艾滋病治愈者 z-bo 2020-09-16 400

　　"Berlin patient" Timothy Ray Brown is an American leukemia patient who also suffers from AIDS. In 2007, he came to Berlin to find Dr. Huth. At that time, Brown was in very bad condition and his condition was getting worse. It was almost here. On the verge of death. Then Huth made a decision: to perform a bone marrow transplant, first to treat leukemia. The result was unexpected. After 3 years of clinical observation, this transplant also cured Brown’s AIDS. The original bone marrow donors were not only very matched. It is consistent, and there is a mutated gene in the bone marrow that can naturally resist HIV. According to previous studies, this mutated gene is only present in a small number of northern Europeans.

　　Brown underwent bone marrow transplantation after irradiation. His bone marrow donors carried a genetic mutation that would make the CD4 cells lack the CCR5 receptor in the human body. The lack of the host would not be infected with HIV, and it would also cause the CD4 cells in their body. High resistance to HIV.

　　Several factors contribute to the treatment of HIV/AIDS patients: (1) The ablation of blood cells and immune cells after irradiation can kill all or many virus reservoir cells that have not been eliminated by antiretroviral therapy (ART); (2) CCR5 deletion mutations in donor cells can protect them and their offspring from HIV infection; (3) A "graft-versus-host" reaction occurs, where the transplanted cells and their offspring determine the host cells as foreign Source and aggressive, and eliminate HIV-positive reservoir cells that survived irradiation.

　　Guido Silvestri and colleagues from Emory University in the United States studied the effects of irradiation on the elimination of HIV-infected reservoir cells. Scientists use rhesus macaques (rhesus macaques) infected with simian immunodeficiency virus (SIV, a related species of HIV that can infect primates and cause diseases similar to AIDS) as an animal model. A total of 6 rhesus monkeys were used (3 of them served as controls and did not receive transplants). They transplanted hematopoietic stem cells into rhesus monkeys infected with chimeric monkey/human immunodeficiency virus (SHIV) for the first time and treated them with ART.

　　Before being infected with SIV, the researchers collected hematopoietic stem cells from 3 macaques. They also performed ART treatment on rhesus monkeys to reduce viral load and simulate the situation of human HIV-infected patients receiving ART treatment. Then, they exposed three macaques that had collected hematopoietic stem cells to high doses of radiation. This killed most of their existing blood cells and immune cells, including 94% to 99% of blood CDT4-T cells-the main target of HIV infection. After irradiation, transplant each macaque’s own detoxified hematopoietic stem cells. The latter can regenerate blood and immune cells and perform the same procedure on all three macaques within 3 to 6 weeks. Because the transplanted cells are not from different donors, graft-versus-host disease does not occur, nor is it observed.

　　After

　　, the scientists stopped ART treatment in 6 macaques. As expected, the virus rebounded rapidly in the control animals. Of the three transplanted animals, two also showed rapid rebound. The third rhesus monkey developed renal failure two weeks after stopping the ART treatment and was euthanized. At that time, there was still no detectable virus level in its blood, but post-mortem analysis showed that there were low levels of viral DNA in many tissues, and it was believed that none of the three macaques had been cured.

　　Researchers admit that the study has some limitations, including the small number of macaques and the short ART treatment time before irradiation and transplantation. However, they said, this study supports the hypothesis that "whole body irradiation of bone marrow can cause a significant decrease in virus reservoirs in blood cells, even if it is not enough to eliminate all reservoirs." These findings indicate that the use of CCR5 mutant donors and/or the presence of graft-versus-host disease plays a very important role in the cure of Berlin patients.

　　This proof-of-concept study shows for the first time that whole-body irradiation and hematopoietic stem cell transplantation are feasible in ART-treated SIV-infected rhesus monkeys. The researchers hope that further studies using this model will provide the treatment of human HIV infection. Key information.