The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections

Abstract

CD39 is a marker of immune cells such as lymphocytes and monocytes. The CD39/CD73 pathway hydrolyzes ATP and adenosine, which has a potent immunosuppressive effect. CD39 regulates the function of a variety of immunologic cells through the purinergic signaling pathways. CD39+ T cells have been implicated in viral infections, including Human Immunodeficiency Virus (HIV), Cytomegalovirus (CMV), viral hepatitis, and Corona Virus Disease 2019 (COVID-19) infections. The expression of CD39 is an indicator of lymphocyte exhaustion, which develops during chronicity. During RNA viral infections, the CD39 marker can profile the populations of CD4+ T lymphocytes into two populations, T-effector lymphocytes, and T-regulatory lymphocytes, where CD39 is predominantly expressed on the T-regulatory cells. The level of CD39 in T lymphocytes can predict the disease progression, antiviral immune responses, and the response to antiviral drugs. Besides, the percentage of CD39 and CD73 in B lymphocytes and monocytes can affect the status of viral infections. In this review, we investigate the impact of CD39 and CD39-expressing cells on viral infections and how the frequency and percentage of CD39+ immunologic cells determine disease prognosis.

A Prospective Study Investigating Immune Checkpoint Molecule and CD39 Expression on Peripheral Blood Cells for the Prognostication of COVID-19 Severity and Mortality

“…In the present study, we investigated a reasonable number of ICPMs and also included CD39 as a marker for the purinergic signaling pathway. CD39 possesses ecto-(Ca +2 -MG +2 ) apyrase activity enabling hydrolyzation of ATP and ADP into AMP [27,28,33]. The binding of ATP to purinergic receptors activates the purinergic signaling pathway, which is stimulated by the infection.…”

“…Indeed, the expression of CD39 is an indicator of T-cell exhaustion as well and might be a potent biomarker for the prognostication of COVID-19 severity [20,21]. All in all, however, the data on CD39 expression in the context of COVID-19 are relatively sparse, and there are no studies simultaneously investigating the purinergic signaling pathway, as well as a broader panel of ICPMs in COVID-19 patients in order to find independent prognostic biomarkers under the exclusion of other confounding laboratory and clinical parameters [22][23][24][25][26][27][28][29][30].…”

Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review

“…MSCs may display a range of surface molecules and cellular cytokines according to where they originated from. CD45, CD34, CD19, CD14, CD11b, CD79, and HLA‐DR are not expressed, making CD90, CD73, and CD105 the most common markers that identify MSCs 95–98 . Several studies show that MSCs may be new way to treat DFU by improving angiogenesis and re‐epithelialization, helping to control the immune system, reducing inflammatory processes, and repairing DFU 17 …”

“…CD45, CD34, CD19, CD14, CD11b, CD79, and HLA‐DR are not expressed, making CD90, CD73, and CD105 the most common markers that identify MSCs. 95 , 96 , 97 , 98 Several studies show that MSCs may be new way to treat DFU by improving angiogenesis and re‐epithelialization, helping to control the immune system, reducing inflammatory processes, and repairing DFU. 17 …”

Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19

“…There is evidence to suggest that changes in the expression levels and frequencies of CD39 and CD73 in leucocytic cells have an impact on the immunopathology of viral illnesses such as viral hepatitis, cytomegalovirus (CMV), and HIV [19][20][21][22]. Regarding SARS-CoV-2 infection, the levels of inflammatory cytokines and purinergic signaling pathways are altered in patients with COVID-19 [23].…”