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

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

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

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

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

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.published_or_final_versio

Trivalent live attenuated influenza-simian immunodeficiency virus vaccines: efficacy and evolution of cytotoxic T lymphocyte escape in macaques.

There is an urgent need for a human immunodeficiency virus (HIV) vaccine that induces robust mucosal immunity. CD8+ cytotoxic T lymphocytes (CTLs) apply substantial antiviral pressure, but CTLs to individual epitopes select for immune escape variants in both HIV in humans and SIV in macaques. Inducing multiple simian immunodeficiency virus (SIV)-specific CTLs may assist in controlling viremia. We vaccinated 10 Mane-A1*08401+ female pigtail macaques with recombinant influenza viruses expressing three Mane-A1*08401-restricted SIV-specific CTL epitopes and subsequently challenged the animals, along with five controls, intravaginally with SIVmac251. Seroconversion to the influenza virus vector resulted and small, but detectable, SIV-specific CTL responses were induced. There was a boost in CTL responses after challenge but no protection from high-level viremia or CD4 depletion was observed. All three CTL epitopes underwent a coordinated pattern of immune escape during early SIV infection. CTL escape was more rapid in the vaccinees than in the controls at the more dominant CTL epitopes. Although CTL escape can incur a &quot;fitness&quot; cost to the virus, a putative compensatory mutation 20 amino acids upstream from an immunodominant Gag CTL epitope also evolved soon after the primary CTL escape mutation. We conclude that vaccines based only on CTL epitopes will likely be undermined by rapid evolution of both CTL escape and compensatory mutations. More potent and possibly broader immune responses may be required to protect pigtail macaques from SIV. <br /

The climatic significance of Late Ordovician-early Silurian black

The Ordovician-Silurian transition (455-430 Ma) is characterized by repeated climatic perturbations, concomitant with major changes in the global oceanic redox state best exemplified by the periodic deposition of black shales. The relationship between the climatic evolution and the oceanic redox cycles, however, remains largely debated. Here, using an ocean-atmosphere general circulation model accounting for ocean biogeochemistry (MITgcm), we investigate the mechanisms responsible for the burial of organic carbon immediately before, during and right after the latest Ordovician Hirnantian (445-444 Ma) glacial peak. Our results are compared with recent sedimentological and geochemical data. We show that the late Katian time slice (445 Ma), typified by the deposition of black shales at tropical latitudes, represents an unperturbed oceanic state, with regional organic carbon burial driven by the surface primary productivity. During the Hirnantian, our experiments predict a global oxygenation event, in agreement with the disappearance of the black shales in the sedimentary record. This suggests that deep-water burial of organic matter may not be a tenable triggering factor for the positive carbon excursion reported at that time. Our simulations indicate that the perturbation of the ocean circulation induced by the release of freshwater, in the context of the post-Hirnantian deglaciation, does not sustain over sufficiently long geological periods to cause the Rhuddanian (444 Ma) oceanic anoxic event. Input of nutrients to the ocean, through increased continental weathering and the leaching of newly-exposed glaciogenic sediments, may instead constitute the dominant control on the spread of anoxia in the early Silurian

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