The “science” of Influenza genetics is far from well-developed concerning predictions. The literature remains peppered with phrases like "Surprisingly", "Unexpected" and "Data not provided" in areas that other studies claim to have proven; the "science" foundation for genetic prediction is yet small. Most leading Influenza researchers are unwilling and unable to go on public record with vectors or potential paths of viral development. The “science” of Influenza and viral genetics is relatively young and though ground is being gained in the content arena, predictability using the current two pillars dogma is rarely undertaken because the protocols were built in an era that had only a low quantity of low quality data. New models of thinking and new protocols of investigation are required that incorporate the proofs demonstrated within the current reservoir of available data.
The recent high availability of PF11 sequences and clinical reports has given us data to understand where the virus is going, especially the much desired and appreciated sequences from South America shared by the Mailman School of Public Health at Columbia University. The sequences are from Argentina where the highest official death count in the world has caused healthcare rationing in all 77 hospitals in the socialized medicine system of Argentina. Many other countries in Latin America are refusing health services due to supply, personnel and infrastructure failures.
Genetic Acquisition Analysis
A managed campaign of political and laboratory messages in the media continues to state that no changes are found in Pandemic Influenza H1N1. The underlying genetics database, however, demonstrates many acquisitions and a consistent trend of fitness-inducing polymorphisms. As samples have been added each week around the world, a pattern has emerged.
The pattern indicates a persistent hyper-morphic state on the PF11 background at certain positions within particular species. Of certain note is the directional movement on the Hemagglutinin (variously termed HA and H1) and Neuraminidase (variously termed NA and N1) segments. Though all Influenza consistently recombines with existing genetic material from proximal non-self strains, PF11 has demonstrated a march toward human-fit acquisition that is remarkable in speed and geographic spread.
The purpose of these point by point studies is to indicate and discuss several of those key polymorphisms and examine the potential next steps in humans. As you have seen finally released in the media, PF11 in the human-form has now been sequence-confirmed in birds and in swine, allowing hundreds of species as additional “mixing vessels” or recombination reservoirs. This predicted species jump, more importantly, provides flight-based transportation vectors that will easily number in the millions of infected birds with a potential pool of billions in various seasons.
Recall the CDC reports that 70% of all emerging diseases are zoonotic (originate in animals). The asymptomatic flight-based animals transport the disease from their land-based counterparts, the swine, who are playing their normal role as ideal mixing reservoirs for recombination due to their robust tolerance to many strains of Influenza. Pig=>Duck=>Human=>Chicken=>Pig and dozens of additional paired vectors of transmission have been confirmed between human, swine and avian species. The genetic transition state between species, the Influenza Flux, is dangerous for humans due to continual creation of novel antigen and species-specific phenotypical traits that strain the human immune system, elevate the potential for vaccine escape and may produce a negative interplay with that nemesis of vaccine scientists, Original Antigenic Sin (OAS).
OAS, in a few words, describes the physiological phenomenon observed since 1960 that antibody production to a novel virus is mediated and frequently downgraded by the priming epitope or first infection in an individual host from that species of virus (original childhood infection). Frequent exposure to novel antigens within a virus species (notably Influenza), via vaccine and/or natural infection, tends to create fewer and fewer new antibodies that bind properly to the slightly dissimilar recent virus / antigen. The documented process counter-intuitively invokes high-specificity memory B cells from the priming epitope (original childhood infection) which then feeds back signals to reduce the activation of naive B cells toward the new antigen. Studies observe situations where Antibody Secreting Cells (ASC) produce antibodies to earlier infections in a ratio higher than antibodies to the new infection.
In short, PF11 at this time continues to create a Hydra Effect, attacking the human with many different heads or genetic variations. The Hydra Effect coupled with the observed Interferon-Deranging Rapid Replication Viral (IDRRV) property creates a unique and daunting foe.
We will overview our findings on four gene segments with discussion on inter-segment correlations.
The pattern indicates a persistent hyper-morphic state on the PF11 background at certain positions within particular species. Of certain note is the directional movement on the Hemagglutinin (variously termed HA and H1) and Neuraminidase (variously termed NA and N1) segments. Though all Influenza consistently recombines with existing genetic material from proximal non-self strains, PF11 has demonstrated a march toward human-fit acquisition that is remarkable in speed and geographic spread.
The purpose of these point by point studies is to indicate and discuss several of those key polymorphisms and examine the potential next steps in humans. As you have seen finally released in the media, PF11 in the human-form has now been sequence-confirmed in birds and in swine, allowing hundreds of species as additional “mixing vessels” or recombination reservoirs. This predicted species jump, more importantly, provides flight-based transportation vectors that will easily number in the millions of infected birds with a potential pool of billions in various seasons.
Recall the CDC reports that 70% of all emerging diseases are zoonotic (originate in animals). The asymptomatic flight-based animals transport the disease from their land-based counterparts, the swine, who are playing their normal role as ideal mixing reservoirs for recombination due to their robust tolerance to many strains of Influenza. Pig=>Duck=>Human=>Chicken=>Pig and dozens of additional paired vectors of transmission have been confirmed between human, swine and avian species. The genetic transition state between species, the Influenza Flux, is dangerous for humans due to continual creation of novel antigen and species-specific phenotypical traits that strain the human immune system, elevate the potential for vaccine escape and may produce a negative interplay with that nemesis of vaccine scientists, Original Antigenic Sin (OAS).
OAS, in a few words, describes the physiological phenomenon observed since 1960 that antibody production to a novel virus is mediated and frequently downgraded by the priming epitope or first infection in an individual host from that species of virus (original childhood infection). Frequent exposure to novel antigens within a virus species (notably Influenza), via vaccine and/or natural infection, tends to create fewer and fewer new antibodies that bind properly to the slightly dissimilar recent virus / antigen. The documented process counter-intuitively invokes high-specificity memory B cells from the priming epitope (original childhood infection) which then feeds back signals to reduce the activation of naive B cells toward the new antigen. Studies observe situations where Antibody Secreting Cells (ASC) produce antibodies to earlier infections in a ratio higher than antibodies to the new infection.
In short, PF11 at this time continues to create a Hydra Effect, attacking the human with many different heads or genetic variations. The Hydra Effect coupled with the observed Interferon-Deranging Rapid Replication Viral (IDRRV) property creates a unique and daunting foe.
We will overview our findings on four gene segments with discussion on inter-segment correlations.
The reservoir of fitness-inducing polymorphisms available to PF11 is vast as we’ve determined 4 or more backgrounds in circulation that may have been slow, but consistent, donors to PF11.
The related reservoir has much more to offer in the coming months as the most important changes have either not yet been introduced or have not become fixed. Several of these candidate donor backgrounds are matches to provide one or more of the polymorphisms that have been demonstrated in the lab and shown clinically to strengthen Influenza against humans.
Remember that, although many are dying horrible deaths from PF11, this virus, as it stands today, is still most definitely hobbled / limited by many genetic shortcomings. The viral development process appears to be correcting those shortcomings by accepting consistent donations from the able reservoir of circulating Influenza strains worldwide.
We expect that PB2:627K (Increased Human Virulence) and NA:275Y (TamiFlu resistance) will be discovered widely in PF11. Relenza resistance is impossible to characterise at this time due to data paucity.
For a more complete and ongoing analysis, please read our PF11 Genetic Acquisitions studies.
For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.
