Allogeneic Immunity May Eliminate Latent HIV Reservoirs

Scientists have achieved a major breakthrough in the battle against HIV by uncovering the crucial role of allogeneic immunity in eliminating latent virus reservoirs. The discovery offers hope for the development of new strategies to cure HIV and improve the lives of millions of individuals living with the virus.

Previous research has shown that allogeneic hematopoietic stem cell transplantation (alloHSCT) from specific donors can cure HIV. However, the exact mechanism behind this therapy has remained elusive. To unravel this mystery, scientists conducted a study using a nonhuman primate model to investigate the virus clearance process following alloHSCT, focusing on the role of allogeneic immunity.

The study examined four patients who underwent alloHSCT from donors with a specific genetic mutation called C-C chemokine receptor 5 (CCR5Δ32/Δ32) and found that allogeneic immunity, particularly the graft-versus-reservoir (GVR) effects, plays a vital role in clearing the viral reservoir. The clearance process begins in the peripheral blood, then progresses to peripheral lymph nodes, and finally reaches the mesenteric lymph nodes connected to the gastrointestinal tract. This mechanism closely resembles the graft-versus-leukemia (GVL) effect observed in cancer treatment.

Over four years, the study closely monitored four nonhuman primate recipients of alloHSCT and observed an approx 1000-fold decrease in the simian immunodeficiency virus (SIV) reservoir in all recipients. Although the precise role of the CCR5Δ32/Δ32 donor immune system remains unclear, the research indicated that CCR5 deficiency provides early protection during engraftment. This protection prevents the infection of donor CD4+ T cells through cell-to-cell viral spread. In addition, the immune system of the donor that is engrafted into the recipient's body helps to fight off infections and remove any infected CD4+ T cells.

This breakthrough study will be critical to advancing the development of HIV cure strategies and validating their effectiveness in clinical settings.

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