Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

Chang, Hsiang Chun; Bayeva, Marina; Taiwo, Babafemi; Palella, Frank J.; Hope, Thomas J.; Ardehali, Hossein

doi:10.1089/aid.2014.0169

Cited by 46 publications

(38 citation statements)

References 56 publications

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“…In line with this hypothesis, long‐term incubation with low concentrations (Fig EV4K) of the iron chelator deferiprone (L1) increased mortality of HIV‐1‐infected, but not mock‐infected cells (Fig EV4L). Previous studies have demonstrated that iron can increase HIV‐1 replication (Chang et al , ), likely by enhancing viral transcription (Debebe et al , ; Xu et al , ) or reverse transcription (van Asbeck et al , ; Traoré & Meyer, ). Indeed, administration of nontoxic concentrations (Fig EV4K) of the iron donor ferric nitriloacetate (Fe‐NTA) was associated with increased frequency of HIV‐1 gag p24 + cells (Fig F), which was more pronounced when the initial percentage of p24 + cells was higher (Fig F).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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HIV-1 persists in a latent form during antiretroviral therapy, mainly in CD4 + 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 SIVmacinfected macaques, by upregulating antioxidant pathways and the intertwined iron import pathway. These changes are associated with remodeling of promyelocytic leukemia protein nuclear bodies (PML NBs), an important constituent of nuclear architecture and a marker of HIV-1 latency. We found that PML NBs are hyper-SUMOylated and that PML protein is degraded via the ubiquitinproteasome pathway in productively infected cells, before latency establishment and after reactivation. Conversely, normal numbers of PML NBs were restored upon transition to latency or by decreasing oxidative stress or iron content. Our results highlight antioxidant and iron import pathways as determinants of HIV-1 latency and support their pharmacologic inhibition as tools to regulate PML stability and impair latency establishment.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…However, this biophysical observation requires validation to show anti-viral activity. The reported toxicity of iron(II) cylinders for mammalian cancer cell lines 24 and ability of iron(II) to promote HIV infection 29 , 30 , limits the potential application of this compound.…”

Section: Introductionmentioning

confidence: 99%

Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo

Cardo

Nawroth

Cail

et al. 2018

Sci Rep

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Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity with limited evidence of cellular cytotoxicity. These metallo-supramolecular compounds provide an exciting avenue for developing a new class of anti-viral agents.

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“…Serotransferrins are iron-binding proteins that have antimicrobial properties [20]. Higher iron levels in serum was associated with HIV replication and increased HIV infection [21]. Iron status was not an indication of disease severity in HIV-infected pregnant women in Malwai [22], but another nding was just reverse on iron overload was the severity in adults with HIV-1 infected Caucasian population [23].…”

Section: Discussionmentioning

confidence: 99%

Identification and differential expression of serotransferrin and apolipoprotein A-I in the plasma of HIV-1 patients treated with first-line antiretroviral therapy

Barik¹,

Mohanty

Mohanty³

et al. 2020

Preprint

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Background As plasma proteins were involved in drug metabolism, the aim of the study was to identify and characterize the plasma proteins of the drug resistant and drug respondent groups of HIV-1 infected first line ART patients with > 6 years in therapy. Methods Plasma proteomics analysis of the four drug-resistant (treatment failure) and four drug respondent (treatment responder) groups were conducted. High abundant plasma proteins like albumin and globulin were depleted from plasma through Aurum serum mini kit (Bio-Rad, USA). Plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Eight protein spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein database using the internal mascot search engine. Gene ontology study was completed through STRING v.11 and Panther 15.0. Results Out of eight spots from 2D gel of drug respondent and drug resistant samples analyzed by MALDI TOF/TOF, two proteins were found to have significant score (i;e > 56) after Flex analysis. These two proteins were identified to be apolipoproteinA1 and Serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. ApolipoproteinA1and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. Conclusion Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.

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Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

Cited by 46 publications

References 56 publications

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

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

Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo

Identification and differential expression of serotransferrin and apolipoprotein A-I in the plasma of HIV-1 patients treated with first-line antiretroviral therapy

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