GLUTORHIV · Glucose metabolism and mTOR pathway role in CD8+ T cell control of HIV-1
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-04-01 → 2018-03-31
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Glucose metabolism and mTOR pathway role in CD8+ T cell control of HIV-1
Antiretroviral therapy can decrease HIV-1 below the limit of detection but fails to eliminate the virus that remains in latent reservoirs. New strategies to better control the virus must be developed. The HIV-controllers (HIC) are a rare group of patients infected by HIV-1 who can control the virus below the limit of detection for years without antiretroviral therapy. Spontaneous control of HIV is generally associated with an enhanced capacity of CD8+ T cells to eliminate infected CD4+ T cells, but the molecular characteristics of these highly functional CD8+ T cells are largely unknown. Based on our preliminary data, We made the hypothesis that the extraordinary HIV suppressive capacity of HIV-controllers CD8+ T cells during chronic infection might be associated with an optimal modulation of mTOR pathway (important for differentiation and function) and glucose metabolism (regulates activation, differentiation and functions) fueling those cells.
Data: CORDIS, © European Union
Project objective
Antiretroviral therapy can decrease HIV-1 below the limit of detection but fails to eliminate the virus completely. One of the main goals of a HIV-1 vaccine is the generation of cytotoxic CD8 T cell responses that counteract the virus. CD8 T cells participate in the control of viremia early but progressively show weakened functions, which leads to loss of virus control. HIV controllers are a rare group of infected patients who can control the virus for years without antiretroviral therapy. CD8 T cells from HIV-controllers display an outstanding capacity to eliminate infected CD4 T cells ex vivo but the underlying mechanisms are still not understood.Preliminary data aiming at establishing a single cell transcriptional signature associated with control of HIV suggest an important role of the mTOR pathway during the chronic stage. This pathway plays a major role in glucose metabolism and CD8 T cells cytotoxic function. This raises the hypothesis that the extraordinary HIV-suppressive capacity of HIV-controllers CD8 T cells is associated with the modulation of mTOR pathway and glucose metabolism.This project aims to 1) Study the single cell gene expression of HIV-specific CD8 T cells in HIV patients longitudinally from acute to chronic stages and understand the factors linked to control and loss of function of CD8 T cells during disease progression. 2) To characterize the role of mTOR pathway in the ability of CD8 T cells from HIV-controller to eliminate infected cells and test if this pathway can be modulated to fine-tune anti-HIV CD8 T cells responses. 3) To understand if an optimal glucose metabolism is necessary for CD8 T-cells suppression of HIV and if this capacity can be improved by increasing available glucose. This work will help to understand the characteristics of effective CD8+ T cell responses against HIV and may guide the development of anti-HIV vaccines or immunotherapies to induce HIV controller-like responses in HIV-infected progressors.
Original text from CORDIS.
Participants
- INSTITUT PASTEUR · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union