Distinct transcriptional profiles of HIV- and CMV-specific CD8 T cells in HIV progressors and long-term non-progressors

Abstract Antiretroviral treatment of HIV infected individuals cannot eliminate the HIV reservoir and immune control of HIV is rarely seen upon treatment interruption. In long-term non-progressors (LTNP), an effective CD8 T cell response is thought to contribute to be immune control of HIV. Here we studied the transcriptional profile of virus specific CD8 T cells to gain molecular insights in CD8 T cell functionality in HIV progressors and LTNP. Principal component analysis revealed distinct overall transcriptional profiles between the groups. The transcription profile of HIV-specific CD8 T cells of LTNP groups was associated with increased protein/RNA metabolism pathways, indicating an increased CD8 T cell functionality. In contrast, CMV-specific CD8 T cells from progressors showed increased expression of genes related to effector functions and suggests recent antigen exposure. Our data shows that changes in the energy demanding RNA and protein metabolism may drive dysfunctionality of HIV-specific T cells changes during chronic HIV infection.