influenza plasma and for antibody therapies against influenza infection. The concentration of neutralizing antibodies (NAbs) against the hemagglutinin receptor of influenza viruses is a current determinant in protection against infection, particularly following receipt of the seasonal influenza vaccine. However, this is a limited assessment of protection, because: (i) NAb titers that incur full protection vary; and (ii) NAb titers do not account for the entire breadth of antibody responses against viral infection...
June 14, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28622865/pa-x-protein-decreases-replication-and-pathogenicity-of-swine-influenza-virus-in-cultured-cells-and-mouse-models
#7
Xiao-Qian Gong, Ying-Feng Sun, Bao-Yang Ruan, Xiao-Min Liu, Qi Wang, Hai-Ming Yang, Shuai-Yong Wang, Peng Zhang, Xiu-Hui Wang, Tong-Ling Shan, Wu Tong, Yan-Jun Zhou, Guo-Xin Li, Hao Zheng, Guang-Zhi Tong, Hai Yu
Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28622854/linear-dna-vaccine-prepared-by-large-scale-pcr-provides-protective-immunity-against-h1n1-influenza-virus-infection-in-mice
#8
Fei Wang, Quanjiao Chen, Shuntang Li, Chenyao Zhang, Shanshan Li, Min Liu, Kun Mei, Chunhua Li, Lixin Ma, Xiaolan Yu
Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28618270/diversity-of-functionally-permissive-sequences-in-the-receptor-binding-site-of-influenza-hemagglutinin
#9
Nicholas C Wu, Jia Xie, Tianqing Zheng, Corwin M Nycholat, Geramie Grande, James C Paulson, Richard A Lerner, Ian A Wilson
Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28615200/kallikrein-related-peptidase-5-contributes-to-h3n2-influenza-virus-infection-in-human-lungs
#10
Melia Magnen, Fabien Gueugnon, Antoine Guillon, Thomas Baranek, Virginie C Thibault, Agnès Petit-Courty, Simon J de Veer, Jonathan Harris, Alison A Humbles, Mustapha Si-Tahar, Yves Courty
The HA (hemagglutinin) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies have indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating the HA of seasonal influenza A viruses (IAV) in humans. This study focuses on human KLK1 and KLK5, two of the 15 serine proteases known as the kallikrein-related peptidases (KLK)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614376/effect-of-previous-and-current-vaccination-against-influenza-a-h1n1-pdm09-a-h3n2-and-b-during-the-post-pandemic-period-2010-2016-in-spain
#11
Alin Gherasim, Iván Martínez-Baz, Jesús Castilla, Francisco Pozo, Amparo Larrauri
BACKGROUND: Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. METHODS: We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus...
2017: PloS One
https://www.readbyqxmd.com/read/28611246/inhibition-of-avian-influenza-a-virus-replication-in-human-cells-by-host-restriction-factor-tufm-is-correlated-with-autophagy
#12
Shu-Ming Kuo, Chi-Jene Chen, Shih-Cheng Chang, Tzu-Jou Liu, Yi-Hsiang Chen, Sheng-Yu Huang, Shin-Ru Shih
Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2627E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2627K (human signature) and PB2627E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2627E than PB2627K in transfected human cells...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28609011/the-highly-pathogenic-h5n1-influenza-a-virus-down-regulated-several-cellular-micrornas-which-target-viral-genome
#13
Rong Wang, Ying-Ying Zhang, Jian-Sheng Lu, Bing-Hui Xia, Zhi-Xin Yang, Xu-Dong Zhu, Xiao-Wei Zhou, Pei-Tang Huang
Higher and prolonged viral replication is critical for the increased pathogenesis of the highly pathogenic avian influenza (HPAI) subtype of H5N1 influenza A virus (IAV) over the lowly pathogenic H1N1 IAV strain. Recent studies highlighted the considerable roles of cellular miRNAs in host defence against viral infection. In this report, using a 3'UTR reporter system, we identified several putative miRNA target sites buried in the H5N1 virus genome. We found two miRNAs, miR-584-5p and miR-1249, that matched with the PB2 binding sequence...
June 13, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28606815/predictors-of-self-and-parental-vaccination-decisions-in-england-during-the-2009-h1n1-pandemic-analysis-of-the-flu-watch-pandemic-cohort-data
#14
Dale Weston, Ruth Blackburn, Henry W W Potts, Andrew C Hayward
During the 2009 H1N1 pandemic, UK uptake of the pandemic influenza vaccine was very low. Furthermore, attitudes governing UK vaccination uptake during a pandemic are poorly characterised. To the best of our knowledge, there is no published research explicitly considering predictors of both adult self-vaccination and decisions regarding whether or not to vaccinate one's children among the UK population during the H1N1 pandemic. We therefore aimed to identify predictors of both self-vaccination decisions and parental vaccination decisions using data collected during the H1N1 pandemic as part of the Flu Watch cohort study...
June 7, 2017: Vaccine
https://www.readbyqxmd.com/read/28603462/immune-response-to-seasonal-influenza-vaccine-in-patients-with-relapsing-remitting-multiple-sclerosis-receiving-long-term-daclizumab-beta-a-prospective-open-label-single-arm-study
#15
Lahar Mehta, Kimberly Umans, Gulden Ozen, Randy R Robinson, Jacob Elkins
BACKGROUND: For patients with relapsing-remitting multiple sclerosis (RRMS) undergoing continuous immunomodulatory therapy, understanding whether vaccinations can be performed safely and effectively is important. We tested the immune response to inactivated seasonal influenza vaccine during long-term daclizumab beta treatment. METHODS: In this prospective, open-label, single-arm extension SELECTED study, an optional vaccine substudy was performed on patients with RRMS who had already received daclizumab beta for 1 to 2 years in previous studies...
May 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/28601216/usefulness-of-ct-value-in-acute-respiratory-infections-caused-by-respiratory-syncytial-virus-a-and-b-and-influenza-virus-a-h1n1-pdm09-a-h3n2-and-b
#16
Jordi Reina, Carmen Morales, María Busquets, Cristina Norte
INTRODUCTION: Acute respiratory infections of viral cause are very frequent entities. The difficulty in evaluating the detection of a virus in these entities could be solved by determining the viral load. METHODS: A prospective study on the mean Ct value (cycle threshold value) detected against RSV-A, RSV-B and influenza A (H1N1)pdm09, A (H3N2) and B viruses in patients of different origin and age was performed. Detection was performed using a commercial molecular amplification (RT-PCR) technique...
June 7, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28598328/a-novel-twelve-class-fluctuation-test-reveals-higher-than-expected-mutation-rates-for-influenza-a-viruses
#17
Matthew D Pauly, Megan C Procario, Adam S Lauring
Influenza virus' low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the influenza virus mutation rate is 2.7x10(-6) - 3.0x10(-5) substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal fitness impacts and fluctuation tests typically investigate only a subset of all possible single nucleotide mutations. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins, which allowed us to measure the rates of selectively neutral mutations representative of the twelve different mutation types...
June 9, 2017: ELife
https://www.readbyqxmd.com/read/28598060/spontaneous-pneumothorax-in-h1n1-infection
#18
Ashutosh Chaturvedi, Arun Kumar
Spontaneous pneumothorax is a very rare entity in H1N1 infection unless it is co-existent with other respiratory conditions especially COPD. The other factors are old age, children below 5 years and patients with ILD. The mortality rate goes high with pulmonary illness complicated by H1N1 infection in smokers and in pregnant women. This is the first reported case of H1N1 infection with Spontaneous Pneumothorax in India.
May 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28594235/live-attenuated-auxotrophic-mutant-of-salmonella-typhimurium-expressing-immunogenic-ha1-protein-enhances-immunity-and-protective-efficacy-against-h1n1-influenza-virus-infection
#19
Nitin Machindra Kamble, Kim Je Hyoung, John Hwa Lee
AIM: To evaluate the efficacy of attenuated Salmonella typhimurium (JOL912) as a live bacterial vaccine vector. MATERIALS & METHODS: The JOL912 engineered to deliver HA1 protein from influenza A/Puerto Rico/8/1934 (H1N1; PR8) virus was coined as JOL1635 and further evaluated for immunogenicity and protective efficacy. RESULTS: The JOL1635 stably harbored the HA1 gene within pMMP65 plasmid with periplasmic expression and effective delivery of HA1 protein to RAW264...
June 8, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28588558/influenza-virus-and-glycemic-variability-in-diabetes-a-killer-combination
#20
Katina D Hulme, Linda A Gallo, Kirsty R Short
Following the 2009 H1N1 influenza virus pandemic, numerous studies identified the striking link between diabetes mellitus and influenza disease severity. Typically, influenza virus is a self-limiting infection but in individuals who have a pre-existing chronic illness, such as diabetes mellitus, severe influenza can develop. Here, we discuss the latest clinical and experimental evidence for the role of diabetes in predisposing the host to severe influenza. We explore the possible mechanisms that underlie this synergy and highlight the, as yet, unexplored role that blood glucose oscillations may play in disease development...
2017: Frontiers in Microbiology
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