21 March 2008

"Jumping genes" of monkeys suggested a new way to treat HIV infection

An international team of scientists led by Professor Greg Towers of University College London has identified a combination of genes that prevent infection of monkeys with retroviruses. This discovery is extremely important, because the currently incurable HIV belongs to the retrovirus family.

According to the generally accepted theory, HIV, which entered the human population at the beginning of the 20th century, originated from SIV (monkey immunodeficiency virus). In order to overcome the interspecific barrier, the virus needs to learn how to bypass the innate immunity of the body, provided by the functioning of a combination of genes and their protein products. One of these genes, called TRIM5, protects the body of many primate species from retroviruses, but its human version was powerless against HIV.

The authors found that Asian rhesus monkeys have a complex "antiviral arsenal" that protects them from retroviruses. A detailed study of the TRIM5 gene of this species showed that in some individuals it is combined with the gene encoding the cyclophilin protein into the so-called TRIMCyp complex.

According to the authors, cyclophilin effectively binds virus particles penetrating into the cell, and the resulting gene fusion complex TRIMCyp has the ability to both capture and destroy them.

Впервые защищающий от ретровирусов комплекс генов TRIMCyp выявили в геноме южноамериканских совиных обезьян – трехполосых дурукули (Aotus trivirgatus)For the first time, the TRIMCyp complex was identified in the genome of South American owl monkeys – three-striped durukuli (Aotus trivirgatus), but until now these cute nocturnal creatures were considered a unique phenomenon.

The results of the new work showed that this complex independently appeared in two unrelated species, which is a vivid example of convergent (parallel) evolution – the acquisition of two unrelated organisms of the same characteristics as a result of adaptation to the same conditions. It is also an indicator of the evolutionary pressure that viruses like HIV can exert.

Professor Towers claims that this discovery is a good example of how "jumping genes" (transposons) can change the genetic profile of an organism, creating new useful genes. In addition, it opens up a promising new perspective for the development of new HIV treatments/AIDS.

About 25% of Rhesus monkeys have both the TRIM5 gene and the TRIMCyp complex, which significantly increases their resistance to viruses.

The immunity of other individuals is provided by various variants of the TRIM5 gene, which provides them with protection from various combinations of viruses. Apparently, the evolution of the TRIM5 gene occurs in the direction of ensuring the resistance of each mammalian species to a certain spectrum of viruses.

The authors plan, by forcibly merging the TRIM5 and cyclophilin genes, to create a humanized version of the TRIMCyp complex, which with the help of gene therapy can be embedded in hematopoietic stem cells. The introduction of such modified cells to the patient will gradually lead to the replacement of the original immune cells with HIV-resistant lymphocytes.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily


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