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The clash of viruses and immune system

02 Jul

immune systemThe human genes in the history of “arms race” between viruses and the immune system. Anti-virus protection and virus proteins, being deceived, developed in the tracks. But the race in which the animals come out until the winners going on.

The arms race – an attribute not only human civilization. The confrontation of viral agents and the immune system of a living organism – an example of a far more inventive, much more ancient and infinite in its essence of the conflict.

Some historical details of the immune system to combat poxvirus is now known to scientists because of two scientific papers accepted for publication in Nature, and Nature Structural and Molecular Biology. A healthy body has a special mechanism to combat viruses, based on the protein kinase R, PKP (protein kinase R, PKR). When the double helix in the cell, this viral RNA is an important component of the immune system communicates with another protein – factor eIF2a, which in the normal state is used to initiate protein synthesis. However, in a bound state of eIF2a with PKR to perform its function is unable to. As a result, translation of all proteins is stopped and it stopped and the synthesis of new viruses. Viruses, in turn, is more than a million years trying to trick the immune prevail over the protection of protein kinase R by synthesizing cells in the body of the affected “forgery” under eIF2a – proteins KL3.

American Garmite Malik, a member of the Center for Research on Cancer the Fred Hutchinson in Seattle, and colleagues hypothesized that the evolutionary development of this kinase and the viral “fakes” are parallel.

So, in this opposition can try to track the stages of the escalation of wars of the protein when kinase evolved faster, and the stages of relative calm, accompanied by slow changes.

However, before you restore the history of the race, members of Malik was necessary to demonstrate that protein kinase R in the past, and indeed has been subject to evolutionary transformations associated with a positive natural selection. In the course of this selection in the population there is a large number of individuals with new benefits that make the whole more stable form of threats to the environment, including the virus.

Scientists have decoded the genes protein kinase R in 20 different primate species, the separation of the evolutionary branches are enveloped in a time interval of 30 million years. To separate the changes as a result of random mutations from those that were subject to natural selection, the researchers compared the rates of nucleotide substitutions of the two species – synonymous and nonsynonymous.

Assessing the relationship between the two types of mutations in the gene PKR in different species, scientists have been able to establish that positive natural selection in the evolution of this protein in more than present.

Most clearly manifested in this evolution martyshkovyh who underwent SIC code 22 nesinonimicheskie replacement without a single synonymous substitution!

In this comparison of the genetic lines of primates has shown that these changes were sporadic. In the course of evolution has been marked by the replacement of amino acids involved in binding the viral protein kinase, and K3L. According to the authors, it directly points to a periodic acceleration of the evolution of the immune system in response to the aggression of the virus evolved.

In its publication, scientists have noted that positive natural selection was detected in all three domains of PKR – fragment, responsible for communication with the double helix RNA spacer region and the kinase region. All of them correspond to the mechanisms linking viral agents with those parts of biological molecules. The most rapid evolution occurs in the P protein kinase domain, where there is direct contact with eIF2a. Perhaps, the evolution is going on under pressure from the counterfeits of viral translation factor.

Similarly, scientists have found evidence of positive natural selection and the structure of the viral “fake” protein K3L.

For example, in comparison with the K3L protein of variola virus and with the same protein of vaccinia virus, scientists have discovered an almost three times as many nonsynonymous mutations over synonymous. This suggests that poksvirusnye “forgery” under eIF2a is not reached in the past, the optimal configuration and these configurations were optimized for the destruction of healthy cells does not last long. Perhaps the evolution of protein K3L is following the change of protein kinase R.

However, Stefan Rothenburg from the laboratory of gene regulation and development at the Institute of Child Health and Human Development, the name of Eunice Kennedy Shriver in Maryland a different opinion. In a paper accepted for publication in Nature Structural & Molecular Biology, he and his colleagues showed signs of evolution of the vertebrate protein P under the pressure of poxvirus. Rothenburg team was able to demonstrate that a single amino acid substitution in the amino acid PKR mice, located in the same position in the human kinase makes rodents more resistant to the action of protein K3L. This mutation shows how the kinase, while maintaining its functionality, was not susceptible to the action of the viral agent.

The very same translation factor primates, protein eIF2a, in fact, have not changed at the level of its primary structure – the amino acid composition. In other words, protein kinase R evolves while remaining sensitive to its substrate, but not binding to the viral fakes like the K3L.

 
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Posted by on July 2, 2012 in civilization, Human

 

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