Emergence and Fixing of Antiviral Resistance in Influenza A Via Recombination and Hitch Hiking

The dramatic rise of oseltamivir resistance in the H1N1 serotype in the 2007/2008 season and the fixing of H274Y in the 2008/2009 season has raised concerns regarding individuals at risk for seasonal influenza, as well as development of similar resistance in the H5N1 serotype. Previously, oseltamivir resistance produced changes in H1N1 and H3N2 at multiple positions in treated patients. In contrast, the recently reported resistance involved patients who had not recently taken oseltamivir. Moreover, the resistance was limited to the H1N1 which had acquired H274Y. Using phylogenetic analysis I show that the fixing of H274Y was due to hitch hiking on a genetic background that acquired key changes from another circulating sub-clade. H274Y jumped from clade 2C (Hong Kong/2562/2006-like) to clade 1 (New Caledonia/20/1999-like) to clade 2B (Brisbane/59/2007-like) which included multiple introductions. Sub-clades that had acquired key changes on the neuramindase and hemagglutinin genes expanded and fixed of H274Y on H1N1. These changes led to the spread of adamantane resistance on clade 2C outside of Asia, followed by the spread of oseltamivir resistance in 2007/2008 and the fixing of H274Y in 2008/2009. The hemagglutinin change, A193T, was a key component and the coincident polymorphism, S193F, was linked to the fixing of adamantane resistance in H3N2. The aggregation of key polymorphisms onto different genetic backgrounds supports a mechanism of homologous recombination between co-circulating influenza sub-clades, and provides a rationale for the prediction of vaccine targets and emergence of antiviral resistance

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany

Complete genome sequences of two feline Leukemia virus subgroup B isolates with novel recombination sites

It is generally accepted that all primary isolates of feline leukemia virus (FeLV) contain a subgroup A virus (FeLV-A) that is essential for transmission. In contrast, FeLV-B is thought to arise de novo in the infected animal through RNA recombination events with endogenous FeLV transcripts, presumably through copackaging of RNA from endogenous FeLV and exogenous FeLV-A. Here, we report the complete genome sequences of two novel strains of FeLV-B (FeLV-2518 and FeLV-4314) that were isolated in the absence of FeLV-A. The env genes of these isolates have been characterized previously, and the 3′ recombination sites have been identified. We describe herein the 5′ recombination breakpoints of each virus. These breakpoints were found to be within the signal peptide of the env gene and the reverse transcriptase-coding region, respectively. This is the first report of a recombination site within the pol gene of an FeLV-B genome and the first genetic characterization of multiple independently arising FeLV-B isolates that have been identified without a functional FeLV-A ancestral virus

H5N1 Clade 2.2 Polymorphism Tracing Identifies Influenza Recombination and Potential Vaccine Targets

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 2. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 3.4. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 5. We traced polymorphism acquisition in Clade 2.2 sequences. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, Clade 2.2 sub-clades in Egypt, Russia and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by Clade 2.2 isolates in Egypt, Nigeria and Germany including aggregation of regional polymorphisms from each of these areas into a single Nigerian human hemagglutinin gene

Considering the User in the Wireless World

The near future promises significant advances in communication capabilities, but one of the keys to success is the capability understanding of the people with regards to its value and usage. In considering the role of the user in the wireless world of the future, the Human Perspective Working Group (WG1) of the Wireless World Research Forum has gathered input and developed positions in four important areas: methods, processes, and best practices for user-centered research and design; reference frameworks for modeling user needs within the context of wireless systems; user scenario creation and analysis; and user interaction technologies. This article provides an overview of WG1's work in these areas that are critical to ensuring that the future wireless world meets and exceeds the expectations of people in the coming decades

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, Kuwait, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. The recombination role is further supported by the high fidelity replication in swine influenza 9 and aggregation of single nucleotide polymorphisms in H5N1 clade 2.2 hemagglutinin 10

Impact of salt crystal size on in-mouth delivery of sodium and saltiness perception from snack foods

Fried, sliced potato crisps were flavored with sodium chloride of varying size fractions to investigate the impact of salt crystal size on the delivery rate of sodium to the tongue and resultant saltiness, measured over 65 s with a defined chew protocol (three chews, then holding the bolus in the mouth without swallowing). Salt crystal size impacted upon the delivery rate and perceived saltiness. The smallest crystal size fraction dissolved and diffused throughout the mouth to the tongue saliva faster than the medium and the largest ones; the smallest crystal size fraction also had the highest maximum concentration and greatest total sodium. These results correlated well with the sensory perceived saltiness, where the smallest crystal size fraction resulted in the fastest Tmax, highest maximum saltiness intensity and maximum total saltiness. The different delivery rates can be explained by differential dissolution kinetics and enhanced mass transfer of sodium across the saliva

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany