HIV-1 Vpr Functions in Primary CD4+ T Cells

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 420 - 420

Published: March 9, 2024

HIV-1 encodes four accesory proteins in addition to its structural and regulatory genes. Uniquely amongst them, Vpr is abundantly present within virions, meaning it poised exert various biological effects on the host cell upon delivery. In this way, contributes towards establishment of a successful infection, as evidenced by extent which depends factor achieve full pathogenicity vivo. Although HIV infects types organism, CD4+ T cells are preferentially targeted since they highly permissive productive concomitantly bringing about hallmark immune dysfunction that accompanies spread. The last several decades have seen unprecedented progress unraveling activities possesses at molecular scale, increasingly underscoring importance viral component. Nevertheless, remains controversial whether some these advances bear vivo relevance, commonly employed cellular models significantly differ from primary lymphocytes. One prominent example “established” ability induce G2 cycle arrest, with enigmatic physiological relevance infected objective review discoveries their context illustrate mechanisms whereby supports infection cells, whilst identifying findings require validation physiologically relevant models.

Language: Английский

---

Unintegrated HIV-1 DNAs are loaded with core and linker histones and transcriptionally silenced

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(47), P. 23735 - 23742

Published: Nov. 4, 2019

Significance Retroviruses are characterized by the reverse transcription of viral RNA genome into DNA and integration that to form provirus. However, little is known about nature unintegrated HIV-1 DNAs early upon delivery nucleus. Using chromatin immunoprecipitation assays, we found both core H1 linker histones deposited onto DNAs. We also confirmed transcriptional silencing determined presence posttranslational histone modifications characteristic inactive chromatin. Our results will help increase efficiency expression from nonintegrating HIV-1–based vectors after transient transfections with DNA.

Language: Английский

---

HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS–STING-mediated NF-κB signalling

Nature Microbiology, Journal Year: 2019, Volume and Issue: 4(12), P. 2552 - 2564

Published: Oct. 28, 2019

Language: Английский

---

DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

The human silencing hub (HUSH) complex binds to transcripts of LINE-1 retrotransposons (L1s) and other genomic repeats, recruiting MORC2 effectors remodel chromatin. How HUSH operate alongside DNA methylation, a central epigenetic regulator repeat transcription, remains largely unknown. Here we interrogate this relationship in neural progenitor cells (hNPCs), somatic model brain development that tolerates removal methyltransferase DNMT1. Upon loss or subunit TASOR hNPCs, L1s remain silenced by robust promoter methylation. However, genome demethylation activation evolutionarily-young attracts binding, simultaneous depletion DNMT1 causes massive accumulation L1 transcripts. We identify the same mechanistic hierarchy at pericentromeric α-satellites clustered protocadherin genes, repetitive elements important for chromosome structure neurodevelopment respectively. Our data delineate control repeats cells, with implications understanding vital functions HUSH-MORC2 hypomethylated contexts throughout development.

Language: Английский

---

IL-15 regulates susceptibility of CD4⁺T cells to HIV infection

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(41)

Published: Sept. 26, 2018

HIV integrates into the host genome to create a persistent viral reservoir. Stimulation of CD4+ memory T lymphocytes with common γc-chain cytokines renders these cells more susceptible infection, making them key component reservoir itself. IL-15 is up-regulated during primary time when established. Therefore, we investigated molecular and cellular impact on T-cell infection. We found that stimulation induces SAM domain HD domain-containing protein 1 (SAMHD1) phosphorylation due cell cycle entry, relieving an early block Perturbation pathways downstream receptor (IL-15R) indicated SAMHD1 after JAK dependent. Treating Ruxolitinib, inhibitor JAK1 JAK2, effectively blocked IL-15-induced protected from Using high-resolution single-cell immune profiling using mass cytometry by TOF (CyTOF), altered composition populations increasing proliferation cells, including stem (TSCM). IL-15-stimulated TSCM, harboring phosphorylated SAMHD1, were preferentially infected. propose plays pivotal role in creating self-renewing, facilitating infection cell-like properties. Time-limited interventions inhibitors, such as should prevent inactivation endogenous restriction factor protect this long-lived T-memory population

Language: Английский

---