Selection of H3 avian influenza viruses with SAα2,6Gal receptor specificity in pigs

AbstractAvian influenza viruses possess hemagglutinin (HA) which preferentially bind to the sialic acid α2,3-galactose sialyloligosaccharides (SAα2,3Gal) receptor. In contrast, human influenza viruses bind to sialic acid α2,6-galactose sialyloligosaccharides (SAα2,6Gal). The A/Hong Kong/68 (H3N2) virus preferentially binds to SAα2,6Gal, although its HA gene was derived from an avian influenza virus strain. To elucidate the mechanisms behind acquisition of binding specificity for the human-type receptor, the avian influenza virus, A/duck/Hokkaido/5/77 (H3N2), which carries the HA with SAα2,3Gal receptor specificity, was consecutively passaged in pigs. Viruses that preferentially bind to the SAα2,6Gal receptor were predominantly recovered from the nasal swabs of pigs after three passages. The present results indicate that avian influenza viruses can acquire the potential to infect humans after multiple infections in a pig population. Intensive surveillance of swine influenza is, thus, important for the preparedness for the future pandemics

Cement generations and diagenetic history of the upper Ordovician Cliefden Caves Limestone Group of New South Wales, Australia

Diagenetic features of the upper Ordovician (Caradocian) Cliefden Caves Limestone Group (N. S. W., Australia) were studied by the cathodoluminescence (CL) method, and their relation with depositional environments was discussed. The Cliefden Caves Limestone Group was deposited on a shallow marine carbonate platform developed on a volcanic island. The limestone succession reveals intertidal-subtidal lithofacies and consists of the Fossil Hill, Belubula, and Vandon Limestones, in ascending order. The Fossil Hill Limestone mostly consists of bedded limestone rich in brachiopods and sedentary organisms. The Belubula Limestone is a typical Middle-Upper Ordovician peritidal succession with syn-depositional dolomite and silicified fossil grains. The Vandon Limestone consists of fossiliferous stratified limestone occasionally containing red brown argillaceous limestone beds. The Cliefden Caves Limestone Group was subjected to various diagenetic processes. The investigation of CL is the best or only method to differentiate the diagenetic products. There are at least three cementation stages and a dissolution stage. The cements of the first stage are mainly dull fine-grained (10-30 µm) calcite crystals fringing inter- and intra-granular porosity, which typically indicate a marine phreatic environment. In some specimens of the Belubula Limestone, cement of the first generation exhibits meniscus fabrics suggesting precipitation in a marine vadose environment. The dissolution formed both molds of aragonitic skeletal grains and fabric-unrelated void spaces which can exceed several cm in diameter. Lack of the first generation cement within the dissolution voids indicates that the dissolution postdated the marine cementation. After the dissolution stage, the second cementation precipitated granular calcite crystals composed of non-luminescence, dull, and bright zones in the peripheral order. The relative thickness of non-luminescence and bright zones probably related with a redox condition during their diagenesis. The last generation of cements formed in a deep burial environment, is normally dull and filled almost all remained porosity. This diagenetic history fits to the change of depositional environment which may have been controlled by both of local and global environmental settings

Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.

Human cases of H7N9 influenza A virus infection have been increasing since 2013. The first choice of treatment for influenza is neuraminidase (NA) inhibitors (NAIs), but there is a concern that NAI-resistant viruses are selected in the presence of NAIs. In our previous study, an H7N9 virus carrying AA substitution of threonine (T) for isoleucine (I) at residue 222 in NA (NA222T, N2 numbering) and an H7N9 virus carrying AA substitution of lysine (K) for arginine (R) at residue 292 in NA (NA292K, N2 numbering) were found in different macaques that had been infected with A/Anhui/1/2013 (H7N9) and treated with NAIs. In the present study, the variant with NA292K showed not only resistance to NAIs but also lower replication activity in MDCK cells than did the virus with wild-type NA, whereas the variant with NA222T, which was less resistant to NAIs, showed replication activity similar to that of the wild-type virus. Next, we examined the pathogenicity of these H7N9 NAI-resistant viruses in macaques. The variants caused clinical signs similar to those caused by the wild-type virus with similar replication potency. However, the virus with NA292K was replaced within 7 days by that with NA292R (same as the wild-type) in nasal samples from macaques infected with the virus with NA292K, i.e. the so-called revertant (wild-type virus) became dominant in the population in the absence of an NAI. These results suggest that the clinical signs observed in macaques infected with the NA292K virus are caused by the NA292K virus and the NA292R virus and that the virus with NA292K may not replicate continuously in the upper respiratory tract of patients without treatment as effectively as the wild-type virus

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels

Background: Emulsions stabilized by colloidal particles are known as Pickering emulsions. To date, soft microgel particles as well as inorganic and organic particles have been utilized as Pickering emulsifiers. Although cyclodextrin (CD) works as an attractive emulsion stabilizer through the formation of a CD–oil complex at the oil–water interface, a high concentration of CD is normally required. Our research focuses on an effective Pickering emulsifier based on a soft colloidal CD polymer (CD nanogel) with a unique surface-active property.Results: CD nanogels were prepared by crosslinking heptakis(2,6-di-O-methyl)-β-cyclodextrin with phenyl diisocyanate and subsequent immersion of the resulting polymer in water. A dynamic light scattering study shows that primary CD nanogels with 30–50 nm diameter assemble into larger CD nanogels with 120 nm diameter by an increase in the concentration of CD nanogel from 0.01 to 0.1 wt %. The CD nanogel has a surface-active property at the air–water interface, which reduces the surface tension of water. The CD nanogel works as an effective Pickering emulsion stabilizer even at a low concentration (0.1 wt %), forming stable oil-in-water emulsions through interfacial adsorption by the CD nanogels.Conclusion: Soft CD nanogel particles adsorb at the oil–water interface with an effective coverage by forming a strong interconnected network and form a stable Pickering emulsion. The adsorption property of CD nanogels on the droplet surface has great potential to become new microcapsule building blocks with porous surfaces. These microcapsules may act as stimuli-responsive nanocarriers and nanocontainers

Experimental infection of highly and low pathogenic avian influenza viruses to chicken's, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission

Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. (C) 2015 Elsevier B.V. All rights reserved

Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010-2011 winter season in Japan

H5N1 highly pathogenic avian influenza virus (HPAIV) was reintroduced and caused outbreaks in chickens in 2010-2011 winter season in Japan, which had been free from highly pathogenic avian influenza (HPAI) since 2007 when HPAI outbreaks occurred and were controlled. On October 14, 2010 at Lake Ohnuma, Wakkanai, the northernmost part of Hokkaido, Japan, H5N1 HPAIVs were isolated from fecal samples of ducks flying from their nesting lakes in Siberia. Since then, in Japan, H5N1 HPAIVs have been isolated from 63 wild birds in 17 prefectures and caused HPAI outbreaks in 24 chicken farms in 9 prefectures by the end of March in 2011. Each of these isolates was genetically closely related to the HPAIV isolates at Lake Ohnuma, and those in China, Mongolia, Russia, and Korea, belonging to genetic clade 2.3.2.1. In addition, these isolates were genetically classified into 3 groups, suggesting that the viruses were transmitted by migratory water birds through at least 3 different routes from their northern territory to Japan. These isolates were antigenic variants, which is consistent with selection in poultry under the immunological pressure induced by vaccination. To prevent the perpetuation of viruses in the lakes where water birds nest in summer in Siberia, prompt eradication of HPAIVs in poultry is urgently needed in Asian countries where HPAI has not been controlled

Cyclodextrin Polymers as Highly Effective Adsorbents for Removal and Recovery of Polychlorobiphenyl (PCB) Contaminants in Insulating Oil

A total of 179 countries (parties) ratified the Stockholm Convention on persistent organic pollutants (POPs) and agreed to destroy polychlorobiphenyls (PCBs) and develop a sound management plan by 2028. Currently, still 3 million tons of PCB-contaminated oil and equipment need to be managed under the Stockholm Convention. Thus, the development of a facile and environmentally benign method to treat large amounts of oil stockpiles contaminated with PCBs is a crucial subject. Herein, we report that cyclodextrin (CD) polymers, which are easily prepared by cross-linking the renewable cyclic oligosaccharide γ-cyclodextrin (γ-CD) with dibasic acid dichlorides, are a new selective and powerful adsorbent to remove PCB contaminants in oil. When PCB (100 ppm)-contaminated oil was passed through a column packed with the terephthaloyl-cross-linked γ-CD polymer (TP-γ-CD polymer) at 80–110 °C, the PCB contaminants were completely removed from the oil. Additionally, methyl esterification of the free carboxylic groups of the TP-γ-CD polymer enabled the complete recovery of the PCBs adsorbed on the polymer (with >99.9% recovery efficiency) by simply washing with acetone. The methyl-esterified TP-γ-CD polymer could be recycled at least 10 times for PCB adsorption without any loss in the adsorption capability. These results revealed that the γ-CD polymers can function as highly effective and powerful adsorbents for the removal and recovery of PCBs from PCB-contaminated oil and, thus, significantly contribute to the protection of the global environment

Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates

The number of patients infected with H7N9 influenza virus has been increasing since 2013. We examined the efficacy of neuraminidase (NA) inhibitors and the efficacy of a vaccine against an H7N9 influenza virus, A/Anhui/1/2013 (H7N9), isolated from a patient in a cynomolgus macaque model. NA inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with R289K or I219T in NA [residues 289 and 219 in N9 of A/Anhui/1/2013 (H7N9) correspond to 292 and 222 in N2, respectively] in three of the six treated macaques, whereas subcutaneous immunization of an inactivated vaccine derived from A/duck/Mongolia/119/2008 (H7N9) prevented propagation of A/Anhui/1/2013 (H7N9) in all vaccinated macaques. The percentage of macaques in which variant H7N9 viruses with low sensitivity to the NA inhibitors were detected was much higher than that of macaques in which variant H5N1 highly pathogenic influenza virus was detected after treatment with one of the NA inhibitors in our previous study. The virus with R289K in NA was reported in samples from human patients, whereas that with I219T in NA was identified for the first time in this study using macaques, though no variant H7N9 virus was reported in previous studies using mice. Therefore, the macaque model enables prediction of the frequency of emerging H7N9 virus resistant to NA inhibitors in vivo. Since H7N9 strains resistant to NA inhibitors might easily emerge compared to other influenza viruses, monitoring of the emergence of variants is required during treatment of H7N9 influenza virus infection with NA inhibitors