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| Status |
Public on Jan 30, 2020 |
| Title |
Alterations of redox and iron metabolism accompany development of HIV latency |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Metabolic alterations, such as oxidative stress, are hallmarks of HIV-1 infection. However, their influence on 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 of in-vitro and in-vivo models of infection by HIV-1 and its simian homolog SIVmac. We found that cells survive retroviral replication by upregulating antioxidant pathways and intertwined iron import pathways. These changes are associated with remodeling of the redox sensitive promyelocytic leukemia protein nuclear bodies (PML NBs), an important constituent of nuclear architecture and a marker of HIV-1 latency. We found that PML is depleted in productively infected cells and restored by ART. Moreover, we identified intracellular iron as a key link between oxidative stress and PML depletion, thus supporting iron metabolism modulators as pharmacological tools to impair latency establishment.
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| Overall design |
Primary CD4+ T-cells were isolated from total blood of three healthy donors (designated as donor 14, donor 49 and donor 50). After isolation CD4+ T-cells were activated for 72 hours by adding the Dynabeads® Human T-Activator CD3/CD28 using a bead/cell ratio of 1:2. Following activation cells were divided in two groups and either infected with HIV-1 NL4-3 (2ng p24/million cells) or mock infected. Cells were cultured in RPMI 1640 supplemented with 20% fetal bovine serum (FBS), penicillin/streptomycin, and 10 ng/mL IL-2 and kept at a concentration between 1-2 million cells/mL. Cell pellets were collected at 3-7-9 and 14 days post-infection and used for total RNA extraction and subsequent library construction and RNA-Seq analysis.
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| Contributor(s) |
Shytaj IL, Lucic B, Forcato M, Bicciato S, Lusic M |
| Citation(s) |
32157726 |
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| Submission date |
Feb 28, 2019 |
| Last update date |
Apr 30, 2020 |
| Contact name |
Silvio Bicciato |
| E-mail(s) |
silvio.bicciato@unipd.it
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| Phone |
+39-049-827-6108
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| Organization name |
University of Padova
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| Department |
Molecular Medicine
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| Street address |
via U. Bassi 59/b
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| City |
Padova |
| ZIP/Postal code |
35131 |
| Country |
Italy |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA524856 |
| SRA |
SRP187079 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127468_ExpressionMatrix_counts.xlsx |
6.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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