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Meiyue Wang, Zhenyu Zhang, Xiaojun Wang
Tetherin/BST-2/CD317 is an interferon-induced host restriction factor that can block the budding of enveloped viruses by tethering them to the cell surface. Many viruses use certain proteins to counteract restriction by tetherin from their natural hosts, but not from other species. The influenza A virus (FLUAV) has a wide range of subtypes with different host tropisms. Human tetherin (huTHN) has been reported to restrict only specific FLUAV strains and the viral hemagglutinin (HA) and neuraminidase (NA) genes determine the sensitivity to huTHN...
May 16, 2018: Viruses
Ping He, Guojun Wang, Yanning Mo, Qingxiong Yu, Xiong Xiao, Wenjuan Yang, Weifeng Zhao, Xuan Guo, Qiong Chen, Jianqiao He, Mingli Liang, Jian Zhu, Yangbao Ding, Zuzhang Wei, Kang Ouyang, Fang Liu, Hui Jian, Weijian Huang, Adolfo García-Sastre, Ying Chen
Considered a "mixing vessel" for influenza viruses, pigs can give rise to new influenza virus reassortants that can threaten humans. During our surveillance of pigs in Guangxi, China from 2013 to 2015, we isolated 11 H1N1 and three H3N2 influenza A viruses of swine origin (IAVs-S). Out of the 14, we detected ten novel triple-reassortant viruses, which contained surface genes (hemagglutinin and neuraminidase) from Eurasian avian-like (EA) H1N1 or seasonal human-like H3N2, matrix (M) genes from H1N1/2009 pandemic or EA H1N1, nonstructural (NS) genes from classical swine, and the remaining genes from H1N1/2009 pandemic...
May 16, 2018: Emerging Microbes & Infections
Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi, Yusuke Ishikawa, Hiroki Yamaguchi, Kazuhito Shiosakai
To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2016-17 Japanese influenza season, we measured the 50% inhibitory concentration (IC50 ) of these NAIs for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2015-16 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate...
May 11, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Cheng Lu, Yan Yin, Fanli Meng, Yongbin Dun, Keke Pei, Chenlu Wang, Xu Xu, Fanhong Wu
Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4-phenylbut-3-en-2-ol (C1) had better inhibitory activities than 2-amino-1-arylethan-1-ol derivatives. To our surprise, sulfonation of C1 with 4-methoxybenzenesulfonyl chloride afforded more active inhibitor II with up to 6...
May 4, 2018: Bioorganic & Medicinal Chemistry Letters
Amaran Moodley, John S Bradley, David W Kimberlin
PURPOSE OF REVIEW: Influenza virus can cause severe or life-threatening infection in children. This review provides an update on antiviral medications available to treat and prevent influenza in both healthy children and children with underlying medical conditions, and recommendations on their appropriate use in the outpatient and inpatient settings. RECENT FINDINGS: Despite the significant morbidity and mortality associated with influenza infection, a large number of children hospitalized with influenza do not receive specific antiviral treatment with a neuraminidase inhibitor...
June 2018: Current Opinion in Pediatrics
Yulia Desheva, Ivan Sychev, Tatiana Smolonogina, Andrey Rekstin, Natalia Ilyushina, Vladimir Lugovtsev, Anastasia Samsonova, Aleksey Go, Anna Lerner
The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties...
2018: PloS One
Charlie S Bahnson, Rebecca L Poulson, Scott Krauss, Robert G Webster, David E Stallknecht
Influenza A virus (IAV) infections in shorebirds at Delaware Bay, New Jersey, USA, have historically included avian hemagglutinin (HA) subtypes H1-13, and H16. In a given year, infections are characterized by a limited number of HA and neuraminidase subtypes and a dominant HA subtype that often represents >50% of all isolates. Predominant HA subtypes shift between consecutive years. In addition, infection prevalence is consistently higher in Ruddy Turnstones ( Arenaria interpres morinella, RUTU) compared to Red Knots ( Calidris canutus rufa, REKN), despite comparable rates of exposure...
May 9, 2018: Journal of Wildlife Diseases
Tianbo Zhang, Mengjie Xiao, Chun-Kwok Wong, Ka-Pun Chris Mok, Xin Zhao, Huihui Ti, Pang-Chui Shaw
BACKGROUND: Sheng Jiang San (SJS), a multi-herb formulation, is used in treating high fever, thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza nowadays. However, there is no evidence-based investigation and mechanism research to support the anti-influenza efficacy of SJS. This study aims at evaluating the anti-influenza effect of SJS and investigating its possible mechanism. METHODS: The inhibitory effect of SJS against different influenza virus strains on MDCK cells was examined...
May 8, 2018: BMC Complementary and Alternative Medicine
Andrew C Y Lee, Kelvin K W To, Anna J X Zhang, Houshun Zhu, Can Li, Ricky R Zhang, Ivan F N Hung, Richard Y T Kao, Kwok-Hung Chan, Kwok-Yung Yuen
Seasonal influenza virus remains a common cause of mortality despite the use of neuraminidase inhibitors. This study evaluated the efficacy of a triple combination of zanamivir, clarithromycin and flufenamic acid (FFA) in the treatment of influenza virus A(H1N1) infection. An in vitro cell protection assay and a multiple-cycle growth assay showed that the antiviral activity of zanamivir was enhanced when combined with clarithromycin or FFA. A mouse challenge model was used here for the evaluation of the in vivo efficacy of the triple combination treatment...
May 7, 2018: Archives of Virology
Penelope J Hallett, Mylene Huebecker, Oeystein R Brekk, Elizabeth B Moloney, Emily M Rocha, David A Priestman, Frances M Platt, Ole Isacson
Aging is the predominant risk factor for both genetic and sporadic Parkinson's disease (PD). The majority of PD cases are nonfamilial, and the connection between aging and PD-associated genes is not well understood. Haploinsufficiency of the GBA gene, leading to a reduction in glucocerebrosidase (GCase) activity, is one of the most common genetic risk factors for PD. Furthermore, GCase activity is also reduced in brain regions of sporadic PD patients, with a corresponding accumulation of its glycosphingolipid (GSL) substrates...
March 29, 2018: Neurobiology of Aging
Anne Fougerat, Xuefang Pan, Victoria Smutova, Nikolaus Heveker, Christopher W Cairo, Tarik Issad, Bruno Larrivée, Jeffrey A Medin, Alexey V Pshezhetsky
OBJECTIVES: Neuraminidase 1 (NEU1) cleaves terminal sialic acids of glycoconjugates during lysosomal catabolism. It also modulates the structure and activity of cellular surface receptors affecting diverse pathways. Previously we demonstrated that NEU1 activates the insulin receptor (IR) and that NEU1-deficient CathAS190A-Neo mice (hypomorph of the NEU1 activator protein, cathepsin A/CathA) on a high-fat diet (HFD) develop hyperglycaemia and insulin resistance faster than wild-type animals...
April 21, 2018: Molecular Metabolism
K Okuya, A Matsuu, T Kawabata, F Koike, M Ito, T Furuya, A Taneno, S Akimoto, E Deguchi, M Ozawa
Swine influenza viruses (SIVs) are important not only for pig farming, but also for public health. In fact, pandemic A(H1N1) 2009 viruses [A(H1N1)pdm09] were derived from SIVs. Therefore, timely characterization of locally circulating SIVs is necessary for understanding the global status of SIVs. To genetically characterize SIVs circulating in Japanese pig populations, we isolated 24 SIVs of three subtypes (17 H1N1, four H1N2 and three H3N2 strains) from 14 pig farms in Japan from 2013 to 2016. Genetic analyses revealed that the haemagglutinin (HA) and neuraminidase (NA) genes of the 17 H1N1 and the HA gene of one H1N2, A/swine/Aichi/02/2016 (H1N2), SIVs belonged to the A(H1N1)pdm09 lineage...
May 6, 2018: Transboundary and Emerging Diseases
Rusheng Zhang, Dong Yao, Jingfang Chen, Wen Ye, Xinhua Ou, Tianmu Chen, Biancheng Sun
As of Aug 25, 2017, 17 incidences of human infection and 6 deaths due to the novel H5N6 virus have been reported in China. Genetic analysis of the viral genome revealed that this reassortant virus is highly pathogenic to poultry, and that the virus has a risk of transmission to humans. Accordingly, the development of a rapid, sensitive, and specific molecular diagnostic assay is critical for public health. In this study, a real-time reverse-transcription PCR (RT-PCR) assay was developed to specifically detect the novel H5N6 virus, with primer pairs targeting the hemagglutinin and neuraminidase gene sequences of this virus...
May 2, 2018: Journal of Virological Methods
Ema T Crooks, Samantha L Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Rӓmisch, Sergey Menis, William R Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R Mascola, Gestur Vidarsson, James M Binley
The extensive glycosylation of HIV-1 envelope (Env) glycoprotein leaves few glycan-free holes large enough to admit broadly neutralizing antibodies (bnAb). Consequently, most bnAbs must inevitably make some glycan contacts and avoid clashes with others. To investigate how Env glycan maturation regulates HIV sensitivity to bnAbs, we modified HIV-1 pseudovirus (PV) using various glycoengineering (GE) tools. Promoting the maturation of α-2,6 sialic acid (SA) glycan termini increased PV sensitivity to two bnAbs that target the V2 apex and one to the interface between Env surface gp120 and transmembrane gp41 subunits, typically by up to 30-fold...
May 2, 2018: PLoS Pathogens
Naomi Bradbury, Jonathan Nguyen-Van-Tam, Wei Shen Lim
BACKGROUND: The value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo-controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza. METHODS: Senior clinicians (n = 50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey...
May 2, 2018: BMC Health Services Research
Tomoko Kuwahara, Emi Takashita, Seiichiro Fujisaki, Masayuki Shirakura, Kazuya Nakamura, Noriko Kishida, Hitoshi Takahashi, Noriko Suzuki, Yoshihiro Kawaoka, Shinji Watanabe, Takato Odagiri
Antigenic changes in the hemagglutinin protein of recent A(H3N2) viruses are often induced when these viruses adapt to their egg hosts. We have successfully isolated an egg-adapted influenza A(H3N2) virus, A/Saitama/103/2014, without amino acid substitutions in the antigenic sites of its hemagglutinin protein but multiple substitutions in its neuraminidase protein by serial egg passages of a cell-propagated virus. Antigenic analysis of this egg-adapted A/Saitama/103/2014 virus indicated that its antigenicity did not change from the WHO prototype cell-propagated vaccine virus, A/Hong Kong/4801/2014...
April 27, 2018: Japanese Journal of Infectious Diseases
Momena Habib, Tahir Yaqub, Jawad Nazir, Wasim Shehzad, Aziz-Ul-Rahman, Tayyebah Sohail, Nadia Mukhtar, Arsalan Mehboob, Muhammad Munir, Muhammad Zubair Shabbir
Given the global evolutionary dynamics of Newcastle disease viruses (NDVs), it is imperative to continue extensive surveillance, routine monitoring and characterization of isolates originating from natural reservoirs (waterfowls). In this report, we isolated and characterized two virulent NDV strains from clinically healthy mallard (Anas platyrhynchos). Both isolates had a genome of 15,192 nucleotides encoding six genes in an order of 3´-NP-P-M-F-HN-L-5´. The biological characteristics (mean death time: 49...
April 30, 2018: Archives of Virology
Yu-Pin Liu, Dong-Hun Lee, Li-Hsuan Chen, Yu-Ju Lin, Wan-Chan Li, Shu-Chia Hu, Yen-Ping Chen, David E Swayne, Ming-Shiuh Lee
A H5N6 highly pathogenic avian influenza virus (HPAIV) was detected in a black-faced spoonbill (Platalea minor) found dead in Taiwan during December 2017. Genome sequencing and phylogenetic analyses suggest the hemagglutinin gene belongs to H5 clade Group B. All genes except neuraminidase gene shared high levels of nucleotide identity with H5N8 HPAIV identified from Europe during 2016-2017. Genetically similar H5N6 HPAIV also identified from Japan during November 2017. Enhanced surveillance is required in this region...
April 26, 2018: Infection, Genetics and Evolution
Yana Sharapova, Dmitry Suplatov, Vytas Švedas
Neuraminidase A (NanA) of the pathogen Streptococcus pneumoniae cleaves receptors of the human respiratory epithelial surface during bacterial colonization. The full-size structure of NanA that contains one lectin and one catalytic domain within a single polypeptide chain remains unresolved. Both domains are crucial for the microorganism's virulence and considered as promising antimicrobial targets. Methods of bioinformatics and molecular dynamics have been implemented to model NanA's structure and study interaction between the lectin and catalytic domains in three neuraminidases NanA, NanB, and NanC from Streptococcus pneumoniae...
April 28, 2018: FEBS Journal
Mei-Fang Huang, Yi-Reng Lin, Yu-Tzu Chang, Yow-Ling Shiue, Shih-Shin Liang
Oseltamivir phosphate (OP) is the first line therapy for influenza, and its primary metabolite oseltamivir carboxylate (OC) is the active agent via inhibition of neuraminidase of influenza virus. Dosages of OP and OC might affect human causing nausea and vomiting and it is therefore necessary to evaluate their toxicity and safety. The separation system: liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful technique to monitor OP and OC. However, quantification of OP and OC needs isotopic analogs as internal standards to monitor the stability of the sample pretreatment procedures and instruments...
April 4, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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