Distinct transcriptomic profiles of naïve CD4+ T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection

Petkov, Stefan; Chiodi, Francesca

doi:10.1016/j.ygeno.2021.08.014

Cited by 7 publications

(5 citation statements)

References 63 publications

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“…We investigated whole transcriptome data or total RNA-Seq studies. Sequence datasets were obtained from the GenBank data libraries 1 under accession number PRJNA724934 (Petkov and Chiodi, 2021). Thirty-nine RNA-seq datasets in FASTQ format were downloaded using the dataset sample experiment.…”

Section: Data Selectionmentioning

confidence: 99%

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Farsiu,

Ghorbani,

Karbanowicz

et al. 2024

Acta Virol.

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Long non-coding RNAs (lncRNAs) have gained prominence due to their involvement in various cellular processes, but their specific roles remain elusive. Dysregulation of lncRNAs has been implicated in the pathogenesis of several diseases. In this study, we aimed to shed light on the role of lncRNAs in individuals infected with human immunodeficiency virus type 1 (HIV-1) by examining their changes in the expression patterns related to the initiation of antiretroviral therapy (ART) during acute or chronic phases of infection, compared to healthy controls. We found 316 differentially expressed (DE) lncRNAs in patients receiving long-term ART, shedding light on their potential roles. We also observed interactions between these DE lncRNAs and specific microRNAs (miRNAs). Some of these miRNAs, such as hsa-miR-574-5p, hsa-miR-765, hsa-miR-6165, hsa-miR-1207-5p, and hsa-miR-378i, are associated with cancer progression or suppression, while others, including hsa-miR-328-5p, hsa-miR-4753-3p, and MiR-664, play roles in immune system regulation. Furthermore, our study revealed substantial enrichment in distinct Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as axon guidance, PI3K-Akt signaling, and MAPK signaling pathways. Although our results indicate possible molecular processes impacted by the discovered lncRNAs, we cannot explicitly establish causality or specific connections between lncRNAs and genes in these pathways, fostering more specific studies. Furthermore, Gene Ontology (GO) analysis highlighted terms such as cytoskeletal protein binding, ion channel function, synaptic processes, neuron projection, and the somatodendritic compartment, underscoring the relevance of lncRNAs in these cellular components within the context of HIV-1 infection and ART treatment. In conclusion, our study emphasizes the need for further exploration of lncRNAs as potential biomarkers and therapeutic targets in HIV-1-infected patients, with a particular focus on CD4+ T cells. Understanding the functions of lncRNAs in these contexts may pave the way for novel treatment strategies and improved patient outcomes, aligning with the broader goals of our research.

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Section: Data Selectionmentioning

confidence: 99%

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Farsiu,

Ghorbani,

Karbanowicz

et al. 2024

Acta Virol.

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“…To assess the network connectivity between HPV-human interacting proteins and either Hi-SIFs or HIV-human interacting proteins, we performed an integrative network propagation analysis. For our initial seed set, we used 26 Hi-SIFs extracted from the literature 31,[34][35][36] and previously reported AP-MSgenerated HIV 38 and HPV 37 preys. We used Pathway Commons as base network, subsetted for Reactome functional interactions (FI), CORUM, and physical interactions (Table S9, ESI †), we performed diffused (heat) kernel network propagation to capture the local topology of the interaction network.…”

Section: Network Propagationmentioning

confidence: 99%

“…Specifically, we used a network modeling approach called network propagation, which uses a ''guilt-by-association'' approach to propagate signal through a network to identify interconnected neighborhood clusters or pathways. 33 We separately performed network propagation of (i) Hi-SIFs known to be persistently over-expressed by HIV patients even when on ART relative to HIVunexposed individuals, 31,[34][35][36] (ii) human proteins (''preys'') previously reported to physically interact with HPV (HPVhuman PPIs), or (iii) HIV-human PPIs. 37,38 We then integrated the HPV propagation outputs with those of either the Hi-SIF or HIV to study host pathways that converged between HIV and HPV.…”

Section: Introductionmentioning

confidence: 99%

Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer

et al. 2023

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“…For example, one prior study compared gene expression among HIV “controllers” (individuals able to control virus in the absence of therapy) versus “non-controllers” [ 29 ]. Another study compared HIV non-controllers initiating ART “early” (<6 months from HIV infection) versus “later” (≥6 months after infection) [ 30 ]. However, no epidemiologic study has examined quantitative measures of the HIV reservoir size in relation to differences in host gene expression.…”

Section: Introductionmentioning

confidence: 99%

A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size

Dwivedi,

Gornalusse,

Siegel

et al. 2023

PLoS Pathog

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The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells from 191 ART-suppressed people with HIV (PWH). After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1, both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel (KCNJ2, GJB2), inflammasome (IL1A, CSF3, TNFAIP5, TNFAIP6, TNFAIP9, CXCL3, CXCL10), and innate immunity (TLR7) genes (FDR-adjusted q<0.05). Gene set enrichment analyses further identified significant associations of HIV usRNA with TLR4/microbial translocation (q = 0.006), IL-1/NRLP3 inflammasome (q = 0.008), and IL-10 (q = 0.037) signaling. Protein validation assays using ELISA and multiplex cytokine assays supported these observed inverse host gene correlations, with P3H3, IL-10, and TNF-α protein associations achieving statistical significance (p<0.05). Plasma IL-10 was also significantly inversely associated with HIV DNA (p = 0.016). HIV intact DNA was not associated with differential host gene expression, although this may have been due to a large number of undetectable values in our study. To our knowledge, this is the largest host transcriptomic study of the HIV reservoir. Our findings suggest that host gene expression may vary in response to the transcriptionally active reservoir and that changes in cellular proliferation genes may influence the size of the HIV reservoir. These findings add important data to the limited host genetic HIV reservoir studies to date.

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Distinct transcriptomic profiles of naïve CD4+ T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection

Cited by 7 publications

References 63 publications

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer

A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size

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