Emerging Role and Characterization of Immunometabolism: Relevance to HIV Pathogenesis, Serious Non-AIDS Events, and a Cure

Abstract

Immune cells cycle between a resting and an activated state. Their metabolism is tightly linked to their activation status and, consequently, functions. Ag recognition induces T lymphocyte activation and proliferation and acquisition of effector functions that require and depend on cellular metabolic reprogramming. Likewise, recognition of pathogen-associated molecular patterns by monocytes and macrophages induces changes in cellular metabolism. As obligate intracellular parasites, viruses manipulate the metabolism of infected cells to meet their structural and functional requirements. For example, HIV-induced changes in immune cell metabolism and redox state are associated with CD4+ T cell depletion, immune activation, and inflammation. In this review, we highlight how HIV modifies immunometabolism with potential implications for cure research and pathogenesis of comorbidities observed in HIV-infected patients, including those with virologic suppression. In addition, we highlight recently described key methods that can be applied to study the metabolic dysregulation of immune cells in disease states.

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

“…Metabolic dysfunction of immune cells in HIV-positive individuals is emerging as a hallmark of HIV infection, with important implications in disease pathogenesis and progression [ 1 – 4 ]. It is now recognized that glucose transporter 1 (Glut1), the major transporter of glucose on immune cells, is selectively essential for CD4+ T cell activation and effector function [ 5 ].…”

CD4 T Cell Metabolism Is a Major Contributor of HIV Infectivity and Reservoir Persistence

“…These along with continued virus production particularly in lymphoid tissue despite ART [1], represent the key sources of viral rebound following cessation of ART. An increasing body of work has brought the role of immunometabolism in HIV pathogenesis into focus, together highlighting an intricate link between glucose metabolic disorder, activation status, and HIV permissivity in CD4 T cells [2][3][4]. These studies have expanded our understanding of immune activation and HIV replication and persistence considerably [5][6][7][8].…”

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

“…The metabolism of monocytes and T lymphocytes can change dramatically upon activation, with both activated cell types upregulating surface expression of glucose transporter-1 (GLUT1) for efficient function [5–8]. The percentage of GLUT1-expressing monocytes and CD4 T lymphocytes is elevated in both untreated and cART-treated PLWH when compared to uninfected persons [5,6].…”