Establishment and lineage replacement of H6N2 influenza viruses in domestic ducks in Southern China (2000-2007)

Multiple reassortant events between different subtypes of endemic avian influenza viruses have increased the genomic diversity of influenza viruses circulating in poultry in southern China. Gene exchange from the natural gene pool to poultry has contributed to this increase in genetic diversity. However, the role of domestic ducks as an interface between the natural gene pool and terrestrial poultry in the influenza ecosystem has not been well defined. Here we phylogenetically and antigenically analyzed 206 H6 viruses isolated from domestic ducks from 2000 to 2007 in southern China which contains the largest population of domestic ducks in the world. Three distinct H6 lineages were identified. Group 1 contained the majority of isolates with a single internal gene complex and was endemic in domestic ducks in Guangdong from the late 1990’s to 2005. Group 2 was derived from reassortment events in which the surface genes of Group 1 viruses were replaced by novel H6 and N2 genes, which appeared in 2004 and gradually replaced the Group 1 viruses and became the predominant H6N2 variant after 2005. Epidemiological and genetic findings also show that the Group 2 viruses started to disseminate from the coastal regions to inland provinces and was also introduced into terrestrial poultry. The Group 3 H6 viruses represent part of an influenza gene pool that undergoes frequent gene exchange with different subtypes. Our study revealed that gene exchanges between viruses from domestic duck and migratory duck occurred throughout the surveillance period. These findings suggest that domestic duck in southern China mediate the interaction of viruses between different gene pools and facilitate the generation of novel influenza variants circulating in poultry.postprintThe 4th Annual CEIRS Network Meeting, Fairport, NY., 3-5 August 2010. In Abstracts of the 4th Annual CEIRS Network Meeting, 2010, p. 2

Conditional value-at-risk for water management in Lake Burley Griffin

Copyright © Australian Mathematical SocietyAs the centrepiece of Canberra, Lake Burley Griffin provides the setting for buildings of national importance and a venue for aquatic recreation while, as part of the Molonglo River, the lake has a role in the ecological processes of its broader setting. For the purposes of recreation and landscape a constant water level is preferred: the management plan requires the lake to be maintained at a prescribed normal level. In years of low rainfall this requirement could conflict with the water demands of other users. Episodes of high rainfall may also require compromise between competing objectives. For example, drawdown of lake levels for flood mitigation could impact on the lake's recreational and amenity values and the spill may not be a good use of water. Conditional Value at Risk, a risk measure developed by the financial industry for portfolio management, is defined as the expected loss given that some loss threshold is exceeded. Here, Conditional Value at Risk is applied as decision support for strategic planning and day-to-day operational problems in the hydraulic management of Lake Burley Griffin.R. B. Webby, J. Boland, P. G. Howlett, A. V. Metcalfe, T. Srithara

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

Age-Induced Diminution of Free Radical Scavenging Capacity in Bee Pollens and the Contribution of Constituent Flavonoids

Bee-collected pollen (“bee pollen”) is promoted as a health food with a wide range of nutritional and therapeutic properties. The objective of the current study is to evaluate the contribution made through the free radical scavenging capability of bee-collected floval pollens by their flavonoid/phenolics constituents, and to determine whether this capability is affected by aging. The free radical scavenging effectiveness of a bee pollen (EC50) as measured by the DPPH method is shown to be determined by the nature and levels of the constituent floral pollens, which can be assayed via their phenolics profiles by HPLC. Each pure floral pollen has been found to possess a consistent EC50 value, irrespective of its geographic origin or date of collection, and the EC50 value is determined to a large extent (ca. 50%) by the nature and the levels of the pollen's flavonoids and phenolic acids. Non-phenolic antioxidants, possibly proteins, account for the balance of the activity. Pollen aging over 3 years is demonstrated to reduce the free radical scavenging activity by up to 50% in the most active floral pollens, which tend to contain the highest levels of flavonoids/phenolic acids. It is suggested that the freshness of a bee pollen may be determined from its free radical scavenging capacity relative to that of fresh bee pollen containing the same floral pollen mix

The celebritization of indigenous activism:Tame Iti as media figure

In recent years, a number of indigenous activists have gained celebrity status in ways that carry interesting implications for contemporary cultural politics. This article focuses on the celebrification of Tame Iti, arguably Aotearoa/New Zealand’s best-known Māori activist, within a wider cultural context characterized by intensifying media convergence, an expanding politics of decolonization, and the continuing elaboration of global indigenous mediascapes, including the Māori Television Service. We draw on forms of conjunctural analysis to explore how wider historical forces and social dynamics come to be embodied in particular flesh and blood individuals, who are thereby constituted as resonant media figures, who operate as both objects and agents of struggle, and who at once intervene in and shape, while also being shaped by, key terrains of contemporary discourse and cultural politics

Airway CD8+CD8^+ T Cells Induced by Pulmonary DNA Immunization Mediate Protective Anti-Viral Immunity

Vaccination strategies for protection against a number of respiratory pathogens must induce T-cell populations in both the pulmonary airways and peripheral lymphoid organs. In this study, we show that pulmonary immunization using plasmid DNA formulated with the polymer polyethyleneimine (PEI-DNA) induced antigen-specific $CD8^+$ T cells in the airways that persisted long after antigen local clearance. The persistence of the cells was not mediated by local lymphocyte proliferation or persistent antigen presentation within the lung or airways. These vaccine-induced $CD8^+$ T cells effectively mediated protective immunity against respiratory challenges with vaccinia virus and influenza virus. Moreover, this protection was not dependent upon the recruitment of T cells from peripheral sites. These findings demonstrate that pulmonary immunization with PEI-DNA is an efficient approach for inducing robust pulmonary $CD8^+$ T-cell populations that are effective at protecting against respiratory pathogens

Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine

Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions

Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D

<p>Abstract</p> <p>Background</p> <p>Surfactant protein D (SP-D) plays an important role in innate defense against influenza A viruses (IAVs) and other pathogens.</p> <p>Methods</p> <p>We tested antiviral activities of recombinant human SP-D against a panel of IAV strains that vary in glycosylation sites on their hemagglutinin (HA). For these experiments a recombinant version of human SP-D of the Met11, Ala160 genotype was used after it was characterized biochemically and structurally.</p> <p>Results</p> <p>Oligosaccharides at amino acid 165 on the HA in the H3N2 subtype and 104 in the H1N1 subtype are absent in collectin-resistant strains developed <it>in vitro </it>and are important for mediating antiviral activity of SP-D; however, other glycans on the HA of these viral subtypes also are involved in inhibition by SP-D. H3N2 strains obtained shortly after introduction into the human population were largely resistant to SP-D, despite having the glycan at 165. H3N2 strains have become steadily more sensitive to SP-D over time in the human population, in association with addition of other glycans to the head region of the HA. In contrast, H1N1 strains were most sensitive in the 1970s–1980s and more recent strains have become less sensitive, despite retaining the glycan at 104. Two H5N1 strains were also resistant to inhibition by SP-D. By comparing sites of glycan attachment on sensitive vs. resistant strains, specific glycan sites on the head domain of the HA are implicated as important for inhibition by SP-D. Molecular modeling of the glycan attachment sites on HA and the carbohydrate recognition domain of SPD are consistent with these observations.</p> <p>Conclusion</p> <p>Inhibition by SP-D correlates with presence of several glycan attachment sites on the HA. Pandemic and avian strains appear to lack susceptibility to SP-D and this could be a contributory factor to their virulence.</p

Construction and immunogenicity evaluation of recombinant influenza A viruses containing chimeric hemagglutinin genes derived from genetically divergent influenza A H1N1 subtype viruses

Citation: McCormick, K., Jiang, Z., Zhu, L., Lawson, S. R., Langenhorst, R., Ransburgh, R., . . . Fang, Y. (2015). Construction and immunogenicity evaluation of recombinant influenza A viruses containing chimeric hemagglutinin genes derived from genetically divergent influenza A H1N1 subtype viruses. Plos One, 10(6). doi:10.1371/journal.pone.0127649Background and Objectives: Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Methods and Results: Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV- 129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV- 129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. Conclusion: This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines. © 2015 McCormick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhe- sus macaques. To test them as potential vaccines, we engineered RD and SC ver- sions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro. SC-Ad pro- duced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influ- enza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as “needle-free” mucosal vaccines