Metabolic pathways as regulators of HIV infection

Abstract

Activation of the immune system only occurs when stimulated cells generate sufficient energy to support their growth and proliferation. Moreover, efficient HIV-1 infection requires that CD4(+) T cells meet the energy demands involved in completing the different steps of the virus life cycle. In this review, we highlight recent studies revealing the importance of nutrient fuels, nucleotide metabolism and the oxygen microenvironment in regulating HIV-1 infection, T-cell differentiation and the generation of HIV-1-specific immune responses. Glucose uptake via the Glut1 glucose transporter is required for efficient HIV-1 infection of CD4(+) lymphocytes. Other nutrients can also be used as sources of energy and their utilization conditions the differentiation of CD4(+) T cells to distinct effector fates. The conversion of ATP to adenosine inhibits HIV-specific effector cells and the hydrolysis of dNTPs by SAMHD1 restricts infection. Furthermore, oxygen concentration modulates metabolic status, thereby altering T-cell differentiation and potential to mediate a specific immune response. The availability and use of energy resources in fluctuating environments regulate T-cell function and susceptibility to HIV-1 infection. Identification of the targets coordinating the selected metabolic pathways will advance new strategic avenues for controlling HIV-1 disease progression.