New mitochondrial DNA synthesis enables NLRP3 inflammasome activation

Nature, Год журнала: 2018, Номер 560(7717), С. 198 - 203

Опубликована: Июль 24, 2018

Язык: Английский

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Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Дек. 6, 2018

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps the cycle, some also act as innate sensors triggering responses against infections. Accumulating evidence suggests an additional role for in promoting antiviral immunity combat viruses. Here, we review recent progress our understanding on how factors, particularly APOBEC3G, SAMHD1, Tetherin, TRIM5α have cell-autonomous potential induce resistance HIV-1 while adaptive immune responses. Also, provide overview these may connect with protein degradation pathways modulate anti-HIV-1 responses, summarize factors-based therapeutics. This brings global perspective influence restrictions intrinsic, innate, opening up novel research avenues therapeutic strategies fields drug discovery, gene therapy, vaccines control

Язык: Английский

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Monogenic Lupus: A Developing Paradigm of Disease

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Окт. 30, 2018

Monogenic lupus is a form of systemic erythematosus (SLE) that occurs in patients with single gene defect. This rare variant generally presents early onset severe disease, especially affecting the kidneys and central nervous system. To date, significant number genes have been implicated monogenic lupus, providing valuable insights into very complex disease process. Throughout this review, we will summarize reported to be associated or lupus-like diseases, pathogenic mechanisms affected by mutations involved upon inducing autoimmunity.

Язык: Английский

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Nucleases Acting at Stalled Forks: How to Reboot the Replication Program with a Few Shortcuts

Annual Review of Genetics, Год журнала: 2017, Номер 51(1), С. 477 - 499

Опубликована: Ноя. 27, 2017

In a lifetime, human being synthesizes approximately 2×10 16 meters of DNA, distance that corresponds to 130,000 times the between Earth and Sun. This daunting task is executed by thousands replication forks, which progress along chromosomes frequently stall when they encounter DNA lesions, unusual structures, RNA polymerases, or tightly-bound protein complexes. To complete synthesis before onset mitosis, eukaryotic cells have evolved complex mechanisms process restart arrested forks through coordinated action multiple nucleases, topoisomerases, helicases. this review, we discuss recent advances in understanding role regulation nucleases acting at stalled with focus on nucleolytic degradation nascent commonly referred as fork resection. We also effects deregulated resection genomic instability unscheduled activation interferon response under stress conditions.

Язык: Английский

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Restriction by SAMHD1 Limits cGAS/STING-Dependent Innate and Adaptive Immune Responses to HIV-1

Cell Reports, Год журнала: 2016, Номер 16(6), С. 1492 - 1501

Опубликована: Июль 29, 2016

SAMHD1 is a restriction factor for HIV-1 infection. mutations cause the autoinflammatory Aicardi-Goutières syndrome that characterized by chronic type I interferon (IFN) secretion. We show spontaneous IFN response in SAMHD1-deficient cells and mice requires cGAS/STING cytosolic DNA-sensing pathway. provide genetic evidence cell-autonomous control of lentivirus infection myeloid limits virus-induced production IFNs induction co-stimulatory markers. This program cell activation required reverse transcription, cGAS STING, signaling through receptor. Furthermore, reduced virus-specific cytotoxic T vivo. Therefore, virus magnitude responses. demonstrates competition between subsequent innate adaptive immune responses, concept with important implications treatment

Язык: Английский

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SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

Virology, Год журнала: 2016, Номер 495, С. 92 - 100

Опубликована: Май 13, 2016

Язык: Английский

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Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism

Nature Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Май 28, 2024

Язык: Английский

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Juvenile-onset systemic lupus erythematosus (jSLE) – Pathophysiological concepts and treatment options

Best Practice & Research Clinical Rheumatology, Год журнала: 2017, Номер 31(4), С. 488 - 504

Опубликована: Авг. 1, 2017

Язык: Английский

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A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Viruses, Год журнала: 2017, Номер 9(5), С. 125 - 125

Опубликована: Май 22, 2017

Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins episomal minichromosome, cccDNA acts template for new RNAs, ensuring formation progeny virions. Hence, represents the persistence reservoir that not directly targeted by current anti-HBV therapeutics. Eliminating will thus be heart cure chronic B. The low production most experimental models and associated problems reliable quantitation have long hampered deeper understanding molecular biology. Recent advancements including cccDNA-dependent cell culture systems begun identify select host repair enzymes usurps conversion. While this list bound grow, it may represent just one facet broader interaction damage response (DDR), network pathways sense aberrant structures process profoundly affect cycle, up inducing death if fails. Given divergent interactions between other viruses DDR intriguing see how copes multipronged system.

Язык: Английский

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CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Июль 10, 2018

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells an vitro model of quiescent CD4 T cells. Here we show that stimulation CD4+ with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression the activation markers HLA-DR CD69. HIV-1 infection increases expression. 79.2% CD32+/CD4+ from HIV+ individuals under antiretroviral treatment were HLA-DR+. Resting infected generally results higher integration provirus. We observe no difference provirus or replication-competent inducible latent CD32+ CD32- individuals. Our demonstrate expression is a marker cell raises questions regarding immune resting status harboring proviruses.

Язык: Английский

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