The global circulation of seasonal influenza A (H3N2) viruses

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.     

Mapping the antigenic and genetic evolution of influenza virus

The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.     

Avian H5N1 influenza in cats

During the 2003 to 2004 outbreak of avian influenza A (H5N1) virus in Asia, there were anecdotal reports of fatal infection in domestic cats, although this species is considered resistant to influenza. We experimentally inoculated cats with H5N1 virus intratracheally and by feeding them virus-infected chickens. The cats excreted virus, developed severe diffuse alveolar damage, and transmitted virus to sentinel cats. These results show that domestic cats are at risk of disease or death from H5N1 virus, can be infected by horizontal transmission, and may play a role in the epidemiology of this virus.     

Host species barriers to influenza virus infections

Most emerging infectious diseases in humans originate from animal reservoirs; to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within individuals and host-host interactions, either within or between species, that affect transmission between individuals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions; however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.     

Newcastle disease virus outbreaks: Vaccine mismatch or inadequate application?

Newcastle disease (ND) is one of the most important diseases of poultry, and may cause devastating losses in the poultry industry worldwide. Its causative agent is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many countries maintain a stringent vaccination policy against ND, but there are indications that ND outbreaks can still occur despite intensive vaccination. It has been argued that this may be due to antigenic divergence between the vaccine strains and circulating field strains. Here we present the complete genome sequence of a highly virulent genotype VII virus (NL/93) obtained from vaccinated poultry during an outbreak of ND in the Netherlands in 1992-1993. Using this strain, we investigated whether the identified genetic evolution of NDV is accompanied by antigenic evolution. In this study we show that a live vaccine that is antigenically adapted to match the genotype VII NL/93 outbreak strain does not provide increased protection compared to a classic genotype II live vaccine. When challenged with the NL/93 strain, chickens vaccinated with a classic vaccine were completely protected against clinical disease and mortality and virus shedding was significantly reduced, even with a supposedly suboptimal vaccine dose. These results suggest that it is not antigenic variation but rather poor flock immunity due to inadequate vaccination practices that may be responsible for outbreaks and spreading of virulent NDV field strains.     

Nicotinic acetylcholine receptor chimeras of rat α7 and Drosophila SAD reveal species-specific agonist binding regions

Species-specific agonist binding regions of nicotinic acetylcholine receptors (nAChR) were examined. Imidacloprid and physostigmine (Phy) selectively activated insect nAChR composed of Drosophila second alpha-like subunit (SAD) and chick β2, in contrast to rat α7 nAChR. The Phy-activated currents were α-bungarotoxin (α-BGT) sensitive, suggesting activation at the agonist binding loop C. Several SAD-α7 chimeras were constructed, by switching agonist binding regions, and expressed in oocytes. Though none of the chimeras was activated by a range of nicotinic agonists, [¹²⁵I]α-BGT binding revealed homomeric assembly of all chimeric cDNAs. Phy differentially displaced [¹²⁵I]α-BGT from the nAChR chimeras, suggesting that the β subunit is not involved in Phy binding, and that Phy targets the insect agonist binding loop C.     

Back-calculation method shows that within-flock transmission of highly pathogenic avian influenza (H7N7) virus in the Netherlands is not influenced by housing risk factors

To optimize control of an avian influenza outbreak knowledge of within-flock transmission is needed. This study used field data to estimate the transmission rate parameter (β) and the influence of risk factors on within-flock transmission of highly pathogenic avian influenza (HPAI) H7N7 virus in the 2003 epidemic in The Netherlands. The estimation is based on back-calculation of daily mortality data to fit a susceptible-infectious-dead format, and these data were analysed with a generalized linear model. This back-calculation method took into account the uncertainty of the length of the latent period, the survival of an infection by some birds and the influence of farm characteristics. After analysing the fit of the different databases created by back-calculation, it could be concluded that an absence of the latency period provided the best fit. The transmission rate parameter (β) from these field data was estimated at 4.50 per infectious chicken per day (95% CI: 2.68–7.57), which was lower than what was reported from experimental data. In contrast to general belief, none of the studied risk factors (housing system, flock size, species, age of the birds in weeks and date of depopulation) had significant influence on the estimated β.     

Genetic data from avian influenza and avian paramyxoviruses generated by the European network of excellence (EPIZONE) between 2006 and 2011--review and recommendations for surveillance

Since 2006, the members of the molecular epidemiological working group of the European "EPIZONE" network of excellence have been generating sequence data on avian influenza and avian paramyxoviruses from both European and African sources in an attempt to more fully understand the circulation and impact of these viruses. This review presents a timely update on the epidemiological situation of these viruses based on sequence data generated during the lifetime of this project in addition to data produced by other groups during the same period. Based on this information and putting it all into a European context, recommendations for continued surveillance of these important viruses within Europe are presented.     

Effect of milk and brewing method on black tea catechin bioaccessibility

The aim of this study was to investigate whether milk reduces the bioaccessibility of tea catechins, which would compromise tea beneficial effects ascribed to polyphenols. Adding milk to black tea has been shown to lead to polyphenol-protein complexes. So far, data on the intestinal stability of polyphenol-protein complexes are scarce. English black tea (0.93 ± 0.06 mol/L total catechins) and Indian black tea (1.83 ± 0.08 mol/L catechins) were prepared with skimmed or full-fat milk and subjected to simulated gastric, small intestinal, and brush border digestion. Adding milk (5.6-40%) to tea results in a decrease of total catechin (TCAT) recovery. However, the bioaccessibilities of TCAT of tea with milk versus tea controls were comparable (p > 0.05). The type of milk did not influence TCAT recovery during all digestive stages (p > 0.05). Polyphenol-protein complexes are degraded during digestion. It is very unlikely that consumption of tea with or without milk will result in differences in catechin plasma concentration.     

H5N1 Virus Attachment to Lower Respiratory Tract

Highly pathogenic avian influenza virus (H5N1) may cause severe lower respiratory tract (LRT) disease in humans. However, the LRT cells to which the virus attaches are unknown for both humans and other mammals. We show here that H5N1 virus attached predominantly to type II pneumocytes, alveolar macrophages, and nonciliated bronchiolar cells in the human LRT, and this pattern was most closely mirrored in cat and ferret tissues. These findings may explain, at least in part, the localization and severity of H5N1 viral pneumonia in humans. They also identify the cat and the ferret as suitable experimental animals based on this criterion.