The role of CD38 in HIV infection

Abstract

The widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression through different mechanisms. Therefore, investigating the role of CD38 in HIV infection and the potential signaling pathways that are involved may provide a new perspective on potential treatments for HIV infection. In the present review, the current understanding of the roles CD38 plays in HIV infection are summarized. In addition, the specific role of CD38 in the process of HIV infection of human CD4⁺ T lymphocytes is also discussed.

Keywords: ART; Abnormal immune activation; CD38 molecule; HIV.

Fig. 1

The activation of lymphocytes results in a vicious cycle. Persistent chronic overactivation of CD4⁺ T lymphocytes and CD8⁺ T lymphocytes after HIV infection, with significantly elevated levels of CD38 expression, which may predispose CD4⁺ T cells to HIV infection and further promote HIV replication, and as CD4⁺ T lymphocytes are depleted, the disease continues to progress, forming a cycle

Fig. 2

Enzymatic activity of CD38 molecules leads to internal alterations in CD4⁺ T cells. CD38 catalyzes the conversion of NAD to ADPR, cADPR, and NAADP, which reduces cytoplasmic NAD in CD4⁺ T cells, leading to a chronic Warburg effect that decreases mitochondrial function. The catalytic products of CD38 can activate calcium channels and increase cytoplasmic Ca²⁺ concentrations, further reducing mitochondrial integrity. Depletion of cytoplasmic NAD promotes the Warburg effect and continues to affect mitochondrial function and integrity. Elevated cytoplasmic Ca²⁺ concentrations further increase mitochondrial stress, which ultimately leads to decreased CD4⁺ T cell survival