HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?

In HIV disease, CD38 expression and its catalytic activity are increased in several cell types. This may lower intracelular NAD levels in CD4 T cells, shifting their metabolism and compromising mitochondria. CD38's products may increase cytoplasmic Ca²⁺. These effects may reduce CD4 T cell viability and regeneration capacity.

Despite abundant evidence associating CD38 overexpression and CD4 T cell depletion in HIV infection, no causal relation has been investigated. To address this issue, a series of mechanisms are proposed, supported by evidence from different fields, by which CD38 overexpression can facilitate CD4 T cell depletion in HIV infection. According to this model, increased catalytic activity of CD38 may reduce CD4 T cells' cytoplasmic nicotin‐amide adenine dinucleotide (NAD), leading to a chronic Warburg effect. This will reduce mitochondrial function. Simultaneously, CD38's catalytic products ADPR and cADPR may be transported to the cytoplasm, where they can activate calcium channels and increase cytoplasmic Ca²⁺ concentrations, further altering mitochondrial integrity. These mechanisms will decrease the viability and regenerative capacity of CD4 T cells. These hypotheses can be tested experimentally, and might reveal novel therapeutic targets. Also see the video abstract here https://youtu.be/k1LTyiTKPKs.

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