Proteomics

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Alterations of redox and iron metabolism accompany development of HIV latency


ABSTRACT: Metabolic alterations, such as oxidative stress, are hallmarks of HIV-1 infection. However, their influenceon the development of viral latency, and thus on HIV-1 persistence during antiretroviral therapy (ART),have just begun to be explored. We analyzed omics profiles ofin-vitroandin-vivomodels of infection byHIV-1 and its simian homolog SIVmac. We found that cells survive retroviral replication by upregulatingantioxidant pathways and intertwined iron import pathways. These changes are associated withremodeling of the redox sensitive promyelocytic leukemia protein nuclear bodies (PML NBs), an importantconstituent of nuclear architecture and a marker of HIV-1 latency. We found that PML is depleted inproductively infected cells and restored by ART. Moreover, we identified intracellular iron as a key linkbetween oxidative stress and PML depletion, thus supporting iron metabolism modulators aspharmacological tools to impair latency establishment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Christian Frese  

LAB HEAD: Marina Lusic

PROVIDER: PXD012907 | Pride | 2020-03-03

REPOSITORIES: Pride

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Publications


HIV-1 persists in a latent form during antiretroviral therapy, mainly in CD4<sup>+</sup> T cells, thus hampering efforts for a cure. HIV-1 infection is accompanied by metabolic alterations, such as oxidative stress, but the effect of cellular antioxidant responses on viral replication and latency is unknown. Here, we show that cells survive retroviral replication, both in vitro and in vivo in SIVmac-infected macaques, by upregulating antioxidant pathways and the intertwined iron import pathway.  ...[more]

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