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Influenza hemagglutinin

Klaudia Chrzastek, Dong-Hun Lee, Saad Gharaibeh, Aniko Zsak, Darrell R Kapczynski
Next-generation sequencing (NGS) technologies are a valuable tool to monitor changes in viral genomes and determine the genetic heterogeneity of viruses. In this study, NGS was applied to clinical poultry samples from Jordan to detect eleven H9N2 low pathogenic avian influenza viruses (LPAIV). All of the viruses tested belonged to Middle East A genetic group of G1 lineage. Deep sequencing demonstrated a high degree of heterogeneity of glutamine and leucine residues at position 226 in the hemagglutinin (HA) gene, which increases specificity to either avian or mammalian-type receptors...
March 7, 2018: Virology
Hitoshi Takahashi, Shiho Nagata, Takato Odagiri, Tsutomu Kageyama
The H5 subtype of highly pathogenic avian influenza (H5 HPAI) viruses is a threat to both animal and human public health and has the potential to cause a serious future pandemic in humans. Thus, specific and rapid detection of H5 HPAI viruses is required for infection control in humans. To develop a simple and rapid diagnostic system to detect H5 HPAI viruses with high specificity and sensitivity, we attempted to prepare monoclonal antibodies (mAbs) that specifically recognize linear epitopes in hemagglutinin (HA) of H5 subtype viruses...
March 7, 2018: Biochemical and Biophysical Research Communications
Shin-Hee Kim
Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza...
March 9, 2018: Viruses
Eugenia S Mardanova, Nikolai V Ravin
BACKGROUND: Influenza is a widely distributed infection that almost annually causes seasonal epidemics. The current egg-based platforms for influenza vaccine production are facing a number of challenges and are failing to satisfy the global demand in the case of pandemics due to the long production time. Recombinant vaccines are an alternative that can be quickly produced in high quantities in standard expression systems. METHODS: Plants may become a promising biofactory for the large-scale production of recombinant proteins due to low cost, scalability, and safety...
March 9, 2018: Current Pharmaceutical Design
Eita Sasaki, Haruka Momose, Yuki Hiradate, Ken J Ishii, Takuo Mizukami, Isao Hamaguchi
Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety...
December 2018: Journal of Immunotoxicology
I N Goronzy, R J Rawle, S G Boxer, P M Kasson
Influenza virus infects cells by binding to sialylated glycans on the cell surface. While the chemical structure of these glycans determines hemagglutinin-glycan binding affinity, bimolecular affinities are weak, so binding is avidity-dominated and driven by multivalent interactions. Here, we show that membrane spatial organization can control viral binding. Using single-virus fluorescence microscopy, we demonstrate that the sterol composition of the target membrane enhances viral binding avidity in a dose-dependent manner...
February 28, 2018: Chemical Science
Yanmin Wan, Guobin Kang, Chithra Sreenivasan, Lance Daharsh, Junfeng Zhang, Wenjin Fan, Dan Wang, Hideaki Moriyama, Feng Li, Qingsheng Li
Two lineages of Influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex (BRDC), one of the most commonly diagnosed causes of morbidity and mortality within the cattle industry. Furthermore, IDV can infect other economically important domestic livestock including pigs and has the potential to infect humans, which necessitates the need for an efficacious vaccine. In this study, we designed a DNA vaccine expressing consensus hemagglutinin-esterase-fusion (HEF) protein (FluD-Vax) and tested its protective efficacy against two lineages of IDV (D/OK and D/660) in guinea pigs...
March 7, 2018: Journal of Virology
Shin-Hee Kim, Siba K Samal
Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e...
February 22, 2018: Current Protocols in Microbiology
Christopher S Anderson, Sandra Ortega, Francisco A Chaves, Amelia M Clark, Hongmei Yang, David J Topham, Marta L DeDiego
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 6, 2018: Scientific Reports
Houshun Zhu, Andrew C Y Lee, Can Li, Winger W N Mak, Yetta Y Chen, Kwok-Hung Chan, Anna J X Zhang, Wai-Fong Fung, Rui-Qi Zhang, Yim-Fong Fung, Rosana W S Poon, Joy-Yan Lam, Sidney Tam, Ivan F N Hung, Honglin Chen, Kwok-Yung Yuen, Kelvin K W To
The 2017 Hong Kong influenza A(H3N2) summer season was unexpectedly severe. However, antigenic characterization of the 2017 circulating A(H3N2) viruses using ferret antisera did not show significant antigenic drift. We analyzed the hemagglutinin amino acid sequences of A(H3N2) virus circulating in Hong Kong in 2017, and found that viruses with hemagglutinin N121K substitution, which was rare before 2017, emerged rapidly and dominated in 2017 (52.4% of A[H3N2] virus in 2017 contains N121K substitution). Microneutralization assay using archived human sera collected from mid-2017 showed that the geometric mean microneutralization titer was 3...
March 6, 2018: Emerging Microbes & Infections
Adam Vigil, Angeles Estélles, Lawrence M Kauvar, Scott K Johnson, Ralph A Tripp, Michael Wittekind
Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single cell screening technology to identify rare monoclonal antibodies (mAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 mAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 mAbs, three exhibited low expression in a transient transfection system, four were neutralizers that bound to the HA head region, eleven were stalk-binding non-neutralizers, and five were stalk-binding neutralizers with four of these five representing unique antibody sequences...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Haixin Ai, Xuewei Wu, Mengyuan Qi, Li Zhang, Huan Hu, Qi Zhao, Jian Zhao, Hongsheng Liu
In recent years, new strains of influenza virus such as H7N9, H10N8, H5N6 and H5N8 had continued to emerge. There was an urgent need for discovery of new anti-influenza virus drugs as well as accurate and efficient large-scale inhibitor screening methods. In this study, we focused on six influenza virus proteins that could be anti-influenza drug targets, including neuraminidase (NA), hemagglutinin (HA), matrix protein 1 (M1), M2 proton channel (M2), nucleoprotein (NP) and non-structural protein 1 (NS1). Structure-based molecular docking was utilized to identify potential inhibitors for these drug targets from 13144 compounds in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform...
March 2, 2018: Interdisciplinary Sciences, Computational Life Sciences
Sander Boonstra, Jelle S Blijleven, Wouter H Roos, Patrick R Onck, Erik van der Giessen, Antoine M van Oijen
Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion...
March 1, 2018: Annual Review of Biophysics
Han Sol Lee, Ji Yun Noh, Joon Young Song, Hee Jin Cheong, Won Suk Choi, Hye Won Jeong, Seong-Heon Wie, Woo Joo Kim
Influenza A viruses are classified under the Orthomyxoviridae family, and consist of several subtypes, based on their hemagglutinin (HA) and neuraminidase (NA) composition. In some cases, reassortment of the 8 viral RNA segments may occur if different influenza viruses infect the same host, thereby generating new viral strains (antigenic shift). Mutations in the genes of influenza A viruses are enhanced by the absence of RNA proofreading enzymes; in particular, substitutions in the HA protein alter the viral antigenic epitopes sufficiently to avoid the host immune response (antigenic drift)...
February 28, 2018: Influenza and Other Respiratory Viruses
Susanne Liese, Roland R Netz
Multivalency achieves strong, yet reversible binding by the simultaneous formation of multiple weak bonds. It is a key interaction principle in biology and promising for the synthesis of high-affinity inhibitors of pathogens. We present a molecular model for the binding affinity of synthetic multivalent ligands onto multivalent receptors consisting of n receptor units arranged on a regular polygon. Ligands consist of geometrically matching rigid polygonal core to which monovalent ligand units are attached via flexible linker polymers, closely mimicking existing experimental designs...
February 23, 2018: ACS Nano
Fan Yang, Haibo Wu, Fumin Liu, Xiangyun Lu, Xiuming Peng, Nanping Wu
The H6 subtype avian influenza viruses (AIVs) possess the capacity for zoonotic transmission from avian species to humans. Establishment of a specific, rapid and sensitive method to screen H6 AIVs is necessary. Based on the conserved domain of the matrix and H6 AIV hemagglutinin genes, two TaqMan minor-groove-binder probes and multiplex real-time RT-PCR primers were designed in this study. The multiplex real-time RT-PCR assay developed in this study had high specificity and repeatability and a detection limit of 30 copies per reaction...
February 21, 2018: Archives of Virology
Daniela S Rajão, Daniel R Pérez
Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses...
2018: Frontiers in Microbiology
Aneth S Canale, Sergey V Venev, Troy W Whitfield, Daniel R Caffrey, Wayne A Marasco, Celia A Schiffer, Timothy F Kowalik, Jeffrey D Jensen, Robert W Finberg, Konstantin B Zeldovich, Jennifer P Wang, Daniel N A Bolon
The fitness effects of synonymous mutations can provide insights into biological and evolutionary mechanisms. We analyzed the experimental fitness effects of all single nucleotide mutations, including synonymous substitutions, at the beginning of the influenza A virus hemagglutinin (HA) gene. Many synonymous substitutions were deleterious in both bulk competition and for individually isolated clones. Investigating protein and RNA levels of a subset of individually expressed HA variants revealed that multiple biochemical properties contribute to the observed experimental fitness effects...
February 18, 2018: Journal of Molecular Biology
Derek R MacFadden, Allison McGeer, Taryn Athey, Stephen Perusini, Romy Olsha, Aimin Li, AliReza Eshaghi, Jonathan B Gubbay, William P Hanage
Adequacy of the current clinical definition of institutional influenza outbreaks is unclear. We performed a retrospective genome sequencing and epidemiologic analysis of institutional influenza outbreaks that occurred during the 2014-15 influenza season in Toronto, Canada. We sequenced the 2 earliest submitted samples positive for influenza A(H3N2) from each of 38 reported institutional outbreaks in long-term care facilities. Genome sequencing showed most outbreak pairs identified by using the current clinical definition were highly related...
March 2018: Emerging Infectious Diseases
Alessandra Gallinaro, Martina Borghi, Roberta Bona, Felicia Grasso, Laura Calzoletti, Laura Palladino, Serena Cecchetti, Maria Fenicia Vescio, Daniele Macchia, Valeria Morante, Andrea Canitano, Nigel Temperton, Maria Rita Castrucci, Mirella Salvatore, Zuleika Michelini, Andrea Cara, Donatella Negri
Viral vectors represent an attractive technology for vaccine delivery. We exploited the integrase defective lentiviral vector (IDLV) as a platform for delivering relevant antigens within the context of the ADITEC collaborative research program. In particular, Influenza virus hemagglutinin (HA) and nucleoprotein (NP) were delivered by IDLVs while H1N1 A/California/7/2009 subunit vaccine (HAp) with or without adjuvant was used to compare the immune response in a murine model of immunization. In order to maximize the antibody response against HA, both IDLVs were also pseudotyped with HA (IDLV-HA/HA and IDLV-NP/HA, respectively)...
2018: Frontiers in Immunology
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