12 November 2008

Telomeres and HIV infection

Alexey Levin, Voice of AmericaEmployees of the AIDS Institute at the University of California at Los Angeles and the biotechnology company Geron Corporation in a series of experiments have discovered another opportunity to suppress the reproduction of the immunodeficiency virus.



So far, it has been implemented only on laboratory cultures of human immune cells, but scientists do not see any fundamental obstacles to the use of this therapeutic technique in practical medicine. An article by Rita Effros and co-authors, which will be published by the Journal of Immunology on November 15, is devoted to this work.

As you know, the AIDS virus is extremely harmful. It directly affects a certain family of immune cells, the so-called helper lymphocytes (literally, helpers). These lymphocytes by themselves can neither kill cells that have already undergone a viral attack, nor produce specialized proteins-antibodies that are able to block viral particles in the blood plasma.

However, helper lymphocytes recognize the pathogen that has penetrated into the human body and, with the help of chemical signals, cause a multi-stage immune response. It leads to increased production of protective antibodies, as well as to rapid maturation and reproduction of killer lymphocytes, which begin to destroy cells infected with the aggressor virus.

The immunodeficiency virus causes mass death of helper lymphocytes and thereby makes the immune system unable to produce antibodies or to form killer cells.

However, the meanness of the virus is not limited to this. Now there are complexes of antiviral drugs that suppress its reproduction very well. However, deeply hidden viruses still remain in the tissues of infected people, which remain viable and can be activated many years after the start of drug therapy. Here lies one of the main reasons why a complete cure from HIV infection is not yet possible.

This constant presence of the virus in an infected body causes dangerous overload of the immune system. Killer lymphocytes out on the hunt are forced to constantly multiply, but this process has its limits. As you know, the DNA contained in the cell nuclei, which nature uses to record genetic information, is packed into separate blocks, chromosomes (humans have 23 of them).

At the ends of the chromosomes there are special areas, telomeres. They do not encode any information about the structure of proteins, but they protect the ends of chromosomes from sticking together, and also prevents the loss of information during cell division.

However, with each such division, the telomeres are shortened somewhat. When their length falls below the permissible limits, the cell loses the ability to divide. For this reason, most cells age and die by a certain age.

But this rule has its exceptions. Each telomere consists of many repeats of a chain of six nucleotides, which is exactly the same in all animals from the simplest unicellular to humans (in plants it is one nucleotide longer).

Since time immemorial, nature has invented the enzyme telomerase, which can attach such chains to telomeres and thereby prevent them from being excessively shortened. It works very actively during the development of the embryo, but then ceases to be synthesized in most cells, with the exception of those that are supposed by nature to retain the ability to multiple divisions (these are primarily eggs and spermatozoa, as well as stem cells).

Telomerase is also activated in the cells of malignant tumors, which is why they can grow without restrictions.

Telomerase genes also work in killer lymphocytes, which also have to multiply rapidly to perform their tasks. However, the hunt for hidden immunodeficiency viruses turns out to be so long that these genes gradually stop turning on.

In principle, lymphocytes can be kept in combat condition for longer by introducing additional genes of this type into them. Such operations are successful on laboratory cultures, but as a means against AIDS, of course, they are not suitable.

However, telomerase can also be helped by chemical exposure. In this case, this is exactly what Professor Effros and her colleagues did. They resorted to the help of the substance TAT2, isolated from the cells of the root of Astragalus membranum, a plant from the legume family.

It has long been used in Chinese medicine as a restorative, choleretic and diuretic and medicine for normalizing blood pressure. Not so long ago, it was proved that its component TAT2 spurs telomerase activity in some cells.

This information was used by scientists from Los Angeles. To begin with, they tested and confirmed that TAT2 prevents telomere shortening in killer lymphocytes isolated from the blood of both healthy people and, in particular, AIDS patients.

During these experiments, it also turned out that TAT2 causes killer cells to synthesize gamma interferon and several other biologically active substances that slow down the reproduction of the immunodeficiency virus.

Then the experimenters again produced a culture of stimulated killer lymphocytes and combined it with a culture of helper lymphocytes, also borrowed from the blood of HIV carriers. In such an environment, helpers have become much worse at producing new viral particles.

The authors of the article in the Journal of Immunology believe that the discovered effect deserves careful study. Who knows, maybe on the basis of TAT2 it will actually be possible to create not only new drugs for HIV infection, but also remedies for other viral infections.

Or, perhaps, this task will be performed not by TAT2, but by some more powerful telomerase activators that have yet to be discovered or created. As they say, the future will show.

Portal "Eternal youth" www.vechnayamolodost.ru12.11.2008

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