Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents

The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for...

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Bibliographic Details
Published in:Microorganisms (Basel) 2020-09, Vol.8 (10), p.1505
Main Authors: Campos Coelho, Antonio Victor, Moura, Ronald Rodrigues de, Crovella, Sergio
Format: Article
Language:English
Subjects:
Antiretroviral drugs
antiretroviral therapy
CD4 antigen
Cell activation
Cell differentiation
Depletion
Gene expression
Generalized linear models
Genes
Genomes
Guanine nucleotide-binding protein
HIV
Human immunodeficiency virus
Hypotheses
Immune response
Immune system
Infections
Kinases
Latency
Lymphocytes
Lymphocytes T
MAP kinase
Ontology
Protein kinase
reservoir
Review
RNA-Seq
shock-and-kill
Software
T cell receptors
Transcriptomes
transcriptomics
Viruses
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Summary:The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for latency reversal agents (LRAs). We hypothesize that if common molecular pathways elicited by the presence of LRAs are known, perhaps new, more efficient, “shock-and-kill” strategies can be found. Thus, the objective of the present study is to re-evaluate RNA-Seq assays to find differentially expressed genes (DEGs) during latency reversal via transcriptome analysis. We selected six studies (45 samples altogether: 16 negative controls and 29 LRA-treated CD4+ T cells) and 11 LRA strategies through a systematic search in Gene Expression Omnibus (GEO) and PubMed databases. The raw reads were trimmed, counted, and normalized. Next, we detected consistent DEGs in these independent experiments. AZD5582, romidepsin, and suberanilohydroxamic acid (SAHA) were the LRAs that modulated most genes. We detected 948 DEGs shared by those three LRAs. Gene ontology analysis and cross-referencing with other sources of the literature showed enrichment of cell activation, differentiation and signaling, especially mitogen-activated protein kinase (MAPK) and Rho-GTPases pathways.
ISSN:2076-2607
2076-2607
DOI:10.3390/microorganisms8101505