Evolution of influenza

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The virus causing influenza is one of the best known pathogens found in various species. In particular, the virus is found in birds as well as mammals including horses, pigs, and humans.[1] The phylogeny, or the evolutionary history of a particular species, is an important component when analyzing the evolution of influenza. Phylogenetic trees are graphical models of the relationships between various species. They can be used to trace the virus back to particular species and show how organisms that look so different may be so closely related.[1]

Mechanisms of evolution

Two common mechanisms by which viruses evolve are reassortment and genetic drift.[2]

Reassortment

Reassortment, also known as antigenic shift, allows new viruses to evolve under both natural conditions and in artificial cultures.[2] 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.[3] 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.[4] In fact, the 1957 evolution of the H2N2 virus is thought to be a result of reassortment.[2] In this case, human H1N1 strains and avian influenza A genes were mixed.[2] Infecting tissue cultures can demonstrate how pathogenic qualities can evolve for a particular species even though the reassorted virus may be nonpathogenic for another species.[2] A prime example of evolution under natural conditions is the reassortment of two avian influenza strains that were discovered in dead seals back in 1979.[2]

Drift

New viruses can also emerge by drift. Drift can refer to genetic drift or antigenic drift.[2] Mutation and selection for the most advantageous variation of the virus takes place during this form of evolution.[2] Antigenic mutants can evolve quickly due to the high mutation rate in viruses. 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[3] and it is the antigenic drift of the HA and NA genes that allow for the virus to infect humans that receive vaccines for other strains of the virus.[5] This evolution occurs under the pressure of antibodies or immune system responses.[2]

Transmission

Species and barriers

The transmission, or how the influenza virus is passed from one species to another, varies. There are barriers that prevent the flow of the virus between some species ranging from high to low transmission. For example, there is no direct pathway between humans and birds.[2] Pigs however, serve as an open pathway. There is a limited barrier for them to spread the virus.[2] Therefore, pigs act as a donator of the virus relatively easily.

Geographic differences

Phylogenetic maps are a graphical representation of the geographic relationships among species. They indicate that the human influenza virus is minimally impacted by geographic differences.[1] However, both swine and avian influenza does appear to be geographically dependent.[1] All three groups (avian, swine, and human) show chronological differences. The human influenza virus is retained in humans only, meaning it does not spread to other species.[1] Some lineages and sublineages of the virus emerge and may be more prevalent in certain locations. For instance, many human influenza outbreaks begin in Southeast Asia.[2]

Phylogenetic analysis

Phylogenetic analysis can help determine past viruses and their patterns as well as determining a common ancestor of the virus. Past studies reveal that an avian virus spread to pigs and then to humans approximately 100 years ago.[2] This resulted in human lineages further evolving and becoming more prominent and stable.[2]

Analysis can also feature relationships between species. The 1918 Spanish influenza virus demonstrates this. The hemagglutinin (HA) gene of the 1918 pandemic virus was closer in sequence to avian strains than other mammalian ones. Despite this genetic similarity, it is obviously a mammalian virus.[6] The gene may have been adapting in humans even prior to 1918.[6] Breaking down the phylogenetic history of the influenza virus shows that there is a common ancestor that reaches back before the 1918 outbreak that links the current human virus to the swine virus.[7] The ancestor was derived from an avian host.[2]

Future impact and prediction strategies

Phylogenetics

Looking at the past phylogenetic relationships of the influenza virus can help lead to information regarding treatment, resistance, vaccine strain selection, and of future possible influenza strains. 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.[8] Another use of phylogeny for predicting future viral dangers would be through using phylogeography. Various lineages may continue their presence and reassort indicating the importance of a complete-genome approach to determine new influenza strains and future epidemics.[9][10] 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.[11]

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.[4] Until 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.

Antiviral Resistance

In current years, there has been a huge increase in the amount of resistance to certain drugs, including the antiviral compound adamantane.[12] In fact, its resistance has recently climbed from 2 percent to nearly 90 percent.[12] These records of built up resistance infer that drugs, such as adamantine, will not be useful against the influenza virus in the future.

References

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