Proteins on T cells act as entry ports for the HI virus
Despite many years of intensive research, no cures for HIV have yet been developed. If the HI virus gets into a person's blood, it attacks his immune system and paralyzes the body's own defenses. In order to penetrate the body cells, the HI virus receives help from proteins that sit on the surface of the so-called T lymphocytes (T cells), the helper cells. Chinese researchers have now succeeded in deciphering the structure of one of the proteins, CCR5. The findings could be used in the future to develop drugs that reliably block CCR5. A cure for AIDS would not have been found with this either.
HIV arrives in T cells with the help of certain proteins The human immunodeficiency virus (HIV) is one of the most feared viruses worldwide. If left untreated, it usually leads to an outbreak of AIDS after an incubation period of several years (acquired immunodeficiency syndrome, translated: acquired immunodeficiency syndrome). The HI virus attacks the immune system by attacking the T cells, which subsequently die. In this way, the body's own defense is destroyed, so that it becomes powerless against other, actually harmless viruses and bacteria in the course of the infection.
As early as the 1990s, scientists discovered the mechanism by which the HI virus penetrates the body's cells. Proteins (proteins) like CCR5 sit on the surfaces of the T cells and act as entry ports for HI viruses similar to the key-lock principle. There are now HIV medications that block this mechanism of action. This includes Maraviroc. The agent prevents the HI virus from docking on the surface of CCR5. However, since there is not just one form of CCR5 but many different types, the drug is ineffective whenever CCR5 types are located on T cells that have a low affinity for maraviroc. A means should therefore be found that can reliably block all types of the protein. But that is precisely the difficulty, especially since until recently the exact inhibitory mechanism for the protein was not known.
HI virus can change its shape Recently, Chinese scientists led by Beili Wu from the Chinese Academy of Sciences solved this riddle by taking the first high-resolution images of the complex from CCR5 and Maraviroc. Their results were published in the science magazine. In their investigations, it was found that the drug does not block the entry of the HIV receptor, but rather “attaches” from behind to CRR5 and thus changes the shape of the protein. Another important finding of the researchers is that the images allow statements about which types of CCR5 cannot be blocked by Maraviroc. Their dome-shaped, twisted shape prevents the medication from accumulating. "This knowledge could help us to optimize drugs such as Maraviroc and to develop a new generation of drugs," quotes "Zeit-Online" scientist Wu.
But even if it were possible to develop an HIV drug that blocks all types of CCR5, further means would have to be found to inhibit the other proteins that the HI virus uses as an entry gate into the cells. One of these proteins is CXCR4. If the HI virus can no longer get into the T cells via CRR5, it changes its shape so that it can attach to CXCR4.
Wu successfully deciphered the CXCR4 structure six years ago. A comparison of the two proteins showed that their structure is similar. Only small deviations are responsible for the fact that they are preferred by different HIV variants, said Wu. "With these findings, drugs could soon be developed that block both CXCR4 and CCR5," the newspaper quotes the scientist. (Ag)