HIV-1 in the latent reservoir is largely sensitive to circulating T cells

Warren, Joanna; Zhou, Shuntai; Xu, Yinyan; Moeser, Matthew; Kuruc, JoAnn; Gay, Cindy; Archin, Nancie M.; Swanstrom, Ronald; Goonetilleke, Nilu

doi:10.1016/s2055-6640(20)30188-6

Cited by 3 publications

(4 citation statements)

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“…We next investigated whether the HIV-1 genes gag, pol, and nef, which are reported to encode the most immunogenic viral proteins (49,50), are differentially selected within TN and memory CD4+ T-cell subsets, as this may provide more information as to the selection pressures on these cells. We identified intact ORFs for gag, pol, and nef within each proviral sequence (Supplementary Table 3).…”

Section: The Hiv-1 Proviral Landscape May Change Over Time Within Tn ...mentioning

confidence: 99%

“…In addition, each epitope was considered in the analysis only if the HLA-type of the corresponding participant was coincident with the HLA restriction for the identified epitope. The same analysis was performed for Nef sequences, since Nef has been reported as one of the most immunogenic HIV-1 proteins, along with Gag and Pol (49,50). We quantified the proportion of wild type epitopes, escape variants, and unrecognizable epitopes across the TN and memory CD4+ T-cell subsets for Gag, Pol, and Nef sequences (Supplementary Figure 3).…”

Section: The Proportion Of Sequences Harboring Recognizable Ctl Epito...mentioning

confidence: 99%

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The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

Duette¹,

Hiener²,

Morgan³

et al. 2022

Journal of Clinical Investigation

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Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4 + T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4 + T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4 + T cells when compared with naive, central, and transitional memory CD4 + T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.

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Section: The Hiv-1 Proviral Landscape May Change Over Time Within Tn ...mentioning

confidence: 99%

Section: The Proportion Of Sequences Harboring Recognizable Ctl Epito...mentioning

confidence: 99%

The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

Duette¹,

Hiener²,

Morgan³

et al. 2022

Journal of Clinical Investigation

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“…HBV and HPV integrations accumulate in genes that influence various cellular functions in addition to proliferation [18,20,22,27,[31][32][33][34][35], with recent studies implicating immune evasion through integration site-driven overexpression of T cell inhibitory ligands [34,35]. HIV-1 is the subject of intense cytotoxic T lymphocyte (CTL) pressure, which persists to a degree on ART [36,37] and, although many proviruses are latent in individuals treated with ART, some expression continues [38]. Ex vivo studies of in vivo infected human CD4 + T cells provide evidence that some HIV-1 reservoir cells may resist CD8 + CTL-mediated elimination Significance Integration of HIV-1 into the DNA of CD4 + T cells can alter cellular gene expression, but the contribution of this mechanism to the clonal expansion and persistence of HIV-1-infected cells remains unclear.…”

Section: Clonal Expansion Of the Hiv-1 Reservoir And The Roles Of Pro...mentioning

confidence: 99%

Potential multi-modal effects of provirus integration on HIV-1 persistence: lessons from other viruses

Linden

Jones

2022

Trends in Immunology

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“…ART has transformed HIV-1 from a fatal disease to a chronic disease [ 4 ]. But the persistence of HIV in potentially infected cells is a major obstacle to treatment [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

IFI27 is a potential therapeutic target for HIV infection

Huang¹,

Huang³

et al. 2022

Annals of Medicine

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Background Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health. Methods Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA. Results We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells. Conclusion The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.

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HIV-1 in the latent reservoir is largely sensitive to circulating T cells

Cited by 3 publications

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The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

Potential multi-modal effects of provirus integration on HIV-1 persistence: lessons from other viruses

IFI27 is a potential therapeutic target for HIV infection

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