Human immunodeficiency virus 1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA399117 | ENA |
REPOSITORIES: ENA
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Project description:Vertebrate genomes exhibit marked CG-suppression, that is lower than expected numbers of 5’-CG-3’ dinucleotides1. This feature is likely due to C-to-T mutations that have accumulated over hundreds of millions of years, driven by CG-specific DNA methyl transferases and spontaneous methyl-cytosine deamination. Remarkably, many RNA viruses of vertebrates that are not substrates for DNA methyl transferases mimic the CG-suppression of their hosts2-4. This striking property of viral genomes is unexplained4-6. In a synonymous mutagenesis experiment, we found that CG-suppression is essential for HIV-1 replication. The deleterious effect of CG dinucleotides on HIV-1 replication was cumulative, evident as cytoplasmic RNA depletion, and exerted by CG dinucleotides in both translated and non-translated exonic RNA sequences. A focused siRNA screen revealed that zinc finger antiviral protein (ZAP)7 inhibited virion production by cells infected with CG-enriched HIV-1. Crucially, HIV-1 mutants containing segments whose CG-content mimicked random sequence were defective in unmanipulated cells, but replicated normally in ZAP-deficient cells. Crosslinking-immunoprecipitation-sequencing assays demonstrated that ZAP binds directly and selectively to RNA sequences containing CG dinucleotides. These findings suggest that ZAP exploits host CG-suppression to discriminate non-self RNA. The dinucleotide composition of HIV-1, and perhaps other RNA viruses, appears to have adapted to evade this host defense.
2017-08-22 | GSE102843 | GEO
Project description:Infection of animal cells by many viruses is detected and countered by a variety of means, including recognition of non-self nucleic acids. The zinc-finger antiviral protein (ZAP) depletes cytoplasmic RNA that is recognized as foreign in mammalian cells by virtue of its elevated CG dinucleotide content compared to endogenous mRNAs. Here, we determined a crystal structure of a protein-RNA complex containing the N-terminal, four-zinc finger human (h) ZAP RNA binding domain (RBD), and a CG dinucleotide-containing RNA target. The structure reveals in molecular detail how hZAP is able to bind selectively to CG-rich RNA. Specifically, the four zinc fingers create a basic patch on the hZAP RBD surface. The highly basic second zinc finger contains a pocket that selectively accommodates CG dinucleotide bases. Structure guided mutagenesis, crosslinking-immunoprecipitation-sequencing assays, and RNA affinity assays show that the structurally defined CG-binding pocket is not required for RNA binding per se in human cells. However, the pocket is a crucial determinant of high affinity specific binding to CG-dinucleotide-containing RNA. Moreover, variations in the RNA binding specificity a panel of CG-binding pocket mutants quantitatively predict their selective antiviral activity against a CG-enriched HIV-1 strain. Overall, the hZAP RBD:RNA structure provides an atomic-level explanation for how ZAP selectively targets foreign, CG-rich RNA.
2019-11-01 | GSE139667 | GEO
Project description:Human immunodeficiency virus 1 Antiviral Resistance NGS-Sanger
| PRJNA486832 | ENA
Project description:Using genome-wide RNA-seq to compare immunoprofiles of human sertoli cells, we show that the most prominent response to ZIKV at early stage of infection was suppression of cell growth and proliferation functional pathways. Peak virus replication was associated with induction of multiple antiviral defense pathways. Unique ZIKV-associated signatures included dysregulation of germ cell-Sertoli cell junction signaling.
2023-06-20 | GSE235210 | GEO
Project description:Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonises several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is largely unknown. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, the long (ZAP-L) and short (ZAP-S), is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP decelerates the progression of HCMV infection. SLAM-sequencing revealed that ZAP restricts HCMV at early stages of infection by destabilising a distinct subset of viral transcripts with low CG content. In summary, this report provides evidence of an important antiviral role for ZAP in host defense against HCMV infection and highlights its differentiated function during DNA virus infection.
2021-04-22 | PXD023559 | Pride
Project description:HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP
| PRJDB9077 | ENA
Project description:DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpC and CpT dinucleotides. Here we report a comprehensive analysis of non-CG methylation in 72 genome-scale DNA methylation maps across human pluripotent and differentiated cell types. We confirm non-CG methylation to be predominant in pluripotent cell types and observe an expected decrease upon differentiation and near complete absence in various differentiated cells. Our data highlight that non-CG methylation is highly variable and shows little conservation between different pluripotent cell lines. While we show a strong correlation of non-CG methylation and DNMT3 expression levels we find a statistical independence of non-CG methylation from pluripotency associated gene expression. Finally, non-CG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of DNA methylation in human cells and help clarify previous observations using a large representative sample set. Examination of nonCG DNA methylation patterns in pluripotent and differentiated cells
2011-08-31 | E-GEOD-27432 | biostudies-arrayexpress
Project description:Targeting FBXO44 or SUV39H1 transcriptionally reactivates repetitive elements, triggering RIG-I-MDA5-MAVS and cGAS-STING antiviral defense responses and IFN signaling, specifically in cancer cells
2021-03-26 | GSE139974 | GEO
Project description:Dynamic SUMO modifications of diverse cellular protein groups are critical to orchestrate resolution of stresses such as genome damage, hypoxia or proteotoxicity. Defense against pathogen insult (usually reliant upon host recognition of ‘non-self’ nucleic acids), is also modulated by SUMO, but the underlying mechanisms are incompletely understood. Here, we used quantitative SILAC-based proteomics to survey pan-viral host SUMOylation responses, creating a resource of almost 600 common and unique SUMO remodeling events that are mounted during influenza A and B virus infections, as well as during viral immune stimulation. By integrating knock-out/reconstitution models and transcriptomics, we provide evidence that influenza virus triggered loss of SUMO-modified TRIM28 leads to derepression of endogenous retroviral elements, unmasking this cellular pool of ‘self’ double-stranded (ds) RNA. Consequently, loss of SUMO-modified TRIM28 potentiates canonical cytosolic dsRNA-activated interferon-mediated defenses. Our data suggest that a key nuclear mechanism that prevents expression of endogenous retroviruses has been functionally co-opted via a stress-induced SUMO switch to augment antiviral immunity.
2019-08-12 | PXD014136 | Pride
Project description:CD47 is an ubiquitously expressed surface molecule that has a significant impact on immune responses. However, its role for antiviral immunity is not fully understood. We can show that CD47 has an inhibitory role in influenza virus defense, since CD47-deficient mice (CD47-/-) display an increased viral clearance during influenza virus infection. This effect is strongly associated with alveolar macrophages, yet the underlying mechanisms are unclear. Thus, to assess the precise impact of CD47 on antiviral action of alveolar macrophages, transcriptional analysis of ex vivo isolated alveolar macrophages from CD47-/- and WT mice were performed isolated 3dpi. Surprisingly, instead of classical antiviral mediators, an increased expression of both hemoglobin α and hemoglobin β was found in CD47 deficient compared to WT alveolar macrophages upon influenza A virus infection. Importantly, antiviral activity of hemoglobin was already shown for other viruses and thus, CD47 might limit influenza virus defense via the regulation of hemoglobin, which could act as a modulator of the antiviral immune response during the infection.
2022-12-09 | GSE201825 | GEO