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Influenza H1n1

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https://www.readbyqxmd.com/read/28646652/influenza-a-virus-cap-snatches-host-rnas-based-on-their-abundance-early-after-infection
#1
Dorota Sikora, Lynda Rocheleau, Earl G Brown, Martin Pelchat
The influenza A virus RNA polymerase cleaves the 5' ends of host RNAs and uses these RNA fragments as primers for viral mRNA synthesis. We performed deep sequencing of the 5' host-derived ends of the eight viral mRNAs of influenza A/Puerto Rico/8/1934 (H1N1) virus in infected A549 cells, and compared the population to those of A/Hong Kong/1/1968 (H3N2) and A/WSN/1933 (H1N1). In the three strains, the viral RNAs target different populations of host RNAs. Host RNAs are cap-snatched based on their abundance, and we found that RNAs encoding proteins involved in metabolism are overrepresented in the cap-snatched populations...
June 21, 2017: Virology
https://www.readbyqxmd.com/read/28646559/pandemic-h1n1-2009-influenza-a-virus-infection-associated-with-respiratory-signs-in-sloth-bears-melursus-ursinus
#2
N C Boedeker, M I Nelson, M L Killian, M K Torchetti, T Barthel, S Murray
In 2009, a pandemic influenza A virus (pH1N1) spread globally in humans and infected a broad range of captive animals with close human contact. In February 2014, a pH1N1 virus was isolated from a sloth bear with respiratory signs at a US zoo, demonstrating that recurring epidemics present an ongoing threat to animals, including threatened species. This is the first report of pH1N1 infection in sloth bears. To understand the sloth bear virus within the global context of pH1N1, phylogenetic trees were inferred including full-length sequences from available non-human, non-swine hosts, representing four families in the order Carnivora and one order of birds...
June 23, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#3
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642154/a-boosting-skin-vaccination-with-dissolving-microneedle-patch-encapsulating-m2e-vaccine-broadens-the-protective-efficacy-of-conventional-influenza-vaccines
#4
Wandi Zhu, Winston Pewin, Chao Wang, Yuan Luo, Gilbert X Gonzalez, Teena Mohan, Mark R Prausnitz, Bao-Zhong Wang
The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulated into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone...
June 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28640212/synthesis-and-in-vitro-anti-influenza-virus-evaluation-of-novel-sialic-acid-c-5-and-c-9-pentacyclic-triterpene-derivatives
#5
Xu Han, Long-Long Si, Yong-Ying Shi, Zi-Bo Fan, Shou-Xin Wang, Zhen-Yu Tian, Man Li, Jia-Qi Sun, Ping-Xuan Jiao, Fu-Xiang Ran, Yong-Min Zhang, De-Min Zhou, Su-Long Xiao
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28637755/seasonal-h3n2-and-2009-pandemic-h1n1-influenza-a-viruses-reassort-efficiently-but-produce-attenuated-progeny
#6
Kara L Phipps, Nicolle Marshall, Hui Tao, Shamika Danzy, Nina Onuoha, John Steel, Anice C Lowen
Reassortment of gene segments between co-infecting influenza A viruses (IAV) facilitates viral diversification and has significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have co-circulated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous co-infections with pH1N1 and H3N2 viruses were compared to those obtained following co-infection with homologous, genetically tagged, pH1N1 viruses as a control...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637754/functional-evolution-of-influenza-ns1-protein-in-currently-circulating-human-2009-pandemic-h1n1-viruses
#7
Amelia M Clark, Aitor Nogales, Luis Martinez-Sobrido, David J Topham, Marta L DeDiego
In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist, but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here, we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637750/interplay-of-pa-x-and-ns1-proteins-in-replication-and-pathogenesis-of-a-temperature-sensitive-2009-pandemic-h1n1-influenza-a-virus
#8
Aitor Nogales, Laura Rodriguez, Marta L DeDiego, David J Topham, Luis Martínez-Sobrido
Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics, representing a serious public health concern. It has been described that one mechanism used by some IAV strains to escape the host innate immune responses and modulate virus pathogenicity involves the ability of PA-X and NS1 proteins to inhibit the host protein synthesis in infected cells. It was reported that for the 2009 pandemic H1N1 IAV (pH1N1) only the PA-X protein has this inhibiting capability while the NS1 protein did not...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28636443/personal-protective-equipment-supply-chain-lessons-learned-from-recent-public-health-emergency-responses
#9
Anita Patel, Maryann M D'Alessandro, Karen J Ireland, W Greg Burel, Elaine B Wencil, Sonja A Rasmussen
Personal protective equipment (PPE) that protects healthcare workers from infection is a critical component of infection control strategies in healthcare settings. During a public health emergency response, protecting healthcare workers from infectious disease is essential, given that they provide clinical care to those who fall ill, have a high risk of exposure, and need to be assured of occupational safety. Like most goods in the United States, the PPE market supply is based on demand. The US PPE supply chain has minimal ability to rapidly surge production, resulting in challenges to meeting large unexpected increases in demand that might occur during a public health emergency...
May 2017: Health Security
https://www.readbyqxmd.com/read/28635259/a-delivery-system-targeting-haemagglutinin-of-influenza-virus-a-to-facilitate-antisense-based-anti-h1n1-therapy
#10
Xiaoran Ding, Jing Yang, Dandan Lu, Qingjun Li, Zhaoyan Zhang, Zhe Zhou, Shengqi Wang
Antisense oligonucleotides (ODNs) are therapeutic molecules that hybridize to complementary target mRNA sequences. To further overcome the poor cellular uptake of ODNs, we proposed a novel strategy to deliver ODNs by conjugating the anti-influenza A virus (IAV) ODN with a peptide showing high affinity to the haemagglutinin (HA) on the surface of IAV particles or the IAV infected host cells. The HA-specific binding peptides were selected by phage display and the individual binding clones are characterized by DNA sequencing, and the selected phage was further assayed by ELISA...
June 21, 2017: Bioconjugate Chemistry
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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 15, 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
#17
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
#18
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
#19
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
#20
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
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