HIV passes through proteins in body cells

Proteins on T cells act like inlet ports for the HI virus

13/09/2013

Despite many years of intensive research, so far no cure for HIV could be developed. If the HIV virus enters a person's blood, it attacks its immune system and paralyzes the body's own defense. 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 decoding the structure of one of the proteins, CCR5. The findings could be used in the future to develop drugs that reliably block CCR5. But a cure for AIDS would not have been found.

HIV enters the T cells with the help of certain proteins
Human Immunodeficiency Virus (HIV) is one of the most feared viruses worldwide. If left untreated, it usually leads to the onset of AIDS (acquired immunodeficiency syndrome) after several years of incubation. The HI virus attacks the immune system by attacking the T cells, which subsequently die. In this way, the body's defense is destroyed, so that it becomes powerless in the course of infection against other, actually safe viruses and bacteria.

Already in the 1990s, scientists discovered the mechanism by which the HI viruses penetrate into the body's cells. Proteins (inlays) such as CCR5 sit on the surfaces of T cells and act as ports of entry for HI viruses similar to the key-lock principle. There are now HIV drugs that block this mechanism of action. This includes Maraviroc. The agent prevents the HI virus from docking on the surface of CCR5. However, as there is not one single 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. It would therefore have to find a means that all types of protein can reliably block. But that's exactly the difficulty, especially since until recently, not even the exact inhibition mechanism for the protein was known.

HI virus can change its shape
This puzzle was recently raised by Chinese scientists around Beili Wu of the Chinese Academy of Sciences by making the first high-resolution images of the complex of CCR5 and Maraviroc. Their results were in the trade magazine „Science“ released. Their research revealed that the drug does not block the entrance of the HIV receptor, but rather „from behind“ docked to CRR5, thus altering the shape of the protein. Another important finding of the researchers is that the images allow statements about which CCR5 types can not be blocked by Maraviroc. Their dome-shaped, twisted shape thus prevents the drug from attaching. „This knowledge could help us to optimize medicines such as maraviroc and to develop a new generation of medicines, "quoted „Time Online“ Scientist Wu.

However, even if it were possible to develop an HIV drug that blocks all CCR5 types, it would need to find additional ways to inhibit the other proteins that use the HIV virus as an entry portal into the cells. One of these proteins is CXCR4. If the HI virus can no longer enter the T cells via CRR5, it will change shape so that it can attach to CXCR4.

Six years ago, Wu succeeded in deciphering the CXCR4 structure. A comparison of the two proteins showed that their structure is similar. Only small deviations are responsible for the fact that they would be preferred by different HIV variants, explained Wu. „These findings could soon be developed drugs that block both CXCR4 and CCR5, "the newspaper quoted the scientist.