User:Siesel.12/sandbox

Final Edits I Made to the Wikipedia Page
https://en.wikipedia.org/wiki/Evolution_of_influenza

Reassortment occurs in similar fashion as chromosome crossover events, as two different viral strains may come in contact and transfer some of their genetic information. This crossing-over event creates a mixture of the two viral strains, which may replicate as one hybrid virus that expresses traits from both original viruses.

The mechanism of the evolutionary force of antigenic shift allows influenza viruses to exchange genes with strains that infect different species. Under this mechanism, a human influenza virus could exchange genes with an avian strain, and that is how pandemic strains arise. There have been three occurrences of pandemics caused by antigenic shift since 1900, and it could just as easily happen again. The cause of the antigenic drift lies in the mechanisms of RNA synthesis itself. Mutations arise very easily simply due to the error prone RNA polymerase and its lack of proofreading mechanisms. These mutations lead to subtle changes in the HA and NA genes which completely changes the infectious capabilities of the virus. These changes allow for almost endless possibilities for new viral strains to arise

By looking at how previous strains have evolved and gained new traits, the information can be applied to predict how current strains can evolve and even how novel strains might come about. Another use of phylogeny for predicting future viral dangers would be through using phylogeography. By studying how past strains have evolved while spreading to different geographic regions can allow scientists to predict how a strain might accumulate new mutations through its geographic distribution and the information could be used to protect different populations.

All of these methods using historical data can help to diminish the effects of new influenza virus strains each flu season. By attempting to predict future mutations in HA and NA genes, scientists can choose vaccination strains that are likely to match future viruses, so antibodies can quickly recognize and mount an immune response against the virus. The one setback in this approach is that it is not useful against strains that evolve through antigenic shift (reassortment). It is impossible to predict when and with which strains these events will occur, and the fact that it could happen with strains from different species makes it all the more difficult a method is found to accurately predict what mutations will arise and when they come about, vaccines will continue to be created purely on guesswork with no guarantee that they will provide total protection from influenza.

Siesel.12 (talk) 03:30, 14 November 2014 (UTC)

FINAL DRAFT OF PAPER
The influenza virus is immensely impactful and infects around 5-15% of the world’s population each year, around 1.1 billion people (Westgeest et al. 2014). In 1918, a pandemic of Spanish Influenza caused the death of over 40 million people around the world (Clancy 2008). The morbidity and mortality caused by this virus is tremendous and due to evolutionary tools, there are many hurdles in the way of being able to stop it. The influenza virus, consisting of eight single stranded RNA molecules, takes advantage of mechanisms of evolution to adapt and increase its fitness over the years so as to increase its ability to infect hosts (Xu et al. 2014).

The influenza genome consisting of eight, negative-sense, single-stranded RNA’s causes the hospitalization of over 100,000 people each year in the United States (Clancy 2008). Preventative measures have been developed and are in place, such as vaccinations and personal hygiene education programs, but they do not come close to fully combating the problems associated with the viruses. Vaccinations do have very positive impacts on abating the morbidity and mortality associated with influenza, but each year scientists have to purely make predictions about which strains of the virus will be a problem, using historical data and educated guesswork, with no guarantee that there will be a big impact. The challenging task of predicting which strains to vaccinate against is necessary due to the modes of evolution that the viruses utilize.

The main mode of evolution for the influenza virus is antigenic drift (Clancy 2008). Antigenic drift is caused by mutations in antibody-binding sites that accumulate over time. These mutations allow for vaccinated people to be infected with a different virus, as their antibodies cannot detect it due to the differing binding sites from the vaccine. There are two major genes controlling these sites, the HA and NA genes, producing the proteins haemagglutinin and neuraminidase, respectively (Xu et al. 2014). There is high genetic variability between different strains of the influenza virus for these genes, which is why different vaccines are produced each year. The cause of this antigenic drift, the variability of the antibody binding genes, lies in the mechanism of RNA transcription.

RNA polymerase is not a very precise enzyme. Errors are seen quite often and RNA polymerase does not contain proofreading mechanisms. These points are the cause for the drift in the genes. Mutations in the HA and NA genes can be quite subtle, but have the potential to allow the virus to evade the innate and adaptive immune responses of the host for some time. The act of evading the immune system response causes selection to occur for those viral strains with the newly mutated HA and NA genes, as the other strains will be destroyed by immune cells. It is the selection for these influenza strains that will ultimately lead to the decline of the virus, as once it infects enough people, attention is brought to it and a vaccine is produced. That is not to say that the virus loses the evolutionary race, as new mutated strains are formed constantly and are infecting humans and other organisms. One would think that harmful mutations could arise in a viral strain of influenza, which would lead to its extinction, but there is another mechanism of evolution and genetics that helps prevent that from occurring (Peng et al. 2014).

Genetic reassortment provides a means for the harmful genes to exist within a gene pool without expressing its harmful effects. This allows the viral strains to hold on to gene sequences in a gene pool that are not expressed, but which might resurface at a later time. This occurs due to the mechanism of genetic reassortment. This phenomenon happens just like chromosomes in dividing cells crossing over and exchanging genetic information, but in the influenza virus, this can occur between two different viral strains and can lead to serious problems for health. When a human or animal is infected with two different influenza viruses, they can exchange some of the RNA gene segments and replicate as one hybrid virus (Peng et al. 2014). This allows for the progeny virus to present characteristics from both of the parent strains. This is a very important mechanism for influenza viruses to utilize to gain different strengths and traits. There is another evolutionary force that exists that leads to very lethal strains of influenza, and it shares a similar name to antigenic drift.

Antigenic drift is always occurring in the viruses, but another force, antigenic shift, occurs less often but carries a greater impact. Antigenic shift occurs when there is a drastic change in the genes of the virus. This most often occurs in the HA gene and affects the antibody binding, but antigenic shift can also occur in other ways (Shi et al. 2010). Most of the strains of influenza that cause pandemics arise due to antigenic shift. Genes from human influenza and genes from other animal influenza viruses, such as avian, equine, or swine, combine and infect humans. These events are highly unpredictable and people usually have no protection from the viruses produced, which is why these strains usually gain pandemic statuses. There have been three occurrences of pandemics caused by antigenic shift since 1900, and there is little that can be done to prevent it from happening again as there is no way to pinpoint when or how it will happen next (Clancy 2008). While there is little that can be done in preventing influenza viruses from infecting humans at this time, there are ways in which the fitness and rate of mutation of certain strains can be used to predict possible strains to vaccinate against.

With the use of modern technology, humans are starting to fight back against influenza by trying to stay a step ahead of it by looking at the virus’s past and predicting its future. This can be done in many different ways but none offer a guarantee of what the next virus is that will cause an epidemic or pandemic. By looking at the past fitness of strains by looking at haemagglutinin, researchers can predict which mutations in the HA gene can increase an influenza virus’s fitness. Through seeing and understanding which mutations or sequences of the gene confer the greatest protection against host antibody binding, scientists can see where selection would take a certain influenza strain in the future. This technique allows vaccines to be produced for HA proteins that selection should cause to be involved in new influenza viruses, which can preemptively protect people against a virus that is not yet existent (Luksza and Lassig 2014). Another technique is to study other influenza-like illnesses and how they are spread. Historical data can be used that matches the current environment of influenza outbreaks and can give very important insight into how the virus might be transmitted from person-to-person and from one geographic area to another. This information can bring to light possible ways in which the virus can move through hosts and across areas and gain different traits and genetic variance. This is analogous to an animal migrating to a new area and introducing new genes or traits into a gene pool. The movement of the influenza virus can be predicted which allows researchers to predict which other strains the virus could come in contact with and which organisms or viruses it could experience antigenic drift or antigenic shift with (Viboud et al. 2003). These two methods have the potential to prevent future epidemics and pandemics by utilizing influenza data and historical outbreaks of disease and illness.

One of the most important tools in analyzing the evolution of influenza viruses is comparison of current strains to past strains to determine the evolutionary phylogeny. Understanding the long term evolution of influenza can lead to predictions about future changes within the genome and will allow for better protection from illness. The human influenza virus was first isolated in 1918, and has been evolving ever since then. This has led to countless HA and NA types, which are seen in the influenza naming such as the H1N1 and H3N2 influenza. An analysis of all isolated subtypes of the human influenza viruses from the period of 1918-2009 has shown that one gene, NS (nonstructural), has been circulating in the same form since the 1918 pandemic (Xu et al. 2014). This information shows how some genes may be kept in the genome over long periods of time as they either increase fitness or are somehow connected to other genes that increase the virus’s fitness. Other studies have shown how screenings during influenza outbreaks can highlight the path the virus takes in spreading from place-to-place. Studying immunoglobulin G (IgG) levels during infections can show whether the virus is present or not, and by collecting enough data from populations in different areas, a viruses path of transmission can be determined. Finding out the path can give information in the virulence of the virus and how easily it may be transmitted due to genetic traits. Knowing this shows which other strains the virus in question can come in contact with and undergo antigenic shift, and can allow preventative measures to be put in place as a precaution for possible new influenza infections (Bruin et al. 2014).

All of the knowledge about the evolution of influenza has the potential to change the world. Influenza is one of the largest causes of illness in the world and causes countless deaths and hospitalizations around the world each year. The evolutionary forces at work in the viruses cause them to be in constant change to increase their fitness and adapt to changing environments. It is this sole reason for the lack of one single vaccine to prevent all influenza. It is also this one fact that drives the research into the history and evolution of the influenza viruses, as understanding the mechanisms of change they utilize could lead to a cure-all vaccination that would stop influenza infections once and for all.

References: Bruin, E.de, J.G. Loeber, A. Meijer, G.Martinez Castillo, M.L.Granados Cepeda, M.Rosario Torres-Sepúlveda, G.J.C. Borrajo, et al. 2014. "Evolution of an influenza pandemic in 13 countries from 5 continents monitored by protein microarray from neonatal screening bloodspots". Journal of Clinical Virology. (31).

Viboud C, Boelle PY, Carrat F, Valleron AJ, Flahault A. 2003. “Prediction of the spread of influenza epidemics by the method of analogues”. American Journal of Epidemiology 158(10):996–1006.

Clancy, S. 2008. “Genetics of the influenza virus”. Nature Education 1(1):83

Luksza M., and Lassig M. 2014. "A predictive fitness model for influenza".Nature. 507 (7490): 57-61.

Peng J, H Yang, H Jiang, YX Lin, CD Lu, YW Xu, and J Zeng. 2014. "The origin of novel avian influenza A (H7N9) and mutation dynamics for its human-to-human transmissible capacity". PloS One. 9 (3).

Shi, Weifeng, Fumin Lei, Chaodong Zhu, Fabian Sievers, Desmond G. Higgins, and Justin Brown. 2010. "A Complete Analysis of HA and NA Genes of Influenza A Viruses".PLoS ONE. 5 (12): e14454.

Westgeest KB, CA Russell, X Lin, MI Spronken, TM Bestebroer, J Bahl, van Beek R, et al. 2014. "Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011". Journal of Virology. 88 (5): 2844-57.

Xu, Jianpeng, Haizhen A. Zhong, Alex Madrahimov, Tomáš Helikar, and Guoqing Lu. 2014. "Molecular phylogeny and evolutionary dynamics of influenza A nonstructural (NS) gene". Infection, Genetics and Evolution. 22 (Suppl.): 192-200.

Siesel.12 (talk) 00:29, 14 November 2014 (UTC)

Evolution of Influenza
https://en.wikipedia.org/wiki/Evolution_of_influenza

What I Added to the Page
It is the antigenic drift of the HA and HN genes that allow for the virus to infect humans that receive vaccines for other strains of the virus.

Suggestions for Wikipedia Page
Possible Edits to the Page

1. The lead section of the article could be improved to include a little more information related to the evolution of the virus rather than discussing aspects of the virus itself.

2. The section "Mechanisms of Evolution" needs a little more scientific data to bolster the ideas. I would recommend adding how various strains have utilized the mechanisms to change from year-to-year.

3. More information could also be given for the analysis section as well. More examples could be given as to how strains are believed to or have been proven to have evolved from ancestral strains from different species and areas geographically.

Siesel.12 (talk) 00:13, 1 October 2014 (UTC)

Summaries of References
This article discusses the evolution of influenza strains from a common ancestor. It goes on to describe how the H7N7 equine subtype and the first avian subtype branched off of the common ancestor and how in 1872 and 1873, a severe influenza virus was seen in horses and later on was seen in birds, suggesting that these two subtypes branched off around this time. The rest of the article describes how the virus is spread around the globe.

This scientific article discusses how the human influenza virus H3N2 evolved over the years from 1968-2011. It discusses how antigenic drift as well as mutation and reassortment continued to evolve the virus over time. The nucleotide and amino acid substitutions are discussed and how they changed over the course of the study and what effects that has on the evolution of the virus.

This article focuses on a broad prediction system of random mutations over time to asses the possible evolution of the influenza strains from year-to-year. The ability for viruses to increase fitness via mutations is highlighted and then goes on to talk about how the mutations at epitopes can be predicted so as to produce more efficient vaccines.

The circulation of a strain of influenza was monitored for a year in this study. The authors discuss how the strain spread in the cycle of the pandemic and noted which countries were exposed at different times and the effect the virus had in the country.

This article talks about the H7N9 strain in China and how it evolved and became more efficient and virulent in its human-to-human transmission. The article discusses the HA and NA region differences and traces the virus back to where it was originally seen. The researchers then go on to discuss in how many years it would be probable for an avian strain to be able to infect humans.