H9N2 Influenza A Viruses from Poultry in Asia Have Human Virus-like Receptor Specificity

AbstractH9N2 influenza A viruses are currently widespread in chickens, quail, and other poultry in Asia and have caused a few cases of influenza in humans. In this study, we found that H9N2 viruses from Hong Kong live bird markets have receptor specificity similar to that of human H3N2 viruses. In addition, the neuraminidase of poultry H9N2 viruses has mutations in its hemadsorbing site, a characteristic resembling that of human H2N2 and H3N2 viruses but differing from that of other avian viruses. Peculiar features of surface glycoproteins of H9N2 viruses from Hong Kong suggest an enhanced propensity for introduction into humans and emphasize the importance of poultry in the zoonotic transmission of influenza viruses

Nano-optical observation of cascade switching in a parallel superconducting nanowire single photon detector

The device physics of parallel-wire superconducting nanowire single photon detectors is based on a cascade process. Using nano-optical techniques and a parallel wire device with spatially-separate pixels we explicitly demonstrate the single- and multi-photon triggering regimes. We develop a model for describing efficiency of a detector operating in the arm-trigger regime. We investigate the timing response of the detector when illuminating a single pixel and two pixels. We see a change in the active area of the detector between the two regimes and find the two-pixel trigger regime to have a faster timing response than the one-pixel regime.Comment: 11 pages, 2 figure

On some fundamental results about higher-rank graphs and their C*-algebras

Results of Fowler and Sims show that every k-graph is completely determined by its k-coloured skeleton and collection of commuting squares. Here we give an explicit description of the k-graph associated to a given skeleton and collection of squares and show that two k-graphs are isomorphic if and only if there is an isomorphism of their skeletons which preserves commuting squares. We use this to prove directly that each k-graph {\Lambda} is isomorphic to the quotient of the path category of its skeleton by the equivalence relation determined by the commuting squares, and show that this extends to a homeomorphism of infinite-path spaces when the k-graph is row finite with no sources. We conclude with a short direct proof of the characterisation, originally due to Robertson and Sims, of simplicity of the C*-algebra of a row-finite k-graph with no sources.Comment: 21 pages, two pictures prepared using TiK

CK2beta gene silencing increases cell susceptibility to influenza A virus infection resulting in accelerated virus entry and higher viral protein content

Background: Influenza A virus (IVA) exploits diverse cellular gene products to support its replication in the host. The significance of the regulatory (β) subunit of casein kinase 2 (CK2β) in various cellular mechanisms is well established, but less is known about its potential role in IVA replication. We studied the role of CK2β in IVA-infected A549 human epithelial lung cells. Results: Activation of CK2β was observed in A549 cells during virus binding and internalization but appeared to be constrained as replication began. We used small interfering RNAs (siRNAs) targeting CK2β mRNA to silence CK2β protein expression in A549 cells without affecting expression of the CK2α subunit. CK2β gene silencing led to increased virus titers, consistent with the inhibition of CK2β during IVA replication. Notably, virus titers increased significantly when CK2β siRNA-transfected cells were inoculated at a lower multiplicity of infection. Virus titers also increased in cells treated with a specific CK2 inhibitor but decreased in cells treated with a CK2β stimulator. CK2β absence did not impair nuclear export of viral ribonucleoprotein complexes (6 h and 8 h after inoculation) or viral polymerase activity (analyzed in a minigenome system). The enhancement of virus titers by CK2β siRNA reflects increased cell susceptibility to influenza virus infection resulting in accelerated virus entry and higher viral protein content. Conclusion: This study demonstrates the role of cellular CK2β protein in the viral biology. Our results are the first to demonstrate a functional link between siRNA-mediated inhibition of the CK2β protein and regulation of influenza A virus replication in infected cells. Overall, the data suggest that expression and activation of CK2β inhibits influenza virus replication by regulating the virus entry process and viral protein synthesis. © 2008 Marjuki et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Reassortment and Interspecies Transmission of North American H6N2 Influenza Viruses

AbstractH6N2 influenza viruses were isolated from California chickens in 2000 and 2001. Here we report the characterization of these H6N2 viruses, one of the few descriptions of non-H5, non-H7 subtype influenza viruses in this host. The H6N2 viruses were nonpathogenic in experimentally infected chickens and could be divided into three genotypes. All three genotypes of virus had similar surface glycoproteins and all contained an 18 amino acid deletion in the neuraminidase, a characteristic of other chicken influenza viruses. Differences were apparent, however, in the complement of replicative protein genes between the genotypes. The presence of multiple H6N2 genotypes suggests that independent transmission and/or reassortment events may have taken place between aquatic bird and chicken influenza viruses

Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade

Influenza viruses replicate within the nucleus of infected cells. Viral genomic RNA, three polymerase subunits (PB2, PB1, and PA), and the nucleoprotein (NP) form ribonucleoprotein complexes (RNPs) that are exported from the nucleus late during the infectious cycle. The virus-induced Raf/MEK/ERK (MAPK) signal cascade is crucial for efficient virus replication. Blockade of this pathway retards RNP export and reduces virus titers. Hemagglutinin (HA) accumulation and its tight association with lipid rafts activate ERK and enhance localization of cytoplasmic RNPs. We studied the induction of MAPK signal cascade by two seasonal human influenza A viruses A/HK/218449/06 (H3N2) and A/HK/218847/06 (H1N1) that differed substantially in their replication efficiency in tissue culture. Infection with H3N2 virus, which replicates efficiently, resulted in higher HA expression and its accumulation on the cell membrane, leading to substantially increased activation of MAPK signaling compared to that caused by H1N1 subtype. More H3N2-HAs were expressed and accumulated on the cell membrane than did H1N1-HAs. Viral polymerase genes, particularly H3N2-PB1 and H3N2-PB2, were observed to contribute to increased viral polymerase activity. Applying plasmid-based reverse genetics to analyze the role of PB1 protein in activating HA-induced MAPK cascade showed that recombinant H1N1 virus possessing the H3N2-PB1 (rgH1N1/H3N2-PB1) induced greater ERK activation, resulting in increased nuclear export of the viral genome and higr virus titers. We conclude that enhanced viral polymerase activity promotes the replication and transcription of viral RNA leading to increased accumulation of HA on the cell surface and thereby resulting in an upregulation of the MAPK cascade and more efficient nuclear RNP-export as well as virus production

Fluoride-containing bioactive glasses: Effect of glass design and structure on degradation, pH and apatite formation in simulated body fluid

NOTICE: this is the author’s version of a work that was accepted for publication in Acta Biomaterialia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Acta Biomaterialia, [VOL 6, ISSUE 8, (2010)] DOI: 10.1016/j.actbio.2010.01.04

Avian influenza viruses in Korean live poultry markets and their pathogenic potential

AbstractWe surveyed live-poultry markets in Korea in 2003 and isolated 9 H9N2, 6 H3N2, and 1 H6N1 influenza viruses. Antigenic and phylogenetic analyses showed that all 9 H9N2 isolates were of A/Chicken/Korea/25232-96006/96-like lineage (which caused disease in chickens in Korea in 1996) but were different from H9N2 viruses of southeastern China. They had at least 4 genotypes and replicated in chickens but not in mice. The H3N2 and H6N1 viruses were new to Korea and were probably reassortants of avian influenza viruses from southeastern China and recent Korean H9N2 viruses. All 8 segments of the H3N2 viruses formed a single phylogenetic cluster with 99.1 to 100% homology. The H3N2 viruses replicated in chickens and mice without preadaptation, but the H6N1 virus did not. Our results show an increasingly diverse pool of avian influenza viruses in Korea that are potential pandemic influenza agents