Alterations of redox and iron metabolism accompany the development of HIV latency

Shytaj et al., The EMBO Journal, 2020 asked why some HIV-infected cells die during productive infection while others survive to become the latent reservoir that antiretroviral therapy cannot clear. The answer they build is metabolic. Cells that survive replication turn up their antioxidant defences and, with them, the iron import pathway, a coupling the authors show both in cultured cells and in macaques infected with simian immunodeficiency virus. Those changes remodel promyelocytic leukemia protein nuclear bodies, a marker of latency: during productive infection the protein is degraded, and normal numbers of the bodies return once the cell transitions to latency or once oxidative stress or iron content is lowered.

AUM material appears in one supporting experiment. To test whether the protein restricts the virus rather than merely tracking it, the authors silenced PML in primary human CD4+ T cells using AUMsilence sdASOs, three different oligonucleotides against the transcript plus a control oligonucleotide, added drop wise into the cell suspension at 1 μM or 5 μM. No transfection reagent is named anywhere in the methods, which matters because these are primary human T cells.

The authors report the result with its limitation attached. Full silencing was not achieved in the primary cells, and only those oligonucleotides that did produce partial depletion of PML were associated with a higher proportion of p24 positive T cells in the culture. Read carefully, that is a dose-consistent result pointing the same way as the rest of the paper, and it is also an incomplete knockdown that the authors decline to overstate. The remainder of the study, including the macaque data and the iron chelation work, used no AUM material.