Ontology highlight
ABSTRACT:
PROVIDER: PRJNA433660 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6703650_1.fastq.gz | Fastqsanger.gz | |||
| SRR6703650_2.fastq.gz | Fastqsanger.gz | |||
| SRR6703651_1.fastq.gz | Fastqsanger.gz | |||
| SRR6703651_2.fastq.gz | Fastqsanger.gz | |||
| SRR6703652_1.fastq.gz | Fastqsanger.gz |
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Project description:HIV-1 viral core transport to the nucleus, an early infection event, triggers cleavage and polyadenylation specificity factor (CPSF)5 and CPSF6 to translocate from paraspeckles to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3’-untranslated regions (3’-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection–induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by changes in cellular function. Using two independent methodologies to assess APA in human primary CD4+ T cells and cell lines, we found that HIV-1 infection regulates APA, dependent on the interaction of CPSF6 with the viral capsid, recapitulating the APA phenotype observed in CPSF6 knockout cells. Our study demonstrates that HIV-1 infection leverages the interaction between the viral capsid and CPSF6 to co-opt cellular processes, alter gene expression, and drive pathogenesis.
2025-12-10 | GSE313109 | GEO
Project description:Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short FG peptides to isolated capsid hexamers have been characterized, how these proteins engage biologically relevant extended HIV-1 capsid lattices is unknown. We have identified that prion-like low complexity regions (LCR) enable avid binding of CPSF6, NUP153 and SEC24C to curved hexameric capsid lattices. Structural studies reveal that LCR-LCR interactions mediate multivalent CPSF6 assembly, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. CPSF6 LCR mediated avid binding to HIV-1 cores is essential for functional virus-host interactions in infected cells. Investigational drug lenacapavir can access unoccupied hydrophobic pockets in the CPSF6-HIV-1 complex and potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results elucidate previously undescribed mechanisms of virus-host interactions and potent inhibition of HIV-1.
2022-08-31 | PXD030332 | Pride
Project description:Wild type HIV-1 can infect macrophages to establish productive infection without triggering innate immune receptors or type 1 interferon responses that would otherwise restrict virus propagation. We found that HIV-1 capsid mutants that disrupt capsid interactions with two host factors CPSF6 and cyclophillin A do not replicate in macrophages because they do trigger interferon responses. Genome-wide transcriptional profiling was used to compare the repertoire of interferon stimulated genes induced by these capsid mutants after 24Êh with stimulation of macrophages with interferon-beta or with the RNA analogue Poly IC.
2014-02-12 | E-MTAB-1437 | biostudies-arrayexpress
Project description:Illumina sequencing data used in HIV-CRISPR screen with an ISG-specific sgRNA library (PIKAHIV) to find genes that block infection by the N74D and P90A HIV-1 capsid mutant viruses in THP-1 monocytic cells. For more information on the library and approach see Ohainle et al. eLife 2018 (PMID: 30520725). All screens performed here were done in a clonal ZAP-KO cell line (ZAP may inhibit the HIV-CRISPR vector used in the screen). Here we screen the Cyclophilin A-binding deficient mutant P90A and the CPSF6-binding deficient mutant N74D together with a wild type HIV-1 virus. The N74D screen was performed both with IFN treatment and without. These two HIV-1 capsid mutant viruses are hypersensitive to the effects of IFN.
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Project description:Cyclophilin A and CPSF6 regulate HIV-1 integration
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Project description:Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cGAS is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.
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Project description:HIV-1 integration sites were determined in wild-type HEK293T cells and cells lacking SET2D or MLL1. These experiments were performed to test the role of SET2D and MLL1 in LEDGF/p75-dependent HIV-1 integration site selection. Integration libraries were prepared by ligation-mediated PCR and sequenced on Illumina NextSeq 2000 for 150 bp paired-end sequencing.
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Project description:LGMDD2 is a rare form of muscular dystrophy characterized by a heterozygous deletion within the TNPO3 gen, firstly reported in a large Spanish family in 2001. TNPO3-wildtype is involved in the nuclear import of the essential splicing factors, a function altered in the mutated protein. Our group has shown that both TNPO3-wildtype and TNPO3-mutated proteins are translated in these patients. Besides its role in LGMDD2 disease, TNPO3 is also a HIV-1 co-factor but the mechanism underlying its antiviral action is still controversial. In an attempt to connect both LGMDD2 disease and HIV-1 infection, we demonstrated that PBMCs from LGMDD2 patients are refractory to in vitro HIV-1 infection due to a deficient viral integration subsequent to a deficient transport of the splicing factor CPSF6, due to TNPO3 mutation. The accumulation of HIV-1 capsid and retrotranscribed DNA in the cytosol may trigger anti-HIV inflammatory responses, therefore enhancing the blockade of HIV-1 replication. Further characterization of the crosstalk between HIV-1 infection and LGMDD2 disease may contribute to a better understanding of cellular alterations occurring in subjects living with LGMDD2. To this regard, here we show a high-throughput transcriptome profiling of PBMCs from LGMDD2 patients compared to their non-affected relatives. The differentially expressed genes were up-regulated and included G protein-coupled receptor binding chemokines, zinc ion binding proteins and metalloendopeptidases. The functional annotation showed an enrichment in immune response and inflammation pathways including IL-17, TNF, NOD-like receptor, TLR receptor, and NF-κβ signaling pathways, which are also known to be altered during HIV-1 infection. In summary, a holistic perspective of cellular changes occurring during LGMDD2 pathology is shown here providing new factors in this muscular dystrophy that may be considered in the design of new therapeutic strategies.
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